Modified-release topical hydrogels: a ten-year review

  • Fernanda Machado Croisfelt
  • Louise Lacalendola Tundisi
  • Janaína Artem AtaideEmail author
  • Edgar Silveira
  • Elias Basile Tambourgi
  • Angela Faustino Jozala
  • Eliana Maria Barbosa Souto
  • Priscila Gava Mazzola


Hydrogels are polymeric networks with tridimensional structure, which are able to load water and other substances. Such property makes hydrogels suitable for innumerous applications in biomedical field. Hydrogels are being used as raw materials in pharmaceutical formulations for more than 60 years, while significant progress is very well documented in topical use. Natural and synthetic polymers have been applied to develop smart hydrogels that respond to physiological stimuli to follow the release of the loaded bioactive ingredient. This paper discusses the most relevant polymers commonly used in pharmaceutical formulations for modified topical delivery.



Authors acknowledge FAPESP (process number 2016/03444-5), CNPq and CAPES for the financial support.


  1. 1.
    Dadsetan M, Liu Z, Pumberger M et al (2010) A stimuli-responsive hydrogel for doxorubicin delivery. Biomaterials 31:8051–8062. CrossRefGoogle Scholar
  2. 2.
    Wichterle O, LÍM D (1960) Hydrophilic gels for biological use. Nature 185:117–118. CrossRefGoogle Scholar
  3. 3.
    Buwalda SJ, Boere KW, Dijkstra PJ, Feijen J, Vermonden T, Hennink WE (2014) Hydrogels in a historical perspective: from simple networks to smart materials. J Control Release Off J Control Release Soc 190:254–273. CrossRefGoogle Scholar
  4. 4.
    Nalbandian RM, Henry RL, Wilks HS (1972) Artificial skin. II. Pluronic F-127 silver nitrate or silver lactate gel in the treatment of thermal burns. J Biomed Mater Res 6:583–590. CrossRefGoogle Scholar
  5. 5.
    Lim F, Sun AM (1980) Microencapsulated islets as bioartificial endocrine pancreas. Science 210:908–910CrossRefGoogle Scholar
  6. 6.
    Yannas IV, Lee E, Orgill D, Skrabut EM, Murphy GF (1989) Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. Proc Natl Acad Sci 86(3):933–937CrossRefGoogle Scholar
  7. 7.
    Jeong B, Bae YH, Lee DS, Kim SW (1997) Biodegradable block copolymers as injectable drug-delivery systems. Nature 388:860. CrossRefGoogle Scholar
  8. 8.
    Cascone MG, Sim B, Sandra D (1995) Blends of synthetic and natural polymers as drug delivery systems for growth hormone. Biomaterials 16:569–574. CrossRefGoogle Scholar
  9. 9.
    Davis BM, Normando EM, Guo L et al (2014) Topical delivery of Avastin to the posterior segment of the eye in vivo using annexin A5-associated liposomes. Small 10:1575–1584. CrossRefGoogle Scholar
  10. 10.
    Yahia LH, Chirani N, Gritsch L et al (2015) History and applications of hydrogels. J Biomedical Sci 4:2. CrossRefGoogle Scholar
  11. 11.
    Harrison IP, Spada F (2018) Hydrogels for atopic dermatitis and wound management: a superior drug delivery vehicle. Pharmaceutics 10:71. CrossRefGoogle Scholar
  12. 12.
    Ashley GW, Henise J, Reid R, Santi DV (2013) Hydrogel drug delivery system with predictable and tunable drug release and degradation rates. Proc Natl Acad Sci U S A 110:2318–2323. CrossRefGoogle Scholar
  13. 13.
    Saha S, Shivarajakumar R, Karri VVSR (2018) Pluronic lecithin organogels: an effective topical and transdermal drug delivery system. Int J Pharm Sci Res 11:4540–4550. CrossRefGoogle Scholar
  14. 14.
    Kathe K, Kathpalia H (2017) Film forming systems for topical and transdermal drug delivery. Asian J Pharm Sci 12:487–497. CrossRefGoogle Scholar
  15. 15.
    Aderibigbe BA, Buyana B (2018) Alginate in wound dressings. Pharmaceutics 10:42. CrossRefGoogle Scholar
  16. 16.
    Samchenko Y, Ulberg Z, Korotych O (2011) Multipurpose smart hydrogel systems. Adv Colloid Interface Sci 168:247–262. CrossRefGoogle Scholar
  17. 17.
    Deligkaris K, Tadele TS, Olthuis W, van den Berg A (2010) Hydrogel-based devices for biomedical applications. Sens Actuators B Chem 147:765–774. CrossRefGoogle Scholar
  18. 18.
    Hennink WE, van Nostrum CF (2012) Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev 64:223–236. CrossRefGoogle Scholar
  19. 19.
    da Silva R, Ganzarolli de Oliveira M (2007) Effect of the cross-linking degree on the morphology of poly(NIPAAm-co-AAc) hydrogels. Polymer 48:4114–4122. CrossRefGoogle Scholar
  20. 20.
    Ahmed EM (2015) Hydrogel: preparation, characterization, and applications: a review. J Adv Res 6:105–121. CrossRefGoogle Scholar
  21. 21.
    Tatiana A, Joana FF, Sajan J, Antonello S, Amelia MS, Eliana BS (2015) Hydrophilic polymers for modified-release nanoparticles: a review of mathematical modelling for pharmacokinetic analysis. Curr Pharm Des 21:3090–3096. CrossRefGoogle Scholar
  22. 22.
    Chai Q, Jiao Y, Yu X (2017) Hydrogels for biomedical applications: their characteristics and the mechanisms behind them. Gels 3:6CrossRefGoogle Scholar
  23. 23.
    Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 60:1638–1649. CrossRefGoogle Scholar
  24. 24.
    Martínez-Ruvalcaba A, Chornet E, Rodrigue D (2007) Viscoelastic properties of dispersed chitosan/xanthan hydrogels. Carbohydr Polym 67:586–595. CrossRefGoogle Scholar
  25. 25.
    Gyles DA, Castro LD, Silva JOC, Ribeiro-Costa RM (2017) A review of the designs and prominent biomedical advances of natural and synthetic hydrogel formulations. Eur Polym J 88:373–392. CrossRefGoogle Scholar
  26. 26.
    Tanan W, Panichpakdee J, Saengsuwan S (2019) Novel biodegradable hydrogel based on natural polymers: synthesis, characterization, swelling/reswelling and biodegradability. Eur Polym J 112:678–687. CrossRefGoogle Scholar
  27. 27.
    Xu X, Bai B, Ding C, Wang H, Suo Y (2015) Synthesis and properties of an ecofriendly superabsorbent composite by grafting the poly(acrylic acid) onto the surface of dopamine-coated sea buckthorn branches. Ind Eng Chem Res 54:3268–3278. CrossRefGoogle Scholar
  28. 28.
    Pan G, Guo Q, Ma Y, Yang H, Li B (2013) Thermo-responsive hydrogel layers imprinted with RGDS peptide: a system for harvesting cell sheets. Angew Chem (Int Ed Engl) 52:6907–6911. CrossRefGoogle Scholar
  29. 29.
    Koetting MC, Guido JF, Gupta M, Zhang A, Peppas NA (2016) pH-responsive and enzymatically-responsive hydrogel microparticles for the oral delivery of therapeutic proteins: effects of protein size, crosslinking density, and hydrogel degradation on protein delivery. J Control Release 221:18–25. CrossRefGoogle Scholar
  30. 30.
    Sionkowska A, Skopinska-Wisniewska J, Planecka A, Kozlowska J (2010) The influence of UV irradiation on the properties of chitosan films containing keratin. Polym Degrad Stab 95:2486–2491. CrossRefGoogle Scholar
  31. 31.
    Ciofani G, Raffa V, Pizzorusso T, Menciassi A, Dario P (2008) Characterization of an alginate-based drug delivery system for neurological applications. Med Eng Phys 30:848–855. CrossRefGoogle Scholar
  32. 32.
    Ataide JA, Cefali LC, Croisfelt FM, Zanchetta B, Souto EB, Nascimento LO, Mazzola PG (2018) Wound healing process and synthetic actives: a review. Skin Pharmacol Physiol 97(8):2892–2923Google Scholar
  33. 33.
    Horiguchi I, Sakai Y (2015) Alginate Encapsulation of Pluripotent Stem Cells Using a Co-axial Nozzle. J Vis Exp JoVE 101:e52835–e52835. CrossRefGoogle Scholar
  34. 34.
    Severino P, Chaud MV, Shimojo A et al (2015) Sodium alginate-cross-linked polymyxin B sulphate-loaded solid lipid nanoparticles: antibiotic resistance tests and HaCat and NIH/3T3 cell viability studies. Colloids Surf B 129:191–197. CrossRefGoogle Scholar
  35. 35.
    Li Y, Rodrigues J, Tomas H (2012) Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem Soc Rev 41:2193–2221. CrossRefGoogle Scholar
  36. 36.
    Chiu CT, Lee JS, Chu CS, Chang YP, Wang YJ (2008) Development of two alginate-based wound dressings. J Mater Sci: Mater Med 19:2503. CrossRefGoogle Scholar
  37. 37.
    Colinet I, Dulong V, Mocanu G, Picton L, Le Cerf D (2009) New amphiphilic and pH-sensitive hydrogel for controlled release of a model poorly water-soluble drug. Eur J Pharm Biopharm 73:345–350. CrossRefGoogle Scholar
  38. 38.
    Josef E, Zilberman M, Bianco-Peled H (2010) Composite alginate hydrogels: an innovative approach for the controlled release of hydrophobic drugs. Acta Biomater 6:4642–4649. CrossRefGoogle Scholar
  39. 39.
    Jain D, Carvalho E, Banerjee R (2010) Biodegradable hybrid polymeric membranes for ocular drug delivery. Acta Biomater 6:1370–1379. CrossRefGoogle Scholar
  40. 40.
    El-Hag Ali A, Abd El-Rehim HA, Kamal H, Hegazy DESA (2008) Synthesis of carboxymethyl cellulose based drug carrier hydrogel using ionizing radiation for possible use as site specific delivery system. J Macromol Sci Part A 45:628–634. CrossRefGoogle Scholar
  41. 41.
    Namazi H, Rakhshaei R, Hamishehkar H, Kafil HS (2016) Antibiotic loaded carboxymethylcellulose/MCM-41 nanocomposite hydrogel films as potential wound dressing. Int J Biol Macromol 85:327–334. CrossRefGoogle Scholar
  42. 42.
    Ma J, Xu Y, Fan B, Liang B (2007) Preparation and characterization of sodium carboxymethylcellulose/poly(N-isopropylacrylamide)/clay semi-IPN nanocomposite hydrogels. Eur Polym J 43:2221–2228. CrossRefGoogle Scholar
  43. 43.
    Capanema NSV, Mansur AAP, Carvalho SM et al (2018) Bioengineered carboxymethyl cellulose-doxorubicin prodrug hydrogels for topical chemotherapy of melanoma skin cancer. Carbohydr Polym 195:401–412. CrossRefGoogle Scholar
  44. 44.
    Muñoz G, Valencia C, Valderruten N, Ruiz-Durántez E, Zuluaga F (2015) Extraction of chitosan from Aspergillus niger mycelium and synthesis of hydrogels for controlled release of betahistine. React Funct Polym 91–92:1–10. CrossRefGoogle Scholar
  45. 45.
    Solé I, Vílchez S, Miras J, Montanyà N, García-Celma MJ, Esquena J (2017) DHA and l-carnitine loaded chitosan hydrogels as delivery systems for topical applications. Colloids Surf A 525:85–92. CrossRefGoogle Scholar
  46. 46.
    Dash M, Chiellini F, Ottenbrite RM, Chiellini E (2011) Chitosan—A versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci 36:981–1014. CrossRefGoogle Scholar
  47. 47.
    Jose S, Prema MT, Chacko AJ, Thomas AC, Souto EB (2011) Colon specific chitosan microspheres for chronotherapy of chronic stable angina. Colloids Surf B 83:277–283. CrossRefGoogle Scholar
  48. 48.
    Jose S, Fangueiro JF, Smitha J et al (2012) Cross-linked chitosan microspheres for oral delivery of insulin: taguchi design and in vivo testing. Colloids Surf B 92:175–179. CrossRefGoogle Scholar
  49. 49.
    Severino P, de Oliveira GGG, Ferraz HG, Souto EB, Santana MHA (2012) Preparation of gastro-resistant pellets containing chitosan microspheres for improvement of oral didanosine bioavailability. J Pharm Anal 2:188–192. CrossRefGoogle Scholar
  50. 50.
    Jose S, Fangueiro JF, Smitha J et al (2013) Predictive modeling of insulin release profile from cross-linked chitosan microspheres. Eur J Med Chem 60:249–253. CrossRefGoogle Scholar
  51. 51.
    Severino P, Da Silva CF, Dalla Costa TCT et al (2014) In vivo absorption of didanosine formulated in pellets composed of chitosan microspheres. Vivo 28:1045–1050Google Scholar
  52. 52.
    Severino P, da Silva CF, da Silva MA, Santana MHA, Souto EB (2016) Chitosan cross-linked pentasodium tripolyphosphate micro/nanoparticles produced by ionotropic gelation. Sugar Tech 18:49–54. CrossRefGoogle Scholar
  53. 53.
    Ferreira C, da Silva P, Severino F Martins, Santana MHA, Souto EB (2015) Didanosine-loaded chitosan microspheres optimized by surface-response methodology: a modified “maximum likelihood classification” approach formulation for reverse transcriptase inhibitors. Biomed Pharmacother 70:46–52. CrossRefGoogle Scholar
  54. 54.
    Severino P, Silva H, Souto EB, Santana MHA, Dalla Costa TCT (2012) Analysis of in vivo absorption of didanosine tablets in male adult dogs by HPLC. J Pharm Anal 2:29–34. CrossRefGoogle Scholar
  55. 55.
    Cardoso AM, de Oliveira EG, Coradini K et al (2019) Chitosan hydrogels containing nanoencapsulated phenytoin for cutaneous use: skin permeation/penetration and efficacy in wound healing. Mater Sci Eng C 96:205–217. CrossRefGoogle Scholar
  56. 56.
    Souto EB, Wissing SA, Barbosa CM, Müller RH (2004) Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations. Eur J Pharm Biopharm 58:83–90. CrossRefGoogle Scholar
  57. 57.
    Fan Q, Ma J, Xu Q et al (2015) Animal-derived natural products review: focus on novel modifications and applications. Colloids Surf B 128:181–190. CrossRefGoogle Scholar
  58. 58.
    Laffleur F (2017) Evaluation of chemical modified hydrogel formulation for topical suitability. Int J Biol Macromol. CrossRefGoogle Scholar
  59. 59.
    Barbosa GP, Debone HS, Severino P, Souto EB, da Silva CF (2016) Design and characterization of chitosan/zeolite composite films—Effect of zeolite type and zeolite dose on the film properties. Mater Sci Eng C 60:246–254. CrossRefGoogle Scholar
  60. 60.
    Kamoun EA, Chen X, Mohy Eldin MS, Kenawy E-RS (2015) Crosslinked poly(vinyl alcohol) hydrogels for wound dressing applications: a review of remarkably blended polymers. Arabian J Chem 8:1–14. CrossRefGoogle Scholar
  61. 61.
    Madaghiele M, Demitri C, Sannino A, Ambrosio L (2014) Polymeric hydrogels for burn wound care: advanced skin wound dressings and regenerative templates. Burns Trauma 2:153–161. CrossRefGoogle Scholar
  62. 62.
    Ribeiro MP, Espiga A, Silva D, Baptista P, Henriques J, Ferreira C (2009) Development of a new chitosan hydrogel for wound dressing. Wound Repair Regen 17:817–824. CrossRefGoogle Scholar
  63. 63.
    Jaiswal M, Gupta A, Agrawal AK, Jassal M, Dinda AK, Koul V (2013) Bi-layer composite dressing of gelatin nanofibrous mat and poly vinyl alcohol hydrogel for drug delivery and wound healing application: in-vitro and in-vivo studies. J Biomed Nanotechnol 9:1495–1508. CrossRefGoogle Scholar
  64. 64.
    Atiyeh BS, Costagliola M, Hayek SN, Dibo SA (2007) Effect of silver on burn wound infection control and healing: review of the literature. Burns J Int Soc Burn Inj 33:139–148. CrossRefGoogle Scholar
  65. 65.
    Morsi NM, Abdelbary GA, Ahmed MA (2014) Silver sulfadiazine based cubosome hydrogels for topical treatment of burns: development and in vitro/in vivo characterization. Eur J Pharm Biopharm 86:178–189. CrossRefGoogle Scholar
  66. 66.
    Jodar KSP, Balcao VM, Chaud MV et al (2015) Development and characterization of a hydrogel containing silver sulfadiazine for antimicrobial topical applications. J Pharm Sci 104:2241–2254. CrossRefGoogle Scholar
  67. 67.
    de Paula E, Cereda CM, Tofoli GR, Franz-Montan M, Fraceto LF, de Araujo DR (2010) Drug delivery systems for local anesthetics. Recent Pat Drug Deliv Formul 4:23–34CrossRefGoogle Scholar
  68. 68.
    Teixeira RS, Veiga FJB, Oliveira RS et al (2014) Effect of cyclodextrins and pH on the permeation of tetracaine: supramolecular assemblies and release behavior. Int J Pharm 466:349–358. CrossRefGoogle Scholar
  69. 69.
    Sun Y, Du L, Liu Y et al (2014) Transdermal delivery of the in situ hydrogels of curcumin and its inclusion complexes of hydroxypropyl-β-cyclodextrin for melanoma treatment. Int J Pharm 469:31–39. CrossRefGoogle Scholar
  70. 70.
    Thatiparti TR, von Recum HA (2010) Cyclodextrin complexation for affinity-based antibiotic delivery. Macromol Biosci 10:82–90. CrossRefGoogle Scholar
  71. 71.
    dos Santos JF, Alvarez-Lorenzo C, Silva M et al (2009) Soft contact lenses functionalized with pendant cyclodextrins for controlled drug delivery. Biomaterials 30:1348–1355. CrossRefGoogle Scholar
  72. 72.
    Vaishya RD, Khurana V, Patel S, Mitra AK (2014) Controlled ocular drug delivery with nanomicelles Wiley interdisciplinary reviews. Nanomed Nanobiotechnol 6:422–437. CrossRefGoogle Scholar
  73. 73.
    Loftsson T, Stefánsson E (2017) Cyclodextrins and topical drug delivery to the anterior and posterior segments of the eye. Int J Pharm 531:413–423. CrossRefGoogle Scholar
  74. 74.
    Sun G, Zhang X, Shen YI, Sebastian R, Dickinson LE, Fox-Talbot K (2011) Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proc Natl Acad Sci USA. CrossRefGoogle Scholar
  75. 75.
    Unnithan AR, Sasikala ARK, Murugesan P et al (2015) Electrospun polyurethane-dextran nanofiber mats loaded with Estradiol for post-menopausal wound dressing. Int J Biol Macromol 77:1–8. CrossRefGoogle Scholar
  76. 76.
    Ribeiro MP, Morgado PI, Miguel SP, Coutinho P, Correia IJ (2013) Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing. Mater Sci Eng C Mater Biol Appl. CrossRefGoogle Scholar
  77. 77.
    Cassano R, Trombino S, Muzzalupo R, Tavano L, Picci N (2009) A novel dextran hydrogel linking trans-ferulic acid for the stabilization and transdermal delivery of vitamin E. Eur J Pharm Biopharm 72:232–238. CrossRefGoogle Scholar
  78. 78.
    Kompella UB, Amrite AC, Pacha Ravi R, Durazo SA (2013) Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res 36:172–198. CrossRefGoogle Scholar
  79. 79.
    Fomina N, McFearin C, Sermsakdi M, Edigin O, Almutairi A (2010) UV and near-IR triggered release from polymeric nanoparticles. J Am Chem Soc 132:9540–9542. CrossRefGoogle Scholar
  80. 80.
    Campos EJ, Campos A, Martins J, Ambrósio AF (2017) Opening eyes to nanomedicine: where we are, challenges and expectations on nanotherapy for diabetic retinopathy. Nanomed Nanotechnol Biol Med 13:2101–2113. CrossRefGoogle Scholar
  81. 81.
    Akhtar MF, Hanif M, Ranjha NM (2016) Methods of synthesis of hydrogels—a review. Saudi Pharm J 24:554–559. CrossRefGoogle Scholar
  82. 82.
    Yu J, Xu X, Yao F et al (2014) In situ covalently cross-linked PEG hydrogel for ocular drug delivery applications. Int J Pharm 470:151–157. CrossRefGoogle Scholar
  83. 83.
    Andreani T, Souza ALRD, Kiill CP et al (2014) Preparation and characterization of PEG-coated silica nanoparticles for oral insulin delivery. Int J Pharm 473:627–635. CrossRefGoogle Scholar
  84. 84.
    Sánchez-López E, Egea MA, Cano A et al (2016) PEGylated PLGA nanospheres optimized by design of experiments for ocular administration of dexibuprofen—in vitro, ex vivo and in vivo characterization. Colloids Surf B 145:241–250. CrossRefGoogle Scholar
  85. 85.
    Lin CC, Anseth KS (2009) PEG hydrogels for the controlled release of biomolecules in regenerative medicine. Pharm Res 26:631–643. CrossRefGoogle Scholar
  86. 86.
    Gabriel D, Mugnier T, Courthion H et al (2016) Improved topical delivery of tacrolimus: a novel composite hydrogel formulation for the treatment of psoriasis. J Control Release 242:16–24. CrossRefGoogle Scholar
  87. 87.
    Rallis E, Korfitis C, Gregoriou S, Rigopoulos D (2007) Assigning new roles to topical tacrolimus. Expert Opin Investig Drugs 16:1267–1276. CrossRefGoogle Scholar
  88. 88.
    Korman N, Menter A, Elmets CA, Feldman SR, Gelfand JM, Gordon KB et al (2009) Guidelines of care for the management of psoriasis and psoriatic arthritis. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 60(4):643–659. CrossRefGoogle Scholar
  89. 89.
    Mabilleau G, Aguado E, Stancu IC, Cincu C, Baslé MF, Chappard D (2008) Effects of FGF-2 release from a hydrogel polymer on bone mass and microarchitecture. Biomaterials 29:1593–1600. CrossRefGoogle Scholar
  90. 90.
    Zeng N, Dumortier G, Maury M, Mignet N, Boudy V (2014) Influence of additives on a thermosensitive hydrogel for buccal delivery of salbutamol: relation between micellization, gelation, mechanic and release properties. Int J Pharm 467:70–83. CrossRefGoogle Scholar
  91. 91.
    Sivashanmugam A, Arun Kumar R, Vishnu Priya M, Nair SV, Jayakumar R (2015) An overview of injectable polymeric hydrogels for tissue engineering. Eur Polymer J 72:543–565. CrossRefGoogle Scholar
  92. 92.
    dos Santos JF, Couceiro R, Concheiro A, Torres-Labandeira JJ, Alvarez-Lorenzo C (2008) Poly(hydroxyethyl methacrylate-co-methacrylated-beta-cyclodextrin) hydrogels: synthesis, cytocompatibility, mechanical properties and drug loading/release properties. Acta Biomater 4:745–755. CrossRefGoogle Scholar
  93. 93.
    Venkatesh S, Sizemore SP, Byrne ME (2007) Biomimetic hydrogels for enhanced loading and extended release of ocular therapeutics. Biomaterials 28:717–724. CrossRefGoogle Scholar
  94. 94.
    Caló E, Khutoryanskiy VV (2015) Biomedical applications of hydrogels: a review of patents and commercial products. Eur Polymer J 65:252–267. CrossRefGoogle Scholar
  95. 95.
    Ali M, Horikawa S, Venkatesh S, Saha J, Hong JW, Byrne ME (2007) Zero-order therapeutic release from imprinted hydrogel contact lenses within in vitro physiological ocular tear flow. J Control Release 124:154–162. CrossRefGoogle Scholar
  96. 96.
    Xinming L, Yingde C, Lloyd AW et al (2008) Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: a review. Contact Lens Anterior Eye 31:57–64. CrossRefGoogle Scholar
  97. 97.
    Ciolino JB, Hoare TR, Iwata NG et al (2009) A drug-eluting contact lens. Invest Ophthalmol Vis Sci 50:3346–3352. CrossRefGoogle Scholar
  98. 98.
    Ciolino JB, Hudson SP, Mobbs AN et al (2011) A prototype antifungal contact lens. Invest Ophthalmol Vis Sci 52:6286–6291. CrossRefGoogle Scholar
  99. 99.
    Araújo J, Vega E, Lopes C, Egea MA, Garcia ML, Souto EB (2009) Effect of polymer viscosity on physicochemical properties and ocular tolerance of FB-loaded PLGA nanospheres. Colloids Surf B 72:48–56. CrossRefGoogle Scholar
  100. 100.
    Jose S, Sowmya S, Cinu TA, Aleykutty NA, Thomas S, Souto EB (2014) Surface modified PLGA nanoparticles for brain targeting of Bacoside-A. Eur J Pharm Sci 63:29–35. CrossRefGoogle Scholar
  101. 101.
    Abrego G, Alvarado H, Souto EB et al (2015) Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration. Eur J Pharm Biopharm 95:261–270. CrossRefGoogle Scholar
  102. 102.
    Cañadas C, Alvarado H, Calpena AC et al (2016) In vitro, ex vivo and in vivo characterization of PLGA nanoparticles loading pranoprofen for ocular administration. Int J Pharm 511:719–727. CrossRefGoogle Scholar
  103. 103.
    Sánchez-López E, Ettcheto M, Egea MA et al (2018) Memantine loaded PLGA PEGylated nanoparticles for Alzheimer’s disease: in vitro and in vivo characterization. J Nanobiotechnol 16:32. CrossRefGoogle Scholar
  104. 104.
    Schoubben A, Blasi P, Deluca PP (2012) Effect of agitation regimen on the in vitro release of leuprolide from poly(lactic-co-glycolic) acid microparticles. J Pharm Sci 101:1212–1220. CrossRefGoogle Scholar
  105. 105.
    Abrego G, Alvarado H, Souto EB et al (2016) Biopharmaceutical profile of hydrogels containing pranoprofen-loaded PLGA nanoparticles for skin administration: in vitro, ex vivo and in vivo characterization. Int J Pharm 501:350–361. CrossRefGoogle Scholar
  106. 106.
    Vega E, Egea MA, Garduno-Ramirez ML et al (2013) Flurbiprofen PLGA-PEG nanospheres: role of hydroxy-beta-cyclodextrin on ex vivo human skin permeation and in vivo topical anti-inflammatory efficacy. Colloids Surf B Biointerfaces 110:339–346. CrossRefGoogle Scholar
  107. 107.
    Terukina T, Naito Y, Tagami T et al (2016) The effect of the release behavior of simvastatin from different PLGA particles on bone regeneration in vitro and in vivo: comparison of simvastatin-loaded PLGA microspheres and nanospheres. J Drug Deliv Sci Technol 33:136–142. CrossRefGoogle Scholar
  108. 108.
    Makadia HK, Siegel SJ (2011) Poly lactic-co-glycolic acid (plga) as biodegradable controlled drug delivery carrier. Polymers 3:1377–1397. CrossRefGoogle Scholar
  109. 109.
    Gao Y, Ren F, Ding B et al (2011) A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel. J Drug Target 19:516–527. CrossRefGoogle Scholar
  110. 110.
    Yan Q, Xiao L-Q, Tan L et al (2015) Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics. J Biomed Mater Res Part A 103:3580–3589. CrossRefGoogle Scholar
  111. 111.
    Liang F, Jonette AW, Li SK, Gaurav T, Jinsong H, Daniel IC (2014) Assessment of PLGA-PEG-PLGA copolymer hydrogel for sustained drug delivery in the ear. Curr Drug Deliv 11:279–286. CrossRefGoogle Scholar
  112. 112.
    Chen Y-S, Tsou P-C, Lo J-M, Tsai H-C, Wang Y-Z, Hsiue G-H (2013) Poly(N-isopropylacrylamide) hydrogels with interpenetrating multiwalled carbon nanotubes for cell sheet engineering. Biomaterials 34:7328–7334. CrossRefGoogle Scholar
  113. 113.
    Alexander A, Ajazuddin J Khan, Saraf S, Saraf S (2014) Polyethylene glycol (PEG)–Poly(N-isopropylacrylamide) (PNIPAAm) based thermosensitive injectable hydrogels for biomedical applications. Eur J Pharm Biopharm 88:575–585. CrossRefGoogle Scholar
  114. 114.
    Kulkarni RV, Mangond BS, Mutalik S, Sa B (2011) Interpenetrating polymer network microcapsules of gellan gum and egg albumin entrapped with diltiazem–resin complex for controlled release application. Carbohydr Polym 83:1001–1007. CrossRefGoogle Scholar
  115. 115.
    Y-t Kim J-M, Caldwell RV Bellamkonda (2009) Nanoparticle-mediated local delivery of methylprednisolone after spinal cord injury. Biomaterials 30:2582–2590. CrossRefGoogle Scholar
  116. 116.
    García-Uriostegui L, Burillo G, Bucio E (2012) Synthesis and characterization of thermosensitive interpenetrating polymer networks based on N-isopropylacrylamide/N-acryloxysuccinimide, crosslinked with polylysine, grafted onto polypropylene. Radiat Phys Chem 81:295–300. CrossRefGoogle Scholar
  117. 117.
    de Sousa A, Maria DA, de Sousa RG, de Sousa EMB (2010) Synthesis and characterization of mesoporous silica/poly(N-isopropylacrylamide) functional hybrid useful for drug delivery. J Mater Sci 45:1478–1486. CrossRefGoogle Scholar
  118. 118.
    D’Cruz OJ, Uckun FM (2014) Vaginal microbicides and their delivery platforms. Expert Opin Drug Deliv 11:723–740. CrossRefGoogle Scholar
  119. 119.
    Li C, Han C, Zhu Y, Lu W, Li Q, Liu Y (2014) In vivo evaluation of an in-situ hydrogel system for vaginal administration. Pharmazie 69:458–460Google Scholar
  120. 120.
    Priya James H, John R, Alex A, Anoop KR (2014) Smart polymers for the controlled delivery of drugs – a concise overview. Acta Pharm Sin B 4:120–127. CrossRefGoogle Scholar
  121. 121.
    Jiang S, Liu S, Feng W (2011) PVA hydrogel properties for biomedical application. J Mech Behav Biomed Mater 4:1228–1233. CrossRefGoogle Scholar
  122. 122.
    Coviello T, Matricardi P, Marianecci C, Alhaique F (2007) Polysaccharide hydrogels for modified release formulations. J Control Release 119:5–24. CrossRefGoogle Scholar
  123. 123.
    Singh B, Pal L (2012) Sterculia crosslinked PVA and PVA-poly(AAm) hydrogel wound dressings for slow drug delivery: mechanical, mucoadhesive, biocompatible and permeability properties. J Mech Behav Biomed Mater 9:9–21. CrossRefGoogle Scholar
  124. 124.
    Lipsky BA, Hoey C (2009) Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis Off Publ Infect Dis Soc Am 49:1541–1549. CrossRefGoogle Scholar
  125. 125.
    Yasasvini S, Anusa RS, VedhaHari BN, Prabhu PC, RamyaDevi D (2017) Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity. Mater Sci Eng C 72:160–167. CrossRefGoogle Scholar
  126. 126.
    Paolicelli P, Varani G, Pacelli S et al (2017) Design and characterization of a biocompatible physical hydrogel based on scleroglucan for topical drug delivery. Carbohydr Polym 174:960–969. CrossRefGoogle Scholar
  127. 127.
    Lapasin R, Abrami M, Grassi M, Šebenik U (2017) Rheology of laponite-scleroglucan hydrogels. Carbohydr Polym 168:290–300. CrossRefGoogle Scholar
  128. 128.
    Grassi M, Lapasin R, Coviello T, Matricardi P, Di Meo C, Alhaique F (2009) Scleroglucan/borax/drug hydrogels: structure characterisation by means of rheological and diffusion experiments. Carbohydr Polym 78:377–383. CrossRefGoogle Scholar
  129. 129.
    Viñarta SC, Delgado OD, Figueroa LIC, Fariña JI (2013) Effects of thermal, alkaline and ultrasonic treatments on scleroglucan stability and flow behavior. Carbohydr Polym 94:496–504. CrossRefGoogle Scholar
  130. 130.
    Cerreto A, Corrente F, Botta B et al (2013) NMR characterization of carboxymethyl scleroglucan. Int J Polym Anal Charact 18:587–595. CrossRefGoogle Scholar
  131. 131.
    Corrente F, Matricardi P, Paolicelli P, Tita B, Vitali F, Casadei MA (2009) Physical carboxymethylscleroglucan/calciumion hydrogels as modified drug delivery systems in topical formulations. Molecules 14:2684–2698. CrossRefGoogle Scholar
  132. 132.
    Corrente F, Paolicelli P, Matricardi P, Tita B, Vitali F, Casadei MA (2012) Novel pH-sensitive physical hydrogels of carboxymethyl scleroglucan. J Pharm Sci 101:256–267. CrossRefGoogle Scholar
  133. 133.
    Ruskowitz ER, Comerford MP, Badeau BA, DeForest CA (2019) Logical stimuli-triggered delivery of small molecules from hydrogel biomaterials. Biomater Sci 7:542–546. CrossRefGoogle Scholar
  134. 134.
    Li X, Su X (2018) Multifunctional smart hydrogels: potential in tissue engineering and cancer therapy. J Mater Chem B 6:4714–4730. CrossRefGoogle Scholar
  135. 135.
    Sood N, Bhardwaj A, Mehta S, Mehta A (2016) Stimuli-responsive hydrogels in drug delivery and tissue engineering. Drug Deliv 23:748–770. CrossRefGoogle Scholar
  136. 136.
    Zhao H, Xu K, Zhu P, Wang C, Chi Q (2019) Smart hydrogels with high tunability of stiffness as a biomimetic cell carrier. Cell Biol Int 43:84–97. CrossRefGoogle Scholar
  137. 137.
    Giuliano E, Paolino D, Fresta M, Cosco D (2018) Mucosal applications of poloxamer 407-based hydrogels: an overview. Pharmaceutics. CrossRefGoogle Scholar
  138. 138.
    Yang R, Sabharwal V, Okonkwo OS et al (2016) Treatment of otitis media by transtympanic delivery of antibiotics. Sci Transl Med 8:356ra120. CrossRefGoogle Scholar
  139. 139.
    Das D, Pham HTT, Lee S, Noh I (2019) Fabrication of alginate-based stimuli-responsive, non-cytotoxic, terpolymeric semi-IPN hydrogel as a carrier for controlled release of bovine albumin serum and 5-amino salicylic acid. Mater Sci Eng C 98:42–53. CrossRefGoogle Scholar
  140. 140.
    LeValley PJ, Tibbitt MW, Noren B et al (2019) Immunofunctional photodegradable poly(ethylene glycol) hydrogel surfaces for the capture and release of rare cells. Colloids Surf B 174:483–492. CrossRefGoogle Scholar
  141. 141.
    Wang Y (2018) Programmable hydrogels. Biomaterials. CrossRefGoogle Scholar
  142. 142.
    Croisfelt F, Martins BC, Rescolino R et al (2015) Poly(N-Isopropylacrylamide)-co-acrylamide hydrogels for the controlled release of bromelain from agroindustrial residues of Ananas comosus. Planta Med. CrossRefGoogle Scholar
  143. 143.
    Croisfelt FM, Ataide JA, Tundisi LL et al (2018) Characterization of PNIPAAm-co-AAm hydrogels for modified release of bromelain. Eur Polym J 105:48–54. CrossRefGoogle Scholar
  144. 144.
    Ishii Y, Nakae T, Sakamoto F et al (2008) A transcutaneous vaccination system using a hydrogel patch for viral and bacterial infection. J Control Release 131:113–120. CrossRefGoogle Scholar
  145. 145.
    Chen C-C, Fang C-L, Al-Suwayeh SA, Leu Y-L, Fang J-Y (2011) Transdermal delivery of selegiline from alginate–pluronic composite thermogels. Int J Pharm 415:119–128. CrossRefGoogle Scholar
  146. 146.
    Szabó B, Kállai N, Tóth G, Hetényi G, Zelkó R (2014) Drug release profiles and microstructural characterization of cast and freeze dried vitamin B12 buccal films by positron annihilation lifetime spectroscopy. J Pharm Biomed Anal 89:83–87. CrossRefGoogle Scholar
  147. 147.
    Shiohira H, Fujii M, Koizumi N, Kondoh M, Watanabe Y (2009) Novel chronotherapeutic rectal aminophylline delivery system for therapy of asthma. Int J Pharm 379:119–124. CrossRefGoogle Scholar
  148. 148.
    Rezvanian M, Ahmad N, Mohd Amin MCI, Ng S-F (2017) Optimization, characterization, and in vitro assessment of alginate-pectin ionic cross-linked hydrogel film for wound dressing applications. Int J Biol Macromol 97:131–140. CrossRefGoogle Scholar
  149. 149.
    Fetih G (2010) Meloxicam formulations for transdermal delivery: hydrogels versus organogels. J Drug Deliv Sci Technol 20:451–456. CrossRefGoogle Scholar
  150. 150.
    Das A, Kumar A, Patil NB, Viswanathan C, Ghosh D (2015) Preparation and characterization of silver nanoparticle loaded amorphous hydrogel of carboxymethylcellulose for infected wounds. Carbohydr Polym 130:254–261. CrossRefGoogle Scholar
  151. 151.
    Meher JG, Tarai M, Yadav NP, Patnaik A, Mishra P, Yadav KS (2013) Development and characterization of cellulose–polymethacrylate mucoadhesive film for buccal delivery of carvedilol. Carbohydr Polym 96:172–180. CrossRefGoogle Scholar
  152. 152.
    Sivashankari PR, Prabaharan M (2016) Prospects of chitosan-based scaffolds for growth factor release in tissue engineering. Int J Biol Macromol 93:1382–1389. CrossRefGoogle Scholar
  153. 153.
    Sajomsang W, Nuchuchua O, Saesoo S et al (2013) A comparison of spacer on water-soluble cyclodextrin grafted chitosan inclusion complex as carrier of eugenol to mucosae. Carbohydr Polym 92:321–327. CrossRefGoogle Scholar
  154. 154.
    Liu L, Gao Q, Lu X, Zhou H (2016) In situ forming hydrogels based on chitosan for drug delivery and tissue regeneration. Asian J Pharm Sci 11:673–683. CrossRefGoogle Scholar
  155. 155.
    Casettari L, Illum L (2014) Chitosan in nasal delivery systems for therapeutic drugs. J Control Release 190:189–200. CrossRefGoogle Scholar
  156. 156.
    Wu Y, Wu S, Hou L et al (2012) Novel thermal-sensitive hydrogel enhances both humoral and cell-mediated immune responses by intranasal vaccine delivery. Eur J Pharm Biopharm 81:486–497. CrossRefGoogle Scholar
  157. 157.
    Wu Y, Wei W, Zhou M et al (2012) Thermal-sensitive hydrogel as adjuvant-free vaccine delivery system for H5N1 intranasal immunization. Biomaterials 33:2351–2360. CrossRefGoogle Scholar
  158. 158.
    Xu J, Tam M, Samaei S et al (2017) Mucoadhesive chitosan hydrogels as rectal drug delivery vessels to treat ulcerative colitis. Acta Biomater 48:247–257. CrossRefGoogle Scholar
  159. 159.
    Zhu Y, Hoshi R, Chen S et al (2016) Sustained release of stromal cell derived factor-1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes. J Control Release 238:114–122. CrossRefGoogle Scholar
  160. 160.
    Yar M, Shahzadi L, Mehmood A et al (2017) Deoxy-sugar releasing biodegradable hydrogels promote angiogenesis and stimulate wound healing. Mater Today Commun 13:295–305. CrossRefGoogle Scholar
  161. 161.
    Ciobanu BC, Cadinoiu AN, Popa M, Desbrières J, Peptu CA (2014) Modulated release from liposomes entrapped in chitosan/gelatin hydrogels. Mater Sci Eng C 43:383–391. CrossRefGoogle Scholar
  162. 162.
    Cheng Y-H, Hung K-H, Tsai T-H et al (2014) Sustained delivery of latanoprost by thermosensitive chitosan–gelatin-based hydrogel for controlling ocular hypertension. Acta Biomater 10:4360–4366. CrossRefGoogle Scholar
  163. 163.
    Tang Q, Luo C, Lu B et al (2017) Thermosensitive chitosan-based hydrogels releasing stromal cell derived factor-1 alpha recruit MSC for corneal epithelium regeneration. Acta Biomater 61:101–113. CrossRefGoogle Scholar
  164. 164.
    Xu J, Strandman S, Zhu JXX, Barralet J, Cerruti M (2015) Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery. Biomaterials 37:395–404. CrossRefGoogle Scholar
  165. 165.
    Casimiro MH, Gil MH, Leal JP (2007) Drug release assays from new chitosan/pHEMA membranes obtained by gamma irradiation. Nucl Instrum Methods Phys Res Sect B 265:406–409. CrossRefGoogle Scholar
  166. 166.
    Radhakumary C, Antonty M, Sreenivasan K (2011) Drug loaded thermoresponsive and cytocompatible chitosan based hydrogel as a potential wound dressing. Carbohydr Polym 83:705–713. CrossRefGoogle Scholar
  167. 167.
    Layek B, Rahman Nirzhor SS, Rathi S, Kandimalla KK, Wiedmann TS, Prabha S (2019) Design, development, and characterization of imiquimod-loaded chitosan films for topical delivery. AAPS Pharm Sci Tech 20:58. CrossRefGoogle Scholar
  168. 168.
    Hebeish A, Hashem M, El-Hady MMA, Sharaf S (2013) Development of CMC hydrogels loaded with silver nano-particles for medical applications. Carbohydr Polym 92:407–413. CrossRefGoogle Scholar
  169. 169.
    Lam YL, Muniyandy S, Kamaruddin H, Mansor A, Janarthanan P (2015) Radiation cross-linked carboxymethyl sago pulp hydrogels loaded with ciprofloxacin: influence of irradiation on gel fraction, entrapped drug and in vitro release. Radiat Phys Chem 106:213–222. CrossRefGoogle Scholar
  170. 170.
    Alibolandi M, Mohammadi M, Taghdisi SM, Abnous K, Ramezani M (2017) Synthesis and preparation of biodegradable hybrid dextran hydrogel incorporated with biodegradable curcumin nanomicelles for full thickness wound healing. Int J Pharm 532:466–477. CrossRefGoogle Scholar
  171. 171.
    Choi SG, Baek EJ, Davaa E et al (2013) Topical treatment of the buccal mucosa and wounded skin in rats with a triamcinolone acetonide-loaded hydrogel prepared using an electron beam. Int J Pharm 447:102–108. CrossRefGoogle Scholar
  172. 172.
    Luaces-Rodríguez A, Díaz-Tomé V, González-Barcia M et al (2017) Cysteamine polysaccharide hydrogels: study of extended ocular delivery and biopermanence time by PET imaging. Int J Pharm 528:714–722. CrossRefGoogle Scholar
  173. 173.
    Singh B, Sharma S, Dhiman A (2013) Design of antibiotic containing hydrogel wound dressings: biomedical properties and histological study of wound healing. Int J Pharm 457:82–91. CrossRefGoogle Scholar
  174. 174.
    Fiorica C, Palumbo FS, Pitarresi G, Bongiovì F, Giammona G (2017) Hyaluronic acid and beta cyclodextrins films for the release of corneal epithelial cells and dexamethasone. Carbohydr Polym 166:281–290. CrossRefGoogle Scholar
  175. 175.
    Chandrasekar MJN, Kumar SM, Manikandan D, Nanjan MJ (2011) Isolation and evaluation of a polysaccharide from Prunus amygdalus as a carrier for transbuccosal delivery of Losartan potassium. Int J Biol Macromol 48:773–778. CrossRefGoogle Scholar
  176. 176.
    de Santana DCAS, Pupo TT, Sauaia MG, da Silva RS, Lopez RFV (2010) Nitric oxide photorelease from hydrogels and from skin containing a nitro-ruthenium complex. Int J Pharm 391:21–28. CrossRefGoogle Scholar
  177. 177.
    Koop HS, de Freitas RA, de Souza MM, Savi-Jr R, Silveira JLM (2015) Topical curcumin-loaded hydrogels obtained using galactomannan from schizolobium parahybae and xanthan. Carbohydr Polym 116:229–236. CrossRefGoogle Scholar
  178. 178.
    Tan G, Yu S, Li J, Pan W (2017) Development and characterization of nanostructured lipid carriers based chitosan thermosensitive hydrogel for delivery of dexamethasone. Int J Biol Macromol 103:941–947. CrossRefGoogle Scholar
  179. 179.
    Hao J, Zhao J, Zhang S et al (2016) Fabrication of an ionic-sensitive in situ gel loaded with resveratrol nanosuspensions intended for direct nose-to-brain delivery. Colloids Surf B 147:376–386. CrossRefGoogle Scholar
  180. 180.
    Ribeiro A, Veiga F, Santos D, Torres-Labandeira JJ, Concheiro A, Alvarez-Lorenzo C (2012) Hydrophilic acrylic hydrogels with built-in or pendant cyclodextrins for delivery of anti-glaucoma drugs. Carbohydr Polym 88:977–985. CrossRefGoogle Scholar
  181. 181.
    Matsuo K, Ishii Y, Quan Y-S et al (2011) Transcutaneous vaccination using a hydrogel patch induces effective immune responses to tetanus and diphtheria toxoid in hairless rat. J Control Release 149:15–20. CrossRefGoogle Scholar
  182. 182.
    Van Hove AH, Burke K, Antonienko E, Brown E, Benoit DSW (2015) Enzymatically-responsive pro-angiogenic peptide-releasing poly(ethylene glycol) hydrogels promote vascularization in vivo. J Control Release 217:191–201. CrossRefGoogle Scholar
  183. 183.
    Anumolu SS, DeSantis AS, Menjoge AR et al (2010) Doxycycline loaded poly(ethylene glycol) hydrogels for healing vesicant-induced ocular wounds. Biomaterials 31:964–974. CrossRefGoogle Scholar
  184. 184.
    Rolim WR, Pieretti JC, Renó DLS et al (2019) Antimicrobial activity and cytotoxicity to tumor cells of nitric oxide donor and silver nanoparticles containing PVA/PEG films for topical applications. ACS Appl Mater Interfaces 11:6589–6604. CrossRefGoogle Scholar
  185. 185.
    Huang J, Wang W, Yu J et al (2017) Combination of dexamethasone and Avastin® by supramolecular hydrogel attenuates the inflammatory corneal neovascularization in rat alkali burn model. Colloids Surf B 159:241–250. CrossRefGoogle Scholar
  186. 186.
    Gong C, Wu Q, Wang Y et al (2013) A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials 34:6377–6387. CrossRefGoogle Scholar
  187. 187.
    García-Millán E, Koprivnik S, Otero-Espinar FJ (2015) Drug loading optimization and extended drug delivery of corticoids from pHEMA based soft contact lenses hydrogels via chemical and microstructural modifications. Int J Pharm 487:260–269. CrossRefGoogle Scholar
  188. 188.
    García-Millán E, Quintáns-Carballo M, Otero-Espinar FJ (2017) Improved release of triamcinolone acetonide from medicated soft contact lenses loaded with drug nanosuspensions. Int J Pharm 525:226–236. CrossRefGoogle Scholar
  189. 189.
    Kapoor Y, Dixon P, Sekar P, Chauhan A (2017) Incorporation of drug particles for extended release of cyclosporine a from poly-hydroxyethyl methacrylate hydrogels. Eur J Pharm Biopharm 120:73–79. CrossRefGoogle Scholar
  190. 190.
    Glisoni RJ, García-Fernández MJ, Pino M et al (2013) β-Cyclodextrin hydrogels for the ocular release of antibacterial thiosemicarbazones. Carbohydr Polym 93:449–457. CrossRefGoogle Scholar
  191. 191.
    dos Santos J-FR, Couceiro R, Concheiro A, Torres-Labandeira J-J, Alvarez-Lorenzo C (2008) Poly(hydroxyethyl methacrylate-co-methacrylated-β-cyclodextrin) hydrogels: synthesis, cytocompatibility, mechanical properties and drug loading/release properties. Acta Biomater 4:745–755. CrossRefGoogle Scholar
  192. 192.
    Maulvi FA, Lakdawala DH, Shaikh AA et al (2016) In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery. J Control Release 226:47–56. CrossRefGoogle Scholar
  193. 193.
    Hsu K-H, Fentzke RC, Chauhan A (2013) Feasibility of corneal drug delivery of cysteamine using vitamin E modified silicone hydrogel contact lenses. Eur J Pharm Biopharm 85:531–540. CrossRefGoogle Scholar
  194. 194.
    Santoveña A, Monzón C, Delgado A, Evora C, Llabrés M, Fariña JB (2017) Development of a standard method for in vitro evaluation of Triamcinolone and BMP-2 diffusion mechanism from thermosensitive and biocompatible composite hyaluronic acid-pluronic hydrogels. J Drug Deliv Sci Technol 42:284–291. CrossRefGoogle Scholar
  195. 195.
    Qian S, Wong YC, Zuo Z (2014) Development, characterization and application of in situ gel systems for intranasal delivery of tacrine. Int J Pharm 468:272–282. CrossRefGoogle Scholar
  196. 196.
    Jose S, Ansa CR, Cinu TA et al (2013) Thermo-sensitive gels containing lorazepam microspheres for intranasal brain targeting. Int J Pharm 441:516–526. CrossRefGoogle Scholar
  197. 197.
    Heilmann S, Küchler S, Wischke C, Lendlein A, Stein C, Schäfer-Korting M (2013) A thermosensitive morphine-containing hydrogel for the treatment of large-scale skin wounds. Int J Pharm 444:96–102. CrossRefGoogle Scholar
  198. 198.
    Pitt WG, Zhao Y, Jack DR, Nelson JL, Pruitt JD (2011) In vitro release of phospholipid from a silicone hydrogel contact lens. Contact Lens Anterior Eye 34:S15. CrossRefGoogle Scholar
  199. 199.
    Xiaobo W, Luis D, Rayne F, Qiang Y, Carl L, Fabrice P (2011) Principles of inner ear sustained release following intratympanic administration. Laryngosc 121:385–391. CrossRefGoogle Scholar
  200. 200.
    Yuan Y, Cui Y, Zhang L et al (2012) Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesulide. Int J Pharm 430:114–119. CrossRefGoogle Scholar
  201. 201.
    Karavasili C, Fatouros DG (2016) Smart materials: in situ gel-forming systems for nasal delivery. Drug Discov Today 21:157–166. CrossRefGoogle Scholar
  202. 202.
    Vigato AA, Querobino SM, de Faria NC et al (2019) Synthesis and characterization of nanostructured lipid-poloxamer organogels for enhanced skin local anesthesia. Eur J Pharm Sci 128:270–278. CrossRefGoogle Scholar
  203. 203.
    Liu X, Gan H, Hu C et al (2019) Silver sulfadiazine nanosuspension-loaded thermosensitive hydrogel as a topical antibacterial agent. Int J Nanomed 14:12Google Scholar
  204. 204.
    Fu Din O, Mustapha DW Kim et al (2015) Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. Eur J Pharm Biopharm 94:64–72. CrossRefGoogle Scholar
  205. 205.
    Zeng N, Mignet N, Dumortier G et al (2015) Poloxamer bioadhesive hydrogel for buccal drug delivery: cytotoxicity and trans-epithelial permeability evaluations using TR146 human buccal epithelial cell line. Int J Pharm 495:1028–1037. CrossRefGoogle Scholar
  206. 206.
    Zeng N, Seguin J, Destruel P-L et al (2017) Cyanine derivative as a suitable marker for thermosensitive in situ gelling delivery systems: in vitro and in vivo validation of a sustained buccal drug delivery. Int J Pharm 534:128–135. CrossRefGoogle Scholar
  207. 207.
    Huang W, Zhang N, Hua H et al (2016) Preparation, pharmacokinetics and pharmacodynamics of ophthalmic thermosensitive in situ hydrogel of betaxolol hydrochloride. Biomed Pharmacother 83:107–113. CrossRefGoogle Scholar
  208. 208.
    Donnelly RF, Cassidy CM, Loughlin RG et al (2009) Delivery of Methylene Blue and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate from cross-linked poly(vinyl alcohol) hydrogels: a potential means of photodynamic therapy of infected wounds. J Photochem Photobiol B 96:223–231. CrossRefGoogle Scholar
  209. 209.
    Zhou G, Ruhan A, Ge H et al (2014) Research on a novel poly (vinyl alcohol)/lysine/vanillin wound dressing: biocompatibility, bioactivity and antimicrobial activity. Burns 40:1668–1678. CrossRefGoogle Scholar
  210. 210.
    Morgado PI, Miguel SP, Correia IJ, Aguiar-Ricardo A (2017) Ibuprofen loaded PVA/chitosan membranes: a highly efficient strategy towards an improved skin wound healing. Carbohydr Polym 159:136–145. CrossRefGoogle Scholar
  211. 211.
    Gao B, Yang Q, Zhao X, Jin G, Ma Y, Xu F (2016) 4D bioprinting for biomedical applications. Trends Biotechnol 34:746–756. CrossRefGoogle Scholar
  212. 212.
    Ruskowitz ER, DeForest CA (2018) Photoresponsive biomaterials for targeted drug delivery and 4D cell culture. Nat Rev Mater 3:17087. CrossRefGoogle Scholar
  213. 213.
    Li S, Chen N, Gaddes ER, Zhang X, Dong C, Wang Y (2015) A drosera-bioinspired hydrogel for catching and killing cancer cells. Sci Rep 5:14297. CrossRefGoogle Scholar
  214. 214.
    Lai J, Li S, Shi X et al (2017) Displacement and hybridization reactions in aptamer-functionalized hydrogels for biomimetic protein release and signal transduction. Chem Sci 8:7306–7311. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Fernanda Machado Croisfelt
    • 1
  • Louise Lacalendola Tundisi
    • 2
  • Janaína Artem Ataide
    • 2
    Email author
  • Edgar Silveira
    • 3
  • Elias Basile Tambourgi
    • 4
  • Angela Faustino Jozala
    • 5
  • Eliana Maria Barbosa Souto
    • 6
    • 7
  • Priscila Gava Mazzola
    • 2
  1. 1.Institute of BiologyUniversity of Campinas (UNICAMP)CampinasBrazil
  2. 2.Faculty of Pharmaceutical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil
  3. 3.Genetics and Biochemistry InstituteFederal University of Uberlândia (UFU)UberlândiaBrazil
  4. 4.School of Chemical EngineeringUniversity of Campinas (UNICAMP)CampinasBrazil
  5. 5.LAMINFE - Laboratory of Industrial Microbiology and Fermentation ProcessUniversity of Sorocaba (UNISO)SorocabaBrazil
  6. 6.Department of Pharmaceutical Technology, Faculty of PharmacyUniversity of Coimbra (FFUC)CoimbraPortugal
  7. 7.CEB - Centre of Biological EngineeringUniversity of MinhoBragaPortugal

Personalised recommendations