Skip to main content

Advertisement

SpringerLink
Log in

Long acting injectable formulations: the state of the arts and challenges of poly(lactic-co-glycolic acid) microsphere, hydrogel, organogel and liquid crystal

  • Review
  • Published:
Journal of Pharmaceutical Investigation Aims and scope Submit manuscript

Abstract

Background

Long-acting injectable formulations (LAIFs) have received substantial attention recently due to their advantages over conventional formulations, including easy administration, continuous and controlled release of drug over months, and the ability to maintain drug concentrations within the therapeutic range. The constant advances in biotechnology produce complex active pharmaceuticals that might be difficult to administer by conventional means. In particular, peptides, proteins, and antibodies are hard to administer orally given their physicochemical instability in the gastrointestinal tract and short half lives in blood. Therefore, LAIFs are a good candidate delivery system for such drugs. LAIFs reduce the frequency of application and improve patient compliance. For instance, LAIF-based antipsychotics can be more effective in patients with bipolar disorder and schizoaffective disorder.

Area covered

This review provides an overview of the various drug delivery technologies using LAIFs. Poly (lactic-co-glycolic acid) microspheres, hydrogels, organogels, and liquid crystals were chosen as representative LAIFs, and their preparation methods, advantages, limitations, challenges, and prospects are discussed.

Expert opinion

LAIFs are an attractive delivery system for bio-macromolecules that might participate in the new drug paradigm in the future. While each LAIF-based delivery technology has its own unique advantages, there are still some limitations that need to be overcome, and studies are being performed to understand and address these limitations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Adapted from Kazazi-Hyseni et al. (2014)

Fig. 2

Adapted from Ramazani et al. (2016)

Fig. 3

Adapted from Zamani et al. (2014)

Fig. 4

Adapted from Vintiloiu and Leroux (2008)

Fig. 5

Adapted from Qiu and Caffrey (2000)

Similar content being viewed by others

References

  • Al-Maaieh A, Flanagan DR (2001) Salt and cosolvent effects on ionic drug loading into microspheres using an O/W method. J Control Release 70:169–181

    Article  CAS  PubMed  Google Scholar 

  • Alonso-Sande M, des Rieux A, Fievez V, Sarmento B, Delgado A, Evora C, Remunan-Lopez C, Preat V, Alonso MJ (2013) Development of PLGA-mannosamine nanoparticles as oral protein carriers. Biomacromol 14:4046–4052

    Article  CAS  Google Scholar 

  • Andhariya JV, Choi S, Wang Y, Zhou Y, Burgess DJ, Shen J (2017) Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres. Int J Pharm 520:79–85

    Article  CAS  PubMed  Google Scholar 

  • Ashton RS, Banerjee A, Punyani S, Schaffer DV, Kane RS (2007) Scaffolds based on degradable alginate hydrogels and poly(lactide-co-glycolide) microspheres for stem cell culture. Biomaterials 28:5518–5525

    Article  CAS  PubMed  Google Scholar 

  • Barauskas J, Landh T (2003) Phase behavior of the phytantriol/water system. Langmuir 19(23):9562–9565

    Article  CAS  Google Scholar 

  • Bee SL, Hamid AZA, Mariatti M, Yahaya BH, Keemi Lim, Bee ST, Sin ST (2018) Approaches to improve therapeutic efficacy of biodegradable PLA/PLGA microspheres: a review. Polym Rev 58(3):495–536

    Article  CAS  Google Scholar 

  • Berger J, Reist M, Mayer JM, Felt O, Gurny R (2004) Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. Eur J Pharm Biopharm 57:35–52

    Article  CAS  PubMed  Google Scholar 

  • Bhattarai N, Gunn J, Zhang M (2010) Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev 62(1):83–99

    Article  CAS  PubMed  Google Scholar 

  • Binder WH, Sachsenhofer R (2007) ’Click’ chemistry in polymer and materials science. Macromol Rapid Commun 28:15–54

    Article  CAS  Google Scholar 

  • Chaw CS, Yang YY, Lim IJ, Phan TT (2003) Water-soluble betamethasone-loaded poly(lactide-co-glycolide) hollow microparticles as a sustained release dosage form. J Microencapsul 20:349–359

    Article  CAS  PubMed  Google Scholar 

  • Chou AI, Akintoye SO, Nicoll SB (2009) Photo-crosslinked alginate hydro-gels support enhanced matrix accumulation by nucleus pulposuscells in vivo. Osteoarthr Cartil 17:1377–1384

    Article  CAS  Google Scholar 

  • Chue P (2010) Risperidone long-acting injection. In: Haddad P, Lambert T, Lauriello J (eds) Antipsychotic long-acting injections. Oxford University Press, Oxford, pp 93–130

    Chapter  Google Scholar 

  • Chue P, Chue J (2012) A review of Olanzapine pamoate. Expert Opin Pharmacother 13:1661–1670

    Article  CAS  PubMed  Google Scholar 

  • Chun C, Lee SM, Kim SY, Yang HK, Song SC (2009) Thermosensitive poly (organophosphazene)-paclitaxel conjugate gels for antitumor applications. Biomaterials 30:2349–2360

    Article  CAS  PubMed  Google Scholar 

  • Clogston J, Caffrey M (2005) Controlling release from the lipidic cubic phase. Amino acids, peptides, proteins and nucleic acids. J Control Release 107:97–111

    Article  CAS  PubMed  Google Scholar 

  • Cohen S, Lobel E, Trevgoda A, Peled Y (1997) A novel in situ-forming ophthalmic drug delivery system from alginates undergoing gelation in the eye. J Control Release 44:201–208

    Article  CAS  Google Scholar 

  • Correia DM, Sencadas V, Ribeiro C, Martins PM, Martins P, Gama FM, Botelho G, Lanceros-Mendez S (2016) Processing and size range separation of pristine and magnetic poly (l-lactic acid) based microspheres for biomedical applications. J Colloid Interface Sci 476:79–86

    Article  CAS  PubMed  Google Scholar 

  • Correll CU, Citrome L, Haddad PM, Lauriello J, Olfson M, Calloway SM, Kane JM (2016) The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry 77:1–24

    Article  PubMed  Google Scholar 

  • da Silva AA Jr, de Matos JR, Formariz TP, Rossanezi G, Scarpa MV, do Egito ES, de Oliveira AG (2009) Thermal behavior and stability of biodegradable spray-dried microparticles containing triamcinolone. Int J Pharm 368:45–55

    Article  PubMed  CAS  Google Scholar 

  • Dasgupta D, Srinivasan S, Rochas C, Ajayaghosh A, Guenet JM (2009) Hybrid thermoreversible gels from covalent polymers and organogels. Langmuir 25(15):8593–8598

    Article  CAS  PubMed  Google Scholar 

  • D’Aurizio E, van Nostrum CF, van Steenbergen MJ, Sozio P, Siepmann F, Siepmann J, Hennink WE, Di Stefano A (2011) Preparation and characterization of poly(lactic-coglycolic acid) microspheres loaded with a labile antiparkinson prodrug. Int J Pharm 409:289–296

    Article  PubMed  CAS  Google Scholar 

  • Dean RL (2005) The preclinical development of Medisorb® Naltrexone, a once a month long-acting injection, for the treatment of alcohol dependence. Front Biosci 10:643–655

    Article  CAS  PubMed  Google Scholar 

  • Elisseeff J, Anseth K, Sims D, McIntosh W, Randolph M, Langer R (1999) Transdermal photopolymerization for minimally invasive implantation. Proc Natl Acad Sci USA 96:3104–3107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engstrom S (1990) Drug delivery from cubic and other lipid–water phases. Lipid Technol 2:42–45

    Google Scholar 

  • Ericsson B, Eriksson PO, Lofroth JE, Engstrom S (1991) Cubic phases as delivery systems for peptide drugs. ACS Sym Ser 469:251–265

    Article  CAS  Google Scholar 

  • Esposito CL, Kirilov P, Roullin VG (2018) Organogels, promising drug delivery systems: an update of state-of-the-art and recent applications. J Control Release 271:1–20

    Article  CAS  PubMed  Google Scholar 

  • Fakhari A, Phan Q, Berkland C (2014) Hyaluronic acid colloidal gels as self-assembling elastic biomaterials. J Biomed Mater Res B Appl Biomater 102:612–618

    Article  PubMed  CAS  Google Scholar 

  • Fong C, Wells D, Krodkiewska I, Booth J, Hartley PG (2007) Synthesis and mesophases of glycerate surfactants. J Phys Chem B 111(6):1384–1392

    Article  CAS  PubMed  Google Scholar 

  • Fong WK, Hanley T, Boyd BJ (2009) Stimuli responsive liquid crystals provide ‘on-demand’ drug delivery in vitro and in vivo. J Control Release 135:218–226

    Article  CAS  PubMed  Google Scholar 

  • Fredenberg S, Wahlgren M, Reslow M, Axelsson A (2011) The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems: a review. Int J Pharm 415:34–52

    Article  CAS  PubMed  Google Scholar 

  • Freiberg S, Zhu X (2004) Polymer microspheres for controlled drug release. Int J Pharm 282:1–18

    Article  CAS  PubMed  Google Scholar 

  • Gaignaux A, Reeff J, Siepmann F, Siepmann J, De Vriese C, Goole J, Amighi K (2012) Development and evaluation of sustained-release clonidine-loaded PLGA microparticles. Int J Pharm 437:20–28

    Article  CAS  PubMed  Google Scholar 

  • Galeska I, Kim TK, Patil SD, Bhardwaj U, Chatttopadhyay D, Papadimitrakopoulos F, Burgess DJ (2005) Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels. AAPS J7(1):E231–E240

    Article  Google Scholar 

  • Garg G, Saraf S, Saraf S (2007) Cubosomes: an overview. Biol Pharm Bull 30(2):350–353

    Article  CAS  PubMed  Google Scholar 

  • Garg T, Bilandi A, Kapoor B, Kumar S, Joshi R (2011) Organogels: advanced and novel drug delivery system. Int Res J Pharm 2(12):15–21

    CAS  Google Scholar 

  • Garner CM, Terech P, Allegraud JJ, Mistrot B, Nguyen P, Geyer A, Rivera D (1998) Thermoreversible gelation of organic liquids by arylcyclohexanol derivatives synthesis and characterisation of the gels. J Chem Soc Faraday Trans 94(15):2173–2179

    Article  CAS  Google Scholar 

  • Gigante AD, Lafer B, Yatham LN (2012) Long-acting injectable antipsychotics for the maintenance treatment of bipolar disorder. CNS Drugs 26:403–420

    Article  CAS  PubMed  Google Scholar 

  • Gilday E, Nasrallah HA (2012) Clinical pharmacology of paliperidone palmitate a parenteral long-acting formulation for the treatment of schizophrenia. Rev Recent Trials 7:2–9

    Article  CAS  Google Scholar 

  • Graffino M, Montemagni C, Mingrone C, Rocca P (2014) Long acting injectable antipsychotics in the treatment of schizophrenia: a review of literature. Riv Psichiatr 49:115–123

    PubMed  Google Scholar 

  • Grande I, Berk M, Birmaher B, Vieta E (2016) Bipolar disorder. Lancet 387:1561–1572

    Article  PubMed  Google Scholar 

  • Guo C, Wang J, Cao F, Lee RJ, Zhai G (2010) Lyotropic liquid crystal systems in drug delivery. Drug Discov Today 15(23–24):1032–1040

    Article  CAS  PubMed  Google Scholar 

  • Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 60:1638–1649

    Article  CAS  PubMed  Google Scholar 

  • Han K, Pan X, Chen M, Wang R, Xu Y, Feng M, Li G, Huang M, Wu C (2010) Phytantriol-based inverted type bicontinuous cubic phase for vascular embolization and drug sustained release. Eur J Pharm Sci 41(5):692–699

    Article  PubMed  CAS  Google Scholar 

  • Han FY, Thurecht KJ, Whittaker AK, Smith MT (2016) Bioerodable PLGA-based microparticles for producing sustained-release drug formulations and strategies for improving drug loading. Front Pharmacol 7:185

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hato M, Minamikawa H (1996) The effects of oligosaccharide stereochemistry on the physical properties of aqueous synthetic glycolipids. Langmuir 12(6):1658–1665

    Article  CAS  Google Scholar 

  • Hennink WE, van Nostrum CF (2002) Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev 54:13–36

    Article  CAS  PubMed  Google Scholar 

  • Hines DJ, Kaplan DL (2013) Poly (lactic-co-glycolic) acid controlled-release systems: experimental and modeling insights. Crit Rev Ther Drug Carrier Syst 30:257–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirlekar R, Jain S, Patel M, Garse H, Kadam V (2010) Hexosomes: a novel drug delivery system. Curr Drug Deliv 7(1):28–35

    Article  CAS  PubMed  Google Scholar 

  • Holland TA, Tessmar JK, Tabata Y, Mikos AG (2004) Transforming growth factor-beta 1 release from oligo(poly(ethylene glycol) fumarate) hydrogels in conditions that model the cartilage wound healing environment. J Control Release 94:101–114

    Article  CAS  PubMed  Google Scholar 

  • Huang X, Brazel CS (2003) Analysis of burst release of proxyphylline from poly(vinyl alcohol) hydrogels. Chem Eng Commun 190:519–532

    Article  CAS  Google Scholar 

  • Jann MW, Penzak SR (2018) Long-acting injectable second-generation antipsychotics: an update and comparison between agents. CNS Drugs 32:241–257

    Article  CAS  PubMed  Google Scholar 

  • Jaraswekin S, Prakongpan S, Bodmeier R (2007) Effect of poly(lactide-co-glycolide) molecular weight on the release of dexamethasone sodium phosphate from microparticles. J Microencapsul 24:117–128

    Article  CAS  PubMed  Google Scholar 

  • Jeong B, Bae YH, Kim SW (2000) Drug release from biodegradable injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers. J Control Release 63:155–163

    Article  CAS  PubMed  Google Scholar 

  • Jeong B, Kim SW, Bae YH (2002) Thermosensitive sol-gel reversible hydrogels. Adv Drug Deliv Rev 54(1):37–51

    Article  CAS  PubMed  Google Scholar 

  • Jia X, Yeo Y, Clifton RJ, Jiao T, Kohane DS, Kobler JB, Zeitels SM, Langer R (2006) Hyaluronic acid-based microgels and microgel networksfor vocal fold regeneration. Biomacromol 7:3336–3344

    Article  CAS  Google Scholar 

  • Jin R, Hiemstra C, Zhong Z, Feijen J (2007) Enzyme-mediated fast in situ formation of hydrogels from dextran-tyramine conjugates. Biomaterials 28:2791–2800

    Article  CAS  PubMed  Google Scholar 

  • Jin R, Moreira Teixeira LS, Dijkstra PJ, Karperien M, van Blitter-swijk CA, Zhong ZY, Feijen J (2009) Injectable chitosan-based hydrogelsfor cartilage tissue engineering. Biomaterials 30:2544–2551

    Article  CAS  PubMed  Google Scholar 

  • Jin R, Moreira Teixeira LS, Dijkstra PJ, van Blitterswijk CA, KarperienM Feijen J (2011) Chondrogenesis in injectable enzymatically crosslinked heparin/dextran hydrogels. J Control Release 152:186–195

    Article  CAS  PubMed  Google Scholar 

  • Johnson JA, Lewis DR, Diaz DD, Finn MG, Koberstein JT, Turro NJ (2006) Synthesis of degradable model networks via ATRP and click chemistry. J Am Chem Soc 128:6564–6565

    Article  CAS  PubMed  Google Scholar 

  • Kantaria S, Rees GD, Lawrence MJ (1999) Gelatin-stabilised microemulsion-based organogels: rheology and application in iontophoretic transdermal drug delivery. J Control Release 60(2–3):355–365

    Article  CAS  PubMed  Google Scholar 

  • Kazazi-Hyseni F, Landin M, Lathuile A, Veldhuis GJ, Rahimian S, Hennink WE, Kok RJ, van Nostrum CF (2014) Computer modeling assisted design of monodisperse PLGA microspheres with controlled porosity affords zero order release of an encapsulated macromolecule for 3 months. Pharm Res 31:2844–2856

    Article  CAS  PubMed  Google Scholar 

  • Kempe S, Mäder K (2012) In situ forming implants—an attractive formulation principle for parenteral depot formulations. J Control Release 161:668–679

    Article  CAS  PubMed  Google Scholar 

  • Khan F, Tare RS, Oreffo RO, Bradley M (2009) Versatile biocompatible polymer hydrogels: scaffolds for cell growth. Angew Chem Int Ed Engl 48:978–982

    Article  CAS  PubMed  Google Scholar 

  • Ki MH, Lim JL, Ko JY, Park SH, Kim JE, Cho HJ, Park ES, Kim DD (2014) A new injectable liquid crystal system for 1 month delivery of leuprolide. J Control Release 185:62–70

    Article  CAS  PubMed  Google Scholar 

  • Kim KS, Park SJ, Yang JA, Jeon JH, Bhang SH, Kim BS, Hahn SK (2011) Injectable hyaluronic acid-tyramine hydrogels for the treatment of rheumatoid arthritis. Acta Biomater 7:666–674

    Article  CAS  PubMed  Google Scholar 

  • Kim DH, Jahn A, Cho SJ, Kim JS, Ki MH, Kim DD (2015) Lyotropic liquid crystal systems in drug delivery: a review. J Pharm Investig 45(1):1–11

    Article  CAS  Google Scholar 

  • Klouda L, Mikos AG (2008) Thermoresponsive hydrogels in biomedical applications. Eur J Pharm Biopharm 68:34–45

    Article  CAS  PubMed  Google Scholar 

  • Koynova R, Tenchov B, Rapp G (1997) Low amounts of PEG-lipid induce cubic phase in phosphatidylethanolamine dispersions. Biochim Biophys Acta 1326(2):167–170

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni CV (2011) Nanostructural studies on monoelaidin-water systems at low temperatures. Langmuir 27(19):11790–11800

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni CV, Wachter W, Iglesias-Salto G, Engelskirchen S, Ahualli S (2011) Monoolein: a magic lipid? Phys Chem Chem Phys 13(8):3004–3021

    Article  CAS  PubMed  Google Scholar 

  • Kumar R, Katare OP (2005) Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review. AAPS Pharm Sci Tech 6(2):E298–E310

    Article  Google Scholar 

  • Kumar S, Haglund BO, Himmelstein KJ (1994) In situ-forming gels for ophthalmic drug delivery. J Ocul Pharmacol 10:47–56

    Article  CAS  PubMed  Google Scholar 

  • Ladet S, David L, Domard A (2008) Multi-membrane hydrogels. Nature 452:76–79

    Article  CAS  PubMed  Google Scholar 

  • Law MR, Soumerai SB, Ross-Degnan D, Adams AS (2008) A longitudinal study of medication nonadherence and hospitalization risk in schizophrenia. J Clin Psychiatry 69:47–53

    Article  PubMed  Google Scholar 

  • Leach JB, Schmidt CE (2005) Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds. Biomaterials 26:125–135

    Article  CAS  PubMed  Google Scholar 

  • Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–1879

    Article  CAS  PubMed  Google Scholar 

  • Lee LY, Ranganath SH, Fu Y, Zheng JL, Lee HS, Wang CH, Smith KA (2009) Paclitaxel release from micro-porous PLGA disks. Chem Eng Sci 64:4341–4349

    Article  CAS  Google Scholar 

  • Lee BK, Yun Y, Park K (2016) PLA micro-and nano-particles. Adv Drug Deliv Rev 107:176–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leslie SB, Puvvada S, Ratna BR, Rudolph AS (1996) Encapsulation of hemoglobin in a bicontinuous cubic phase lipid. Biochim Biophys Acta 1285(2):246–254

    Article  CAS  Google Scholar 

  • Lim PFC, Liu XY, Kang L, Ho PCL, Chan SY (2008) Physicochemical effects of terpenes on organogel for transdermal drug delivery. Int J Pharm 358(1–2):102–107

    Article  CAS  PubMed  Google Scholar 

  • Lynch ML, Ofori-Boateng A, Hippe A, Kochvar K, Spicer PT (2003) Enhanced loading of water-soluble actives into bicontinuous cubic phase liquid crystals using cationic surfactants. J Colloid Interface Sci 260(2):404–413

    Article  CAS  PubMed  Google Scholar 

  • Ma WJ, Yuan XB, Kang CS, Su T, Yuan XY, Pu PY, Sheng J (2008) Evaluation of blood circulation of polysaccharide surface-decorated PLA nanoparticles. Carbohydr Polym 72:75–81

    Article  CAS  Google Scholar 

  • Maia J, Ferreira L, Carvalho R, Ramos MA, Gil MH (2005) Synthesis and characterization of new injectable and degradable dextran-based hydrogels. Polymer 46:9604–9614

    Article  CAS  Google Scholar 

  • Maji SK, Malik S, Drew MG, Nandi AK, Banerjee A (2003) A synthetic tripeptide as a novel organo-gelator: a structural investigation. Tetrahedron Lett 44(21):4103–4107

    Article  CAS  Google Scholar 

  • Makadia HK, Siegel SJ (2011) Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 3:1377–1397

    Article  CAS  PubMed  Google Scholar 

  • Makino K, Nakajima T, Shikamura M, Ito F, Ando S, Kochi C, Inagawa H, Soma G, Terada H (2004) Efficient intracellular delivery of rifampicin to alveolar macrophages using rifampicin-loaded PLGA microspheres: effects of molecular weight and composition of PLGA on release of rifampicin. Colloids Surf B Biointerfaces 36:35–42

    Article  CAS  PubMed  Google Scholar 

  • Malik S, Maji SK, Banerjee A, Nandi AK (2002) A synthetic tripeptide as organogelator: elucidation of gelation mechanism. J Chem Soc, Perkin Trans 2(6):1177–1186

    Article  CAS  Google Scholar 

  • Malkoch M, Vestberg R, Gupta N, Mespouille L, Dubois P, Mason AF, Hedrick JL, Liao Q, Frank CW, Kingsbury K, Hawker CJ (2006) Synthesis of well-defined hydrogel networks using click chemistry. Chem Commun 26:2774–2776

    Article  CAS  Google Scholar 

  • Mank R, Rafler G, Nerlich B (1991) Parenterale depotarzneiformen auf der Basis von biologisch abbaubaren Polymeren. Phamazie 46:9–17

    CAS  Google Scholar 

  • Mezzenga R, Schurtenberger P, Burbidge A, Michel M (2005) Understanding foods as soft materials. Nat Mater 4(10):729

    Article  CAS  PubMed  Google Scholar 

  • Milak S, Zimmer A (2015) Glycerol monooleate liquid crystalline phases used in drug delivery systems. Int J Pharm 478(2):569–587

    Article  CAS  PubMed  Google Scholar 

  • Moses JE, Moorhouse AD (2007) The growing applications of click chemistry. Chem Soc Rev 36:1249–1262

    Article  CAS  PubMed  Google Scholar 

  • Motulsky A, Lafleur M, Couffin-Hoarau AC, Hoarau D, Boury F, Benoit JP, Leroux JC (2005) Characterization and biocompatibility of organogels based on l-alanine for parenteral drug delivery implants. Biomaterials 26(31):6242–6253

    Article  CAS  PubMed  Google Scholar 

  • Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM (2008) Nano/micro technologies for delivering macromolecular therapeutics using poly(D, L-lactide-co-glycolide) and its derivatives. J Control Release 125:193–209

    Article  CAS  PubMed  Google Scholar 

  • Murdan S, Gregoriadis G, Florence AT (1999a) Sorbitan monostearate/polysorbate 20 organogels containing niosomes: a delivery vehicle for antigens? Eur J Pharm Sci 8(3):177–185

    Article  CAS  PubMed  Google Scholar 

  • Murdan S, Van den Bergh B, Gregoriadis G, Florence AT (1999b) Water-in-sorbitan monostearate organogels (water-in-oil gels). J Pharm Sci 88(6):615–619

    Article  CAS  PubMed  Google Scholar 

  • Murru A, Manchia M, Tusconi M, Carpiniello B, Carpiniello B, Pacchiarotti I, Colom F, Vieta E (2016) Diagnostic reliability in schizoaffective disorder. Bipolar Disord 18:78–80

    Article  PubMed  Google Scholar 

  • Nair LS, Laurencin CT (2007) Biodegradable polymers as biomaterials. Prog Polym Sci 32:762–798

    Article  CAS  Google Scholar 

  • Nguyen MK, Lee DS (2010) Injectable biodegradable hydrogels. Macromol Biosci 10:563–579

    Article  CAS  PubMed  Google Scholar 

  • Nimmo CM, Shoichet MS (2011) Regenerative biomaterials that “click”:simple, aqueous-based protocols for hydrogel synthesis, surface immobilization, and 3D patterning. Bioconjugate Chem 22:2199–2209

    Article  CAS  Google Scholar 

  • Nuttelman CR, Tripodi MC, Anseth KS (2006) Dexamethasone-functionalized gels induce osteogenic differentiation of encapsulated hMSCs. J Biomed Mater Res A 76(1):183–195

    Article  PubMed  CAS  Google Scholar 

  • Ossipov DA, Brannvall K, Forsberg-Nilsson K, Hilborn J (2007) Formationof the first injectable poly(vinyl alcohol) hydrogel by mixing offunctional PVA precursors. J Appl Polym Sci 106:60–70

    Article  CAS  Google Scholar 

  • Overstreet DJ, Dutta D, Stabenfeldt SE, Vernon BL (2012) Injectable hydrogels. J Polym Sci B Polym Phys 50:881–903

    Article  CAS  Google Scholar 

  • Pal K, Banthia AK, Majumdar DK (2009) Polymeric hydrogels: characterization and biomedical applications. Des Monomers Polym 12(3):197–220

    Article  CAS  Google Scholar 

  • Peppas NA, Sahlin JJ (1996) Hydrogels as mucoadhesive and bioadhesive materials: a review. Biomaterials 17:1553–1561

    Article  CAS  PubMed  Google Scholar 

  • Peppas NA, Bures P, Leobandung W, Ichikawa H (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50:27–46

    Article  CAS  PubMed  Google Scholar 

  • Pereira IHL, Ayres E, Patricio PS, Goes AM, Gomide VS, Junior EP, Orefice RL (2010) Photopolymerizable and injectable polyurethanes for biomedical applications: synthesis and biocompatibility. Acta Biomater 6:3056–3066

    Article  CAS  PubMed  Google Scholar 

  • Perez A, Hernandez R, Velasco D, Voicu D, Mijangos C (2015) Poly (lactic-co-glycolic acid) particles prepared by microfluidics and conventional methods. Modulated particle size and rheology. J Colloid Interface Sci 441:90–97

    Article  CAS  PubMed  Google Scholar 

  • Petersen H, Ahlheimer M (2007) Sustained release formulation comprising octreotide and two or more polylactide-co-glycolide polymers. International Publication WO 2007/071395

  • Plourde F, Motulsky A, Couffin-Hoarau AC, Hoarau D, Ong H, Leroux JC (2005) First report on the efficacy of l-alanine-based in situ-forming implants for the long-term parenteral delivery of drugs. J Control Release 108(2–3):433–441

    Article  CAS  PubMed  Google Scholar 

  • Qi F, Wu J, Hao D, Yang T, Ren Y, Ma G, Su Z (2014) Comparative studies on the influences of primary emulsion preparation on properties of uniform-sized exenatide-loaded PLGA microspheres. Pharm Res 31:1566–1574

    Article  CAS  PubMed  Google Scholar 

  • Qiu H, Caffrey M (2000) The phase diagram of the monoolein/water system: metastability and equilibrium aspects. Biomaterials 21(3):223–234

    Article  CAS  PubMed  Google Scholar 

  • Ramazani F, Chen W, van Nostrum CF, Storm G, Kiessling F, Lammers T, Hennink WE, Kok RJ (2016) Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: state-of-the-art and challenges. Int J Pharm 499(1–2):358–367

    Article  CAS  PubMed  Google Scholar 

  • Rememar JF (2014) Making the leap from daily oral dosing to long acting injectables: lessons from the antipsychotics. Mol Pharm 11:1739–1749

    Article  CAS  Google Scholar 

  • Renard PE, Jordan O, Faes A, Petri-Fink A, Hofmann H, Ruefenacht D, Bosmand F, Buchegger F, Doelker E (2010) The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia. Biomaterials 31(4):691–705

    Article  PubMed  CAS  Google Scholar 

  • Rizwan SB, Boyd BJ, Rades T, Hook S (2010) Bicontinuous cubic liquid crystals as sustained delivery systems for peptides and proteins. Expert Opin Drug Deliv 7(10):1133–1144

    Article  CAS  PubMed  Google Scholar 

  • Rizwan SB, McBurney WT, Young K, Hanley T, Boyd BJ, Rades T, Hook S (2013) Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate robust cellular and humoral immune responses. J Control Release 165(1):16–21

    Article  CAS  PubMed  Google Scholar 

  • Rosca ID, Watari F, Uo M (2004) Microparticle formation and its mechanism in single and double emulsion solvent evaporation. J Control Release 99:271–280

    Article  CAS  PubMed  Google Scholar 

  • Ruel-Gariepy E, Leroux JC (2004) In situ-forming hydrogels: review of temperature sensitive systems. Eur J Pharm Biopharm 58:409–426

    Article  CAS  PubMed  Google Scholar 

  • Sadhale Y, Shah JC (1999) Biological activity of insulin in GMO gels and the effect of agitation. Int J Pharm 191(1):65–74

    Article  CAS  PubMed  Google Scholar 

  • Sagalowicz L, Mezzenga R, Leser ME (2006) Investigating reversed liquid crystalline mesophases. Curr Opin Colloid Interface Sci 11(4):224–229

    Article  CAS  Google Scholar 

  • Sahoo S, Kumar N, Bhattacharya C, Sagiri SS, Jain K, Pal K, Ray SS, Nayak B (2012) Organogels: Properties and applications in drug delivery. Des Monomers Polym 14(2):95–108

    Google Scholar 

  • Salamat-Miller N, Chittchang M, Johnston TP (2005) The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev 57:1666–1691

    Article  CAS  PubMed  Google Scholar 

  • Salzman PM, Raoufina A, Legacy S, Such P, Eramo A (2017) Plasma concentrations and dosing of 2 long-acting injectable formulations of aripiprazole. Neuropsychiatr Dis Treat 13:1125–1129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt C, Lautenschlaeger C, Collnot EM, Schumann M, Bojarski C, Schulzke JD, Lehr CM, Stallmach A (2013) Nano- and microscaled particles for drug targeting to inflamed intestinal mucosa: a first in vivo study in human patients. J Control Release 165:139–145

    Article  CAS  PubMed  Google Scholar 

  • Seddon JM, Templer RH (1993) Cubic phases of self-assembled amphiphilic aggregates. Philos Trans R Soc Lond 344(1672):377–401

    Article  CAS  Google Scholar 

  • Seddon JM, Templer RH (1995) Polymorphism of lipid-water systems. Handb Biol Phys 1:97–160

    Article  Google Scholar 

  • Shah JC, Sadhale Y, Chilukuri DM (2001) Cubic phase gels as drug delivery systems. Adv Drug Deliv Rev 47(2–3):229–250

    Article  CAS  PubMed  Google Scholar 

  • Shah RK, Shum HC, Rowat AC, Lee D, Agresti JJ, Utada AS, Chu L, Kim J, Fernandez-Nieves A, Martinez CJ, Weitz DA (2008) Designer emulsions using microfluidics. Mater Today 11:18–27

    Article  CAS  Google Scholar 

  • Shirley M, Perry CM (2014) Aripiprazole (Abilify Maintena): a review of its use as maintenance treatment for adult patients with schizophrenia. Drugs 74:1097–1110

    Article  CAS  PubMed  Google Scholar 

  • Sjölund M, Lindblom G, Rilfors L, Arvidson G (1987) Hydrophobic molecules in lecithin-water systems. I. Formation of reversed hexagonal phases at high and low water contents. Biophys J 52(2):145–153

    Article  PubMed  PubMed Central  Google Scholar 

  • Srividya B, Cardoza RM, Amin PD (2001) Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. J Control Release 73:205–211

    Article  CAS  PubMed  Google Scholar 

  • Stevens MM, Qanadilo HF, Langer R, Shastri VP (2004) A rapid-curing alginate gel system: utility in periosteum-derived cartilage tissue engineering. Biomaterials 25:887–894

    Article  CAS  PubMed  Google Scholar 

  • Stile RA, Healy KE (2001) Thermo-responsive peptide-modified hydrogels for tissue regeneration. Biomacromol 2:185–194

    Article  CAS  Google Scholar 

  • Suzuki M, Hanabusa K (2010) Polymer organogelators that make supramolecular organogels through physical cross-linking and self-assembly. Chem Soc Rev 39(2):455–463

    Article  CAS  PubMed  Google Scholar 

  • Suzuki M, Nigawara T, Yumoto M, Kimura M, Shirai H, Hanabusa K (2003) l-Lysine based gemini organogelators: their organogelation properties and thermally stable organogels. Org Biomol Chem 1(22):4124–4131

    Article  CAS  PubMed  Google Scholar 

  • Suzuki M, Setoguchi C, Shirai H, Hanabusa K (2007) Organogelation by polymer organogelators with al-lysine derivative: formation of a three-dimensional network consisting of supramolecular and conventional polymers. Chemistry 13(29):8193–8200

    Article  CAS  PubMed  Google Scholar 

  • Szlęk J, Pacławski A, Lau R, Jachowicz R, Kazemi P, Mendyk A (2016) Empirical search for factors affecting mean particle size of PLGA microspheres containing macromolecular drugs. Comput Methods Prog Biomed 134:137–147

    Article  Google Scholar 

  • Tan H, Chu CR, Payne KA, Marra KG (2009) Injectable in situ formingbiodegradable chitosan-hyaluronic acid based hydrogels for cartilage tissue engineering. Biomaterials 30:2499–2506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan ML, Choong PF, Dass CR (2010) Recent developments in liposomes, microparticles and nanoparticles for protein and peptide drug delivery. Peptides 31:184–193

    Article  CAS  PubMed  Google Scholar 

  • Tenchov B, Koynova R, Rapp G (1998) Accelerated formation of cubic phases in phosphatidylethanolamine dispersions. Biophys J 75(2):853–866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tessmar JK, Gopferich AM (2007) Matrices and scaffolds for protein delivery in tissue engineering. Adv Drug Deliv Rev 59:274–291

    Article  CAS  PubMed  Google Scholar 

  • Thambi T, Li Y, Lee DS (2017) Injectable hydrogels for sustained release of therapeutic agents. J Control Release 267:57–66

    Article  CAS  PubMed  Google Scholar 

  • Toro-Vazquez JF, Morales-Rueda JA, Dibildox-Alvarado E, Charó-Alonso M, Alonzo-Macias M, González-Chávez MM (2007) Thermal and textural properties of organogels developed by candelilla wax in safflower oil. J Am Oil Chem Soc 84(11):989–1000

    Article  CAS  Google Scholar 

  • Tran VT, Benoit JP, Venier-Julienne MC (2011) Why and how to prepare biodegradable, monodispersed, polymeric microparticles in the field of pharmacy? Int J Pharm 407:1–11

    Article  CAS  PubMed  Google Scholar 

  • Ungaro F, Biondi M, d’Angelo I, Indolfi L, Quaglia F, Netti PA, La Rotonda MI (2006) Microsphere-integrated collagen scaffolds for tissue engineering: effect of microsphere formulation and scaffold properties on protein release kinetics. J Control Release 113:128–136

    Article  CAS  PubMed  Google Scholar 

  • van Dijk M, van Nostrum CF, Hennink WE, Rijkers DT, Liskamp RM (2010) Synthesis and characterization of enzymatically biodegradable PEG and peptide-based hydrogels prepared by click chemistry. Biomacromol 11:1608–1614

    Article  CAS  Google Scholar 

  • Van Hove AH, Benoit DS (2015) Depot-based delivery systems for pro-angiogenic peptides: a review. Front Bioeng Biotechnol 3:102

    PubMed  PubMed Central  Google Scholar 

  • Varde NK, Pack DW (2004) Microspheres for controlled release drug delivery. Expert Opin Biol Ther 4:35–51

    Article  CAS  PubMed  Google Scholar 

  • Versypt ANF, Pack DW, Braatz RD (2013) Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres—a review. J Control Release 165:29–37

    Article  CAS  Google Scholar 

  • Vintiloiu A, Leroux JC (2008) Organogels and their use in drug delivery—a review. J Control Release 125(3):179–192

    Article  CAS  PubMed  Google Scholar 

  • Vintiloiu A, Lafleur M, Bastiat G, Leroux JC (2008) In situ-forming oleogel implant for rivastigmine delivery. Pharm Res 25(4):845–852

    Article  CAS  PubMed  Google Scholar 

  • Vladisavljević GT, Schubert H (2003) Influence of process parameters on droplet size distribution in SPG membrane emulsification and stability of prepared emulsion droplets. J Membr Sci 225:15–23

    Article  CAS  Google Scholar 

  • Wan F, Yang M (2016) Design of PLGA-based depot delivery systems for biopharmaceuticals prepared by spray drying. Int J Pharm 498:82–95

    Article  CAS  PubMed  Google Scholar 

  • Wang DA, Varghese S, Sharma B, Strehin I, Fermanian S, Gorham J, Fairbrother DH, Cascio B, Elisseeff JH (2007) Multifunctional chondroitinsulphate for cartilage tissue-biomaterial integration. Nat Mater 6:385–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D, Zhao J, Liu X, Sun F, Zhou Y, Teng L, Li Y (2014) Parenteral thermo-sensitive organogel for schizophrenia therapy, in vitro and in vivo evaluation. Eur J Pharm Sci 60:40–48

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Li Y, Wang X, Wang J, Tian H, Zhao P, Tian Y, Gu Y, Wang L, Wang C (2017) Droplet microfluidics for the production of microparticles and nanoparticles. Micromachines 8:22

    Article  PubMed Central  Google Scholar 

  • Weiden PJ, Kozma C, Grogg A, Locklear J (2004) Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv 55:886–891

    Article  PubMed  Google Scholar 

  • Wischke C, Schwendeman SP (2008) Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm 364:298–327

    Article  CAS  PubMed  Google Scholar 

  • Wright AJ, Marangoni AG (2006) Formation, structure, and rheological properties of ricinelaidic acid-vegetable oil organogels. J Am Oil Chem Soc 83(6):497–503

    Article  CAS  Google Scholar 

  • Xie H, She ZG, Wang S, Sharma G, Smith JW (2012) One-step fabrication of polymeric Janus nanoparticles for drug delivery. Langmuir 28(9):4459–4463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu XD, Zhang XZ, Cheng SX, Zhuo RX, Kennedy JF (2007) A strategy to introduce the pH sensitivity to temperature sensitive PNIPAAm hydrogels without weakening the thermosensitivity. Carbohydr Polym 68:416–423

    Article  CAS  Google Scholar 

  • Xu Q, Hashimoto M, Dang TT, Hoare T, Kohane DS, Whitesides GM, Langer R, Anderson DG (2009) Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow-focusing device for controlled drug delivery. Small 5(13):1575–1581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang JA, Yeom J, Hwang BW, Hoffman AS, Hahn SK (2014) In situ-forming injectable hydrogels for regenerative medicine. Prog Polym Sci 39:1973–1986

    Article  CAS  Google Scholar 

  • Ye M, Kim S, Park K (2010) Issues in long-term protein delivery using biodegradable microparticles. J Control Release 146:241–260

    Article  CAS  PubMed  Google Scholar 

  • Yu L, Ding J (2008) Injectable hydrogels as unique biomedical materials. Chem Soc Rev 37:1473–1481

    Article  CAS  PubMed  Google Scholar 

  • Yuan S, Lei F, Liu Z, Tong Q, Si T, Xu RX (2015) Coaxial electrospray of curcumin-loaded microparticles for sustained drug release. PLoS ONE 10(7):e0132609

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zamani M, Prabhakaran MP, Thian ES, Ramakrishna S (2014) Protein encapsulated core-shell structured particles prepared by coaxial electrospraying: investigation on material and processing variables. Int J Pharm 473(1–2):134–143

    Article  CAS  PubMed  Google Scholar 

  • Zandstra J, Hiemstra C, Petersen AH, Zuidema J, van Beuge MM, Rodriguez S, Lathuile AA, Veldhuis GJ, Steendam R, Bank RA, Popa ER (2014) Microsphere size influences the foreign body reaction. Eur Cell Mater 28:335–347

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Song Y, Page SW, Garg S (2018) Evaluation of transdermal drug permeation as modulated by lipoderm and pluronic lecithin organogel. J Pharm Sci 107(2):587–594

    Article  CAS  PubMed  Google Scholar 

  • Zhao LA, Weir MD, Xu HHK (2010) An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering. Biomaterials 31:6502–6510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng Shu X, Liu Y, Palumbo FS, Luo Y, Prestwich GD (2004) In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials 25:1339–1348

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07045240).

Author information

Authors and Affiliations

  1. College of Pharmacy, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju, 61452, Republic of Korea

    Won Young Lee, Md. Asadujjaman & Jun-Pil Jee

Authors
  1. Won Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Md. Asadujjaman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun-Pil Jee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun-Pil Jee.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest in this work.

Statement of human and animal rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, W.Y., Asadujjaman, M. & Jee, JP. Long acting injectable formulations: the state of the arts and challenges of poly(lactic-co-glycolic acid) microsphere, hydrogel, organogel and liquid crystal. J. Pharm. Investig. 49, 459–476 (2019). https://doi.org/10.1007/s40005-019-00449-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-019-00449-9

Keywords

Search

Navigation