Nanoprecipitation Process: From Particle Preparation to In Vivo Applications

  • Karim Miladi
  • Sana Sfar
  • Hatem FessiEmail author
  • Abdelhamid ElaissariEmail author


Nanoparticles have been widely prepared during the past decades. In fact, encapsulation could provide several advantages over conventional pharmaceutical forms (Miladi et al. in Int J Pharm 445(1–2):181–195, 2013; Campos et al. in J Colloid Sci Biotechnol 2(2):106–111, 2013; Grando et al. in J Colloid Sci Biotechnol 2(2):140–145, 2013; De Melo et al. in J Colloid Sci Biotechnol 2(2):146–152, 2013; Mazzaferro et al. in J Colloid Sci Biotechnol 1(2):210–217, 2012; Lira et al. in J Colloid Sci Biotechnol 2(2):123–129, 2013; Wang et al. in J Colloid Sci Biotechnol 1(2):192–200, 2012). Although, several techniques have been used for the preparation of submicron particles from preformed polymers, nanoprecipitation is regarded as a quite simple and reproducible technique that allows the obtaining of submicron-sized polymer particles. Additionally, many research works have focused on the enhancement of the reproducibility of the technique in order to render it more suitable for industrial applications. Nanoprecipitation is still widely used to prepare particulate carriers which are based on various polymers. Biomedical applications of such drug delivery systems are multiple (Rosset et al. in J Colloid Sci Biotechnol 1(2):218–224, 2012; Khan et al. in J Colloid Sci Biotechnol 1(1):122–128, 2012).


Supersaturation Nucleation Encapsulation Hydrophilic molecules PLGA particles Microfluidics Bilamination Anticancer agents Nanoprecipitation Flash nanoprecipitation Solvent displacement Interfacial deposition Nanocapsules Nanospheres 


  1. Ali H, Kalashnikova I, White MA, Sherman M, Rytting E (2013) Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model. Int J Pharm 454(1):149–157PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ali ME, Lamprecht A (2013) Polyethylene glycol as an alternative polymer solvent for nanoparticle preparation. Int J Pharm 456(1):135–142PubMedCrossRefGoogle Scholar
  3. Allémann E, Gurny R, Doelker E (1992) Preparation of aqueous polymeric nanodispersions by a reversible salting-out process: influence of process parameters on particle size. Int J Pharm 87(1–3):247–253CrossRefGoogle Scholar
  4. Almouazen E, Bourgeois S, Boussaïd A, Valot P, Malleval C, Fessi H et al (2012) Development of a nanoparticle-based system for the delivery of retinoic acid into macrophages. Int J Pharm 430(1–2):207–215PubMedCrossRefGoogle Scholar
  5. Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR et al (2010) Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochem Pharmacol 79(3):330–338PubMedCrossRefGoogle Scholar
  6. Arica B, Lamprecht A (2005) In vitro evaluation of betamethasone-loaded nanoparticles. Drug Dev Ind Pharm 31(1):19–24PubMedCrossRefGoogle Scholar
  7. Asadi H, Rostamizadeh K, Salari D, Hamidi M (2011) Preparation of biodegradable nanoparticles of tri-block PLA–PEG–PLA copolymer and determination of factors controlling the particle size using artificial neural network. J Microencapsul 28(5):406–416PubMedCrossRefGoogle Scholar
  8. Bally F, Garg DK, Serra CA, Hoarau Y, Anton N, Brochon C et al (2012) Improved size-tunable preparation of polymeric nanoparticles by microfluidic nanoprecipitation. Polymer 53(22):5045–5051CrossRefGoogle Scholar
  9. Barwal I, Sood A, Sharma M, Singh B, Yadav SC (2013) Development of stevioside Pluronic-F-68 copolymer based PLA-nanoparticles as an antidiabetic nanomedicine. Colloids Surf B Biointerfaces 101:510–516PubMedCrossRefGoogle Scholar
  10. Bazylińska U, Lewińska A, Lamch Ł, Wilk KA (2013) Polymeric nanocapsules and nanospheres for encapsulation and long sustained release of hydrophobic cyanine-type photosensitizer. Colloids Surf Physicochem Eng Asp [Internet]. mars 2013 [cité 1 mai 2013]; Disponible sur:
  11. Bernabeu E, Helguera G, Legaspi MJ, Gonzalez L, Hocht C, Taira C et al (2013) Paclitaxel-loaded PCL-TPGS nanoparticles: In vitro and in vivo performance compared with Abraxane(®). Colloids Surf B Biointerfaces 113C:43–50Google Scholar
  12. Bilati U, Allémann E, Doelker E (2005) Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci 24(1):67–75PubMedCrossRefGoogle Scholar
  13. Bilensoy E, Sarisozen C, Esendağli G, Doğan AL, Aktaş Y, Sen M et al (2009) Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of Mitomycin C to bladder tumors. Int J Pharm 371(1–2):170–176PubMedCrossRefGoogle Scholar
  14. Briancon S, Fessi H, Lecomte F, Lieto J (1999) Study of an original production process of nanoparticles by precipitation. Récents Prog. En Génie Procédés [Internet]. 1999 [cité 27 août 2014]. pp 157–164. Disponible sur:
  15. Le Broc-Ryckewaert D, Carpentier R, Lipka E, Daher S, Vaccher C, Betbeder D et al (2013) Development of innovative paclitaxel-loaded small PLGA nanoparticles: study of their antiproliferative activity and their molecular interactions on prostatic cancer cells. Int J Pharm 454(2):712–719PubMedCrossRefGoogle Scholar
  16. Budhian A, Siegel SJ, Winey KI (2007) Haloperidol-loaded PLGA nanoparticles: systematic study of particle size and drug content. Int J Pharm 336(2):367–375PubMedCrossRefGoogle Scholar
  17. Budijono SJ, Shan J, Yao N, Miura Y, Hoye T, Austin RH et al Synthesis of stable block-copolymer-protected NaYF4:Yb3+, Er3+ up-converting phosphor nanoparticles. Chem Mater 22(2):311–318Google Scholar
  18. Campos EVR, de Melo NFS, de Paula E, Rosa AH, Fraceto LF (2013) Screening of conditions for the preparation of poly(-caprolactone) nanocapsules containing the local anesthetic articaine. J Colloid Sci Biotechnol 2(2):106–111CrossRefGoogle Scholar
  19. Charcosset C, Fessi H (2005) Preparation of nanoparticles with a membrane contactor. J Membr Sci 266(1–2):115–120CrossRefGoogle Scholar
  20. Chen T, D’Addio SM, Kennedy MT, Swietlow A, Kevrekidis IG, Panagiotopoulos AZ et al (2009) Protected peptide nanoparticles: experiments and brownian dynamics simulations of the energetics of assembly. Nano Lett 9(6):2218–2222PubMedCrossRefGoogle Scholar
  21. Cheng F-Y, Wang SP-H, Su C-H, Tsai T-L, Wu P-C, Shieh D-B et al (2008) Stabilizer-free poly(lactide-co-glycolide) nanoparticles for multimodal biomedical probes. Biomaterials 29(13):2104–2112PubMedCrossRefGoogle Scholar
  22. Cheow WS, Hadinoto K (2010) Enhancing encapsulation efficiency of highly water-soluble antibiotic in poly(lactic-co-glycolic acid) nanoparticles: Modifications of standard nanoparticle preparation methods. Colloids Surf Physicochem Eng Asp 370(1–3):79–86CrossRefGoogle Scholar
  23. Chorny M, Fishbein I, Danenberg HD, Golomb G (2002) Lipophilic drug loaded nanospheres prepared by nanoprecipitation: effect of formulation variables on size, drug recovery and release kinetics. J Control Release 83(3):389–400PubMedCrossRefGoogle Scholar
  24. Chung JW, Neikirk C, Priestley RD (2013) Investigation of coumarin functionality on the formation of polymeric nanoparticles. J Colloid Interface Sci 396:16–22PubMedCrossRefGoogle Scholar
  25. Contado C, Vighi E, Dalpiaz A, Leo E (2013) Influence of secondary preparative parameters and aging effects on PLGA particle size distribution: a sedimentation field flow fractionation investigation. Anal Bioanal Chem 405(2–3):703–711PubMedCrossRefGoogle Scholar
  26. Costantino L, Gandolfi F, Tosi G, Rivasi F, Vandelli MA, Forni F (2005) Peptide-derivatized biodegradable nanoparticles able to cross the blood-brain barrier. J Control Release 108(1):84–96PubMedCrossRefGoogle Scholar
  27. Cırpanlı Y, Allard E, Passirani C, Bilensoy E, Lemaire L, Calış S et al (2011) Antitumoral activity of camptothecin-loaded nanoparticles in 9L rat glioma model. Int J Pharm 403(1–2):201–206PubMedCrossRefGoogle Scholar
  28. Danhier F, Lecouturier N, Vroman B, Jérôme C, Marchand-Brynaert J, Feron O et al (2009a) Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. J Control Release 133(1):11–17PubMedCrossRefGoogle Scholar
  29. Danhier F, Vroman B, Lecouturier N, Crokart N, Pourcelle V, Freichels H et al (2009b) Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with Paclitaxel. J Control Release 140(2):166–173PubMedCrossRefGoogle Scholar
  30. Das S, Das J, Samadder A, Paul A, Khuda-Bukhsh AR (2013a) Strategic formulation of apigenin-loaded PLGA nanoparticles for intracellular trafficking, DNA targeting and improved therapeutic effects in skin melanoma in vitro. Toxicol Lett 223(2):124–138PubMedCrossRefGoogle Scholar
  31. Das S, Das J, Samadder A, Paul A, Khuda-Bukhsh AR (2013b) Efficacy of PLGA-loaded apigenin nanoparticles in benzo[a]pyrene and ultraviolet-B induced skin cancer of mice: mitochondria mediated apoptotic signalling cascades. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 62:670–680CrossRefGoogle Scholar
  32. Das Neves J, Amiji M, Bahia MF, Sarmento B (2013) Assessing the physical-chemical properties and stability of dapivirine-loaded polymeric nanoparticles. Int J Pharm 456(2):307–314PubMedCrossRefGoogle Scholar
  33. Das S, Suresh PK (2011) Nanosuspension: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to amphotericin B. Nanomed Nanotechnol Biol Med 7(2):242–247CrossRefGoogle Scholar
  34. Das S, Suresh PK, Desmukh R (2010) Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomed Nanotechnol Biol Med 6(2):318–323CrossRefGoogle Scholar
  35. Davies JT (1975) Local eddy diffusivities related to «bursts» of fluid near solid walls. Chem Eng Sci 30(8):996–997CrossRefGoogle Scholar
  36. Dong Y, Feng S-S (2004) Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials 25(14):2843–2849PubMedCrossRefGoogle Scholar
  37. Dong Y, Feng S-S (2007) In vitro and in vivo evaluation of methoxy polyethylene glycol–polylactide (MPEG–PLA) nanoparticles for small-molecule drug chemotherapy. Biomaterials 28(28):4154–4160PubMedCrossRefGoogle Scholar
  38. D’Addio SM, Prud’homme RK (2011) Controlling drug nanoparticle formation by rapid precipitation. Adv Drug Deliv Rev 63(6):417–426PubMedCrossRefGoogle Scholar
  39. Eidi H, Joubert O, Attik G, Duval RE, Bottin MC, Hamouia A et al (2010) Cytotoxicity assessment of heparin nanoparticles in NR8383 macrophages. Int J Pharm 396(1–2):156–165PubMedCrossRefGoogle Scholar
  40. Eidi H, Joubert O, Némos C, Grandemange S, Mograbi B, Foliguet B et al (2012) Drug delivery by polymeric nanoparticles induces autophagy in macrophages. Int J Pharm 422(1–2):495–503PubMedCrossRefGoogle Scholar
  41. Esfandyari-Manesh M, Ghaedi Z, Asemi M, Khanavi M, Manayi A, Jamalifar H et al (2013) Study of antimicrobial activity of anethole and carvone loaded PLGA nanoparticles. J Pharm Res 7(4):290–295Google Scholar
  42. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55(1):R1–R4CrossRefGoogle Scholar
  43. Flory PJ (1969) Statistical mechanics of chain molecules. Interscience Publishers, New YorkGoogle Scholar
  44. Fonseca C, Simões S, Gaspar R (2002) Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Control Release 83(2):273–286PubMedCrossRefGoogle Scholar
  45. Gao H, Yang Y, Fan Y, Ma J (2006) Conjugates of poly(dl-lactic acid) with ethylenediamino or diethylenetriamino bridged bis(β-cyclodextrin)s and their nanoparticles as protein delivery systems. J Control Release 112(3):301–311PubMedCrossRefGoogle Scholar
  46. Govender T, Stolnik S, Garnett MC, Illum L, Davis SS (1999) PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J Control Release 57(2):171–185PubMedCrossRefGoogle Scholar
  47. Grando CRC, Guimarães CA, Mercuri LP, Matos JDR, Santana MHA (2013) Preparation and characterization of solid lipid nanoparticles loaded with racemic mitotane. J Colloid Sci Biotechnol 2(2):140–145CrossRefGoogle Scholar
  48. Guhagarkar SA, Gaikwad RV, Samad A, Malshe VC, Devarajan PV (2010) Polyethylene sebacate–doxorubicin nanoparticles for hepatic targeting. Int J Pharm 401(1–2):113–122PubMedCrossRefGoogle Scholar
  49. Guhagarkar SA, Malshe VC, Devarajan PV (2009) Nanoparticles of polyethylene sebacate: a new biodegradable polymer. AAPS PharmSciTech 10(3):935–942PubMedPubMedCentralCrossRefGoogle Scholar
  50. Gupta H, Aqil M, Khar RK, Ali A, Bhatnagar A, Mittal G (2010) Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery. Nanomed Nanotechnol Biol Med 6(2):324–333CrossRefGoogle Scholar
  51. Han S, Li M, Liu X, Gao H, Wu Y (2013) Construction of amphiphilic copolymer nanoparticles based on gelatin as drug carriers for doxorubicin delivery. Colloids Surf B Biointerfaces 102:833–841PubMedCrossRefGoogle Scholar
  52. Holgado MA, Martin-banderas, Alvarez-fuentes, Duran-lobato, Prados J, Melguizo et al (2012) Cannabinoid derivate-loaded PLGA nanocarriers for oral administration: formulation, characterization, and cytotoxicity studies. Int J Nanomed 5793Google Scholar
  53. Hyvönen S, Peltonen L, Karjalainen M, Hirvonen J (2005) Effect of nanoprecipitation on the physicochemical properties of low molecular weight poly(l-lactic acid) nanoparticles loaded with salbutamol sulphate and beclomethasone dipropionate. Int J Pharm 295(1–2):269–281PubMedCrossRefGoogle Scholar
  54. Johnson BK, Prud’homme RK (2003a) Flash nanoprecipitation of organic actives and block copolymers using a confined impinging jets mixer. Aust J Chem 56(10):1021–1024CrossRefGoogle Scholar
  55. Johnson BK, Prud’homme RK (2003b) Chemical processing and micromixing in confined impinging jets. AIChE J 49(9):2264–2282CrossRefGoogle Scholar
  56. Joshi SA, Chavhan SS, Sawant KK (2010) Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm 76(2):189–199PubMedCrossRefGoogle Scholar
  57. Kaewprapan K, Inprakhon P, Marie E, Durand A (2012) Enzymatically degradable nanoparticles of dextran esters as potential drug delivery systems. Carbohydr Polym 88(3):875–881CrossRefGoogle Scholar
  58. Karnik R, Gu F, Basto P, Cannizzaro C, Dean L, Kyei-Manu W et al (2008) Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett 8(9):2906–2912PubMedCrossRefGoogle Scholar
  59. Katara R, Majumdar DK (2013) Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery. Colloids Surf B Biointerfaces 103:455–462PubMedCrossRefGoogle Scholar
  60. Khan MS, Vishakante GD, Bathool A (2012) Development and characterization of brimonidine tartrate loaded eudragit nanosuspensions for ocular drug delivery. J Colloid Sci Biotechnol 1(1):122–128CrossRefGoogle Scholar
  61. Khayata N, Abdelwahed W, Chehna MF, Charcosset C, Fessi H (2012a) Preparation of vitamin E loaded nanocapsules by the nanoprecipitation method: from laboratory scale to large scale using a membrane contactor. Int J Pharm 423(2):419–427PubMedCrossRefGoogle Scholar
  62. Khayata N, Abdelwahed W, Chehna MF, Charcosset C, Fessi H (2012b) Stability study and lyophilization of vitamin E-loaded nanocapsules prepared by membrane contactor. Int J Pharm 439(1–2):254–259PubMedCrossRefGoogle Scholar
  63. Krishnakumar N, Sulfikkarali N, RajendraPrasad N, Karthikeyan S (2011) Enhanced anticancer activity of naringenin-loaded nanoparticles in human cervical (HeLa) cancer cells. Biomed Prev Nutr 1(4):223–231CrossRefGoogle Scholar
  64. Kumar V, Adamson DH (2010) Prud’homme RK. Fluorescent polymeric nanoparticles: aggregation and phase behavior of pyrene and amphotericin B molecules in nanoparticle cores. Small Weinh Bergstr Ger 6(24):2907–2914CrossRefGoogle Scholar
  65. Kumar A, Wonganan P, Sandoval MA, Li X, Zhu S, Cui Z (2012) Microneedle-mediated transcutaneous immunization with plasmid DNA coated on cationic PLGA nanoparticles. J Control Release 163(2):230–239PubMedPubMedCentralCrossRefGoogle Scholar
  66. Lamprecht A, Ubrich N, Yamamoto H, Schäfer U, Takeuchi H, Lehr CM et al (2001) Design of rolipram-loaded nanoparticles: comparison of two preparation methods. J Control Release 71(3):297–306PubMedCrossRefGoogle Scholar
  67. Lassalle V, Ferreira ML (2007) PLA nano- and microparticles for drug delivery: an overview of the methods of preparation. Macromol Biosci 7(6):767–783PubMedCrossRefGoogle Scholar
  68. Lee SJ, Hong G-Y, Jeong Y-I, Kang M-S, Oh J-S, Song C-E et al (2012) Paclitaxel-incorporated nanoparticles of hydrophobized polysaccharide and their antitumor activity. Int J Pharm 433(1–2):121–128PubMedCrossRefGoogle Scholar
  69. Legrand P, Lesieur S, Bochot A, Gref R, Raatjes W, Barratt G et al (2007) Influence of polymer behaviour in organic solution on the production of polylactide nanoparticles by nanoprecipitation. Int J Pharm 344(1–2):33–43PubMedCrossRefGoogle Scholar
  70. Leo E, Brina B, Forni F, Vandelli MA (2004) In vitro evaluation of PLA nanoparticles containing a lipophilic drug in water-soluble or insoluble form. Int J Pharm 278(1):133–141PubMedCrossRefGoogle Scholar
  71. Leroueil-Le Verger M, Fluckiger L, Kim Y-I, Hoffman M, Maincent P (1998) Preparation and characterization of nanoparticles containing an antihypertensive agent. Eur J Pharm Biopharm 46(2):137–143PubMedCrossRefGoogle Scholar
  72. Letchford K, Burt H (2007) A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. Eur J Pharm Biopharm 65(3):259–269PubMedCrossRefGoogle Scholar
  73. Letchford K, Liggins R, Wasan KM, Burt H (2009) In vitro human plasma distribution of nanoparticulate paclitaxel is dependent on the physicochemical properties of poly(ethylene glycol)-block-poly(caprolactone) nanoparticles. Eur J Pharm Biopharm 71(2):196–206PubMedCrossRefGoogle Scholar
  74. Limayem Blouza I, Charcosset C, Sfar S, Fessi H (2006) Preparation and characterization of spironolactone-loaded nanocapsules for paediatric use. Int J Pharm 325(1–2):124–131PubMedCrossRefGoogle Scholar
  75. Lince F, Marchisio DL, Barresi AA (2008) Strategies to control the particle size distribution of poly-ε-caprolactone nanoparticles for pharmaceutical applications. J Colloid Interface Sci 322(2):505–515PubMedCrossRefGoogle Scholar
  76. Lince F, Marchisio DL, Barresi AA (2011) A comparative study for nanoparticle production with passive mixers via solvent-displacement: use of CFD models for optimization and design. Chem Eng Process Process Intensif 50(4):356–368CrossRefGoogle Scholar
  77. Lira AAM, Cordo PLA, Nogueira ECF, Almeida EDP, Junior RALC, Nunes RS et al (2013) Optimization of topical all-trans retinoic acid penetration using poly-d,l-lactide and poly-d,l-lactide-co-glycolide microparticles. J Colloid Sci Biotechnol 2(2):123–129CrossRefGoogle Scholar
  78. Liu Y, Li K, Liu B, Feng S-S (2010) A strategy for precision engineering of nanoparticles of biodegradable copolymers for quantitative control of targeted drug delivery. Biomaterials 31(35):9145–9155PubMedCrossRefGoogle Scholar
  79. Liu Q, Li R, Zhu Z, Qian X, Guan W, Yu L et al (2012) Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles. Int J Pharm 430(1–2):350–358PubMedCrossRefGoogle Scholar
  80. Loyer P, Bedhouche W, Huang ZW, Cammas-Marion S (2013) Degradable and biocompatible nanoparticles decorated with cyclic RGD peptide for efficient drug delivery to hepatoma cells in vitro. Int J Pharm 454(2):727–737PubMedCrossRefGoogle Scholar
  81. Mazzaferro S, Bouchemal K, Maksimenko A, Skanji R, Opolon P, Ponchel G (2012) Reduced intestinal toxicity of docetaxel loaded into mucoadhesive nanoparticles, in mouse xenograft model. J Colloid Sci Biotechnol 1(2):210–217CrossRefGoogle Scholar
  82. Mazzarino L, Travelet C, Ortega-Murillo S, Otsuka I, Pignot-Paintrand I, Lemos-Senna E et al (2012) Elaboration of chitosan-coated nanoparticles loaded with curcumin for mucoadhesive applications. J Colloid Interface Sci 370(1):58–66PubMedCrossRefGoogle Scholar
  83. McManamey WJ, Davies JT, Woollen JM, Coe JR (1973) The influence of molecular diffusion on mass transfer between turbulent liquids. Chem Eng Sci 28(4):1061–1069CrossRefGoogle Scholar
  84. De Melo NFS, Campos EVR, de Paula E, Rosa AH, Fraceto LF (2013) Factorial design and characterization studies for articaine hydrochloride loaded alginate/chitosan nanoparticles. J Colloid Sci Biotechnol 2(2):146–152CrossRefGoogle Scholar
  85. Memisoglu-Bilensoy E, Vural I, Bochot A, Renoir JM, Duchene D, Hincal AA (2005) Tamoxifen citrate loaded amphiphilic beta-cyclodextrin nanoparticles: in vitro characterization and cytotoxicity. J Control Release 104(3):489–496PubMedCrossRefGoogle Scholar
  86. De Miguel L, Noiray M, Surpateanu G, Iorga BI, Ponchel G (2013) Poly(γ-benzyl-l-glutamate)-PEG-alendronate multivalent nanoparticles for bone targeting. Int J Pharm 460(1–2):73–82PubMedGoogle Scholar
  87. Miladi K, Sfar S, Fessi H, Elaissari A (2013) Drug carriers in osteoporosis: preparation, drug encapsulation and applications. Int J Pharm 445(1–2):181–195PubMedCrossRefGoogle Scholar
  88. Moinard-Chécot D, Chevalier Y, Briançon S, Beney L, Fessi H (2008) Mechanism of nanocapsules formation by the emulsion–diffusion process. J Colloid Interface Sci 317(2):458–468PubMedCrossRefGoogle Scholar
  89. Mondal N, Halder KK, Kamila MM, Debnath MC, Pal TK, Ghosal SK et al (2010) Preparation, characterization, and biodistribution of letrozole loaded PLGA nanoparticles in Ehrlich Ascites tumor bearing mice. Int J Pharm 397(1–2):194–200PubMedCrossRefGoogle Scholar
  90. Mora-Huertas CE, Fessi H, Elaissari A (2010) Polymer-based nanocapsules for drug delivery. Int J Pharm 385(1–2):113–142PubMedCrossRefGoogle Scholar
  91. Moraes CM, de Matos AP, de Paula E, Rosa AH, Fraceto LF (2009) Benzocaine loaded biodegradable poly-(d,l-lactide-co-glycolide) nanocapsules: factorial design and characterization. Mater Sci Eng B 165(3):243–246CrossRefGoogle Scholar
  92. Murakami H, Kawashima Y, Niwa T, Hino T, Takeuchi H, Kobayashi M (1997) Influence of the degrees of hydrolyzation and polymerization of poly(vinylalcohol) on the preparation and properties of poly(dl-lactide-co-glycolide) nanoparticle. Int J Pharm 149(1):43–49CrossRefGoogle Scholar
  93. Musumeci T, Bucolo C, Carbone C, Pignatello R, Drago F, Puglisi G (2013) Polymeric nanoparticles augment the ocular hypotensive effect of melatonin in rabbits. Int J Pharm 440(2):135–140PubMedCrossRefGoogle Scholar
  94. Muthu MS, Rawat MK, Mishra A, Singh S (2009) PLGA nanoparticle formulations of risperidone: preparation and neuropharmacological evaluation. Nanomed Nanotechnol Biol Med 5(3):323–333CrossRefGoogle Scholar
  95. Nafee N, Youssef A, El-Gowelli H, Asem H, Kandil S (2013) Antibiotic-free nanotherapeutics: Hypericin nanoparticles thereof for improved in vitro and in vivo antimicrobial photodynamic therapy and wound healing. Int J Pharm 454(1):249–258PubMedCrossRefGoogle Scholar
  96. Nagasawa H, Aoki N, Mae K (2005) Design of a new micromixer for instant mixing based on the collision of micro segments. Chem Eng Technol 28(3):324–330CrossRefGoogle Scholar
  97. Nehilla B, Bergkvist M, Popat K, Desai T (2008) Purified and surfactant-free coenzyme Q10-loaded biodegradable nanoparticles. Int J Pharm 348(1–2):107–114PubMedCrossRefGoogle Scholar
  98. Noronha CM, Granada AF, de Carvalho SM, Lino RC, de OB Maciel MV, Barreto PLM (2013) Optimization of α-tocopherol loaded nanocapsules by the nanoprecipitation method. Ind Crops Prod 50:896–903CrossRefGoogle Scholar
  99. Paul A, Das S, Das J, Samadder A, Khuda-Bukhsh AR (2013) Cytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo. Toxicol Lett 222(1):10–22PubMedCrossRefGoogle Scholar
  100. Pavot V, Rochereau N, Primard C, Genin C, Perouzel E, Lioux T et al (2013) Encapsulation of Nod1 and Nod2 receptor ligands into poly(lactic acid) nanoparticles potentiates their immune properties. J Control Release 167(1):60–67PubMedCrossRefGoogle Scholar
  101. Peltonen L, Aitta J, Hyvönen S, Karjalainen M, Hirvonen J (2004) Improved entrapment efficiency of hydrophilic drug substance during nanoprecipitation of poly(l)lactide nanoparticles. AAPS PharmSciTech 5(1):E16PubMedGoogle Scholar
  102. Peracchia MT, Fattal E, Desmaële D, Besnard M, Noël JP, Gomis JM et al (1999) Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting. J Control Release 60(1):121–128PubMedCrossRefGoogle Scholar
  103. Perret F, Duffour M, Chevalier Y, Parrot-Lopez H (2013a) Design, synthesis, and in vitro evaluation of new amphiphilic cyclodextrin-based nanoparticles for the incorporation and controlled release of acyclovir. Eur J Pharm Biopharm 83(1):25–32PubMedCrossRefGoogle Scholar
  104. Perret F, Marminon C, Zeinyeh W, Nebois P, Bollacke A, Jose J et al (2013b) Preparation and characterization of CK2 inhibitor-loaded cyclodextrin nanoparticles for drug delivery. Int J Pharm 441(1–2):491–498PubMedCrossRefGoogle Scholar
  105. Pertuit D, Moulari B, Betz T, Nadaradjane A, Neumann D, Ismaïli L et al (2007) 5-amino salicylic acid bound nanoparticles for the therapy of inflammatory bowel disease. J Control Release 123(3):211–218PubMedCrossRefGoogle Scholar
  106. Peter Christoper GV, Vijaya Raghavan C, Siddharth K, Siva Selva Kumar M, Hari Prasad R Formulation and optimization of coated PLGA—zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency. Saudi Pharm J [Internet]. [cité 23 déc 2013]; Disponible sur:
  107. Plasari E, Grisoni PH, Villermaux J (1997) Influence of process parameters on the precipitation of organic nanoparticles by drowning-out. Chem Eng Res Des 75(2):237–244CrossRefGoogle Scholar
  108. Quintanar-Guerrero D, Allémann E, Doelker E, Fessi H (1997) A mechanistic study of the formation of polymer nanoparticles by the emulsification-diffusion technique. Colloid Polym Sci 275(7):640–647CrossRefGoogle Scholar
  109. Quintanar-Guerrero D, Allémann E, Fessi H, Doelker E (1998) Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Dev Ind Pharm 24(12):1113–1128PubMedCrossRefGoogle Scholar
  110. Quintanar-Guerrero D, Fessi H, Allémann E, Doelker E (1996) Influence of stabilizing agents and preparative variables on the formation of poly(d,l-lactic acid) nanoparticles by an emulsification-diffusion technique. Int J Pharm 143(2):133–141CrossRefGoogle Scholar
  111. Raffin Pohlmann A, Weiss V, Mertins O, Pesce da Silveira N, Stanisçuaski Guterres S (2002) Spray-dried indomethacin-loaded polyester nanocapsules and nanospheres: development, stability evaluation and nanostructure models. Eur J Pharm Sci 16(4–5):305–312PubMedCrossRefGoogle Scholar
  112. Rhee M, Valencia PM, Rodriguez MI, Langer R, Farokhzad OC, Karnik R (2011) Synthesis of size-tunable polymeric nanoparticles enabled by 3D hydrodynamic flow focusing in single-layer microchannels. Adv Mater 23(12):79–83CrossRefGoogle Scholar
  113. Rosset V, Ahmed N, Zaanoun I, Stella B, Fessi H, Elaissari A (2012) Elaboration of argan oil nanocapsules containing naproxen for cosmetic and transdermal local application. J Colloid Sci Biotechnol 1(2):218–224CrossRefGoogle Scholar
  114. Sanson C, Schatz C, Le Meins J-F, Soum A, Thévenot J, Garanger E et al (2010) A simple method to achieve high doxorubicin loading in biodegradable polymersomes. J Control Release 147(3):428–435PubMedCrossRefGoogle Scholar
  115. Seju U, Kumar A, Sawant KK (2011) Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: In vitro and in vivo studies. Acta Biomater 7(12):4169–4176PubMedCrossRefGoogle Scholar
  116. Seremeta KP, Chiappetta DA, Sosnik A (2013) Poly(ε-caprolactone), Eudragit® RS 100 and poly(ε-caprolactone)/Eudragit® RS 100 blend submicron particles for the sustained release of the antiretroviral efavirenz. Colloids Surf B Biointerfaces 102:441–449PubMedCrossRefGoogle Scholar
  117. Shah U, Joshi G, Sawant K (2014) Improvement in antihypertensive and antianginal effects of felodipine by enhanced absorption from PLGA nanoparticles optimized by factorial design. Mater Sci Eng C 35:153–163CrossRefGoogle Scholar
  118. Shi L, Shan J, Ju Y, Aikens P, Prud’homme RK (2012) Nanoparticles as delivery vehicles for sunscreen agents. Colloids Surf Physicochem Eng Asp 396:122–129CrossRefGoogle Scholar
  119. Simşek S, Eroğlu H, Kurum B, Ulubayram K (2013) Brain targeting of Atorvastatin loaded amphiphilic PLGA-b-PEG nanoparticles. J Microencapsul 30(1):10–20PubMedCrossRefGoogle Scholar
  120. Siqueira-Moura MP, Primo FL, Espreafico EM, Tedesco AC (2013) Development, characterization, and photocytotoxicity assessment on human melanoma of chloroaluminum phthalocyanine nanocapsules. Mater Sci Eng C 33(3):1744–1752CrossRefGoogle Scholar
  121. Stainmesse S, Orecchioni A-M, Nakache E, Puisieux F, Fessi H (1995) Formation and stabilization of a biodegradable polymeric colloidal suspension of nanoparticles. Colloid Polym Sci 273(5):505–511CrossRefGoogle Scholar
  122. Suen W-LL, Chau Y (2013) Specific uptake of folate-decorated triamcinolone-encapsulating nanoparticles by retinal pigment epithelium cells enhances and prolongs antiangiogenic activity. J Control Release 67(1):21–28CrossRefGoogle Scholar
  123. Tao Y, Ning M, Dou H (2013) A novel therapeutic system for malignant glioma: nanoformulation, pharmacokinetic, and anticancer properties of cell-nano-drug delivery. Nanomed Nanotechnol Biol Med févr 9(2):222–232CrossRefGoogle Scholar
  124. Thioune O, Fessi H, Devissaguet JP, Puisieux F (1997) Preparation of pseudolatex by nanoprecipitation: Influence of the solvent nature on intrinsic viscosity and interaction constant. Int J Pharm 146(2):233–238CrossRefGoogle Scholar
  125. Tosi G, Costantino L, Rivasi F, Ruozi B, Leo E, Vergoni AV et al (2007) Targeting the central nervous system: in vivo experiments with peptide-derivatized nanoparticles loaded with loperamide and rhodamine-123. J Control Release 122(1):1–9PubMedCrossRefGoogle Scholar
  126. Tosi G, Vergoni AV, Ruozi B, Bondioli L, Badiali L, Rivasi F et al (2010) Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: in vivo pharmacological evidence and biodistribution. J Control Release 145(1):49–57PubMedCrossRefGoogle Scholar
  127. Ubrich N, Schmidt C, Bodmeier R, Hoffman M, Maincent P (2005) Oral evaluation in rabbits of cyclosporin-loaded Eudragit RS or RL nanoparticles. Int J Pharm 288(1):169–175PubMedCrossRefGoogle Scholar
  128. Valente I, Celasco E, Marchisio DL, Barresi AA (2012) Nanoprecipitation in confined impinging jets mixers: Production, characterization and scale-up of pegylated nanospheres and nanocapsules for pharmaceutical use. Chem Eng Sci 77:217–227CrossRefGoogle Scholar
  129. Van de Ven H, Paulussen C, Feijens PB, Matheeussen A, Rombaut P, Kayaert P et al (2012) PLGA nanoparticles and nanosuspensions with amphotericin B: potent in vitro and in vivo alternatives to Fungizone and Am Bisome. J Control Release 161(3):795–803PubMedCrossRefGoogle Scholar
  130. Vila A, Gill H, McCallion O, Alonso MJ (2004) Transport of PLA–PEG particles across the nasal mucosa: effect of particle size and PEG coating density. J Control Release 98(2):231–244PubMedCrossRefGoogle Scholar
  131. Wang J, Feng S-S, Wang S, Chen Z-Y (2010) Evaluation of cationic nanoparticles of biodegradable copolymers as siRNA delivery system for hepatitis B treatment. Int J Pharm 400(1–2):194–200PubMedCrossRefGoogle Scholar
  132. Wang F, Li J, Wang C (2012) Hydrophilic and fluorescent colloidal nanorods of MWNTs as effective targeted drug carrier. J Colloid Sci Biotechnol 1(2):192–200CrossRefGoogle Scholar
  133. Wang G, Yu B, Wu Y, Huang B, Yuan Y, Liu CS (2013) Controlled preparation and antitumor efficacy of vitamin E TPGS-functionalized PLGA nanoparticles for delivery of paclitaxel. Int J Pharm 446(1–2):24–33PubMedCrossRefGoogle Scholar
  134. Yedomon B, Fessi H, Charcosset C (2013) Preparation of bovine serum albumin (BSA) nanoparticles by desolvation using a membrane contactor: a new tool for large scale production. Eur J Pharm Biopharm 85(3):398–405PubMedCrossRefGoogle Scholar
  135. Yenice I, Mocan MC, Palaska E, Bochot A, Bilensoy E, Vural I et al (2008) Hyaluronic acid coated poly-epsilon-caprolactone nanospheres deliver high concentrations of cyclosporine A into the cornea. Exp Eye Res 87(3):162–167PubMedCrossRefGoogle Scholar
  136. Yuan X-B, Yuan Y-B, Jiang W, Liu J, Tian E-J, Shun H-M et al (2008) Preparation of rapamycin-loaded chitosan/PLA nanoparticles for immunosuppression in corneal transplantation. Int J Pharm 349(1–2):241–248PubMedCrossRefGoogle Scholar
  137. Zhang X, Wang Y, Zheng C, Li C (2012) Phenylboronic acid-functionalized glycopolymeric nanoparticles for biomacromolecules delivery across nasal respiratory. Eur J Pharm Biopharm 82(1):76–84PubMedCrossRefGoogle Scholar
  138. Zhang L, Yang M, Wang Q, Li Y, Guo R, Jiang X et al (2007) 10-Hydroxycamptothecin loaded nanoparticles: preparation and antitumor activity in mice. J Control Release 119(2):153–162PubMedCrossRefGoogle Scholar
  139. Zhang Y, Zhuo R (2005) Synthesis and in vitro drug release behavior of amphiphilic triblock copolymer nanoparticles based on poly(ethylene glycol) and polycaprolactone. Biomaterials 26(33):6736–6742PubMedCrossRefGoogle Scholar
  140. Zili Z, Sfar S, Fessi H (2005) Preparation and characterization of poly-epsilon-caprolactone nanoparticles containing griseofulvin. Int J Pharm 294(1–2):261–267PubMedCrossRefGoogle Scholar
  141. Zweers MLT, Grijpma DW, Engbers GHM, Feijen J (2003) The preparation of monodisperse biodegradable polyester nanoparticles with a controlled size. J Biomed Mater Res B Appl Biomater 66(2):559–566PubMedCrossRefGoogle Scholar
  142. Çirpanli Y, Bilensoy E, Lale Doğan A, Çaliş S (2009) Comparative evaluation of polymeric and amphiphilic cyclodextrin nanoparticles for effective camptothecin delivery. Eur J Pharm Biopharm 73(1):82–89PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Université de LyonLyonFrance
  2. 2.UMR 5007, Laboratoire D’Automatique et de Génie Des Procédés, LAGEP-CPE-308GUniversité Lyon 1, Villeurbanne, CNRSVilleurbanneFrance
  3. 3.Laboratoire de Pharmacie GaléniqueUniversité de MonastirMonastirTunisia

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