Abstract
In this study, we report the optimization of a solvent evaporation technique for preparing monodisperse poly-(lactide-co-glycolide) (PLGA) nanospheres, from a mixture of solvents composed of ethanol and PVA solution. Various experimental conditions were investigated in order to control the particle size and size distribution of the nanospheres. In addition, nanospheres containing rifampicin (RFP, an antituberculosis drug), were prepared using PLGA of various molecular weights, to study the effects of RFP as a model hydrophobic drug. The results showed that a higher micro-homogenizer stirring rate facilitated the preparation of monodisperse PLGA nanospheres with a low coefficient of variation (~20 %), with sizes below 200 nm. Increasing the PLGA concentration from 0.1 to 0.5 g resulted in an increase in the size of the obtained nanospheres from 130 to 174 nm. The molecular weight of PLGA had little effect on the particle sizes and particle size distributions of the nanospheres. However, the drug loading efficiencies of the obtained RFP/PLGA nanospheres decreased when the molecular weight of PLGA was increased. Based on these experiments, an optimized technique was established for the preparation of monodisperse PLGA nanospheres, using the method developed by the authors.
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Freitas S, Merkle HP, Gander B (2005) Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology. J Control Release 102:313–332
Ito F, Kawakami H (2015) Facile technique for the preparation of monodispersed biodegradable polymer nanospheres using a solvent evaporation method. Colloids Surf A Physicochem Eng Asp 482:734–739
Ito F, Makino K (2004) Preparation and properties of monodispersed rifampicin-loaded poly(lactide-co-glycolide) microspheres. Colloids Surf B Biointerfaces 39:17–21
Ito F, Fujimori H, Makino K (2007) Incorporation of water-soluble drugs in PLGA microspheres. Colloids Surf B Biointerfaces 54:173–178
Ito F, Honnami H, Kawakami H, Kanamura K, Makino K (2008) Preparation and properties of PLGA microspheres containing hydrophilic drugs by SPG (Shirasu porous glass) membrane emulsification technique. Colloids Surf B Biointerfaces 67:20–25
Ito F, Fujimori H, Honnami H, Kawakami H, Kanamura K, Makino K (2009) Study of types and mixture ratio of organic solvent used to dissolve polymers for preparation of drug-containing PLGA microspheres. Eur Polym J 45:658–667
Ito F, Fujimori H, Honnami H, Kawakami H, Kawakami K, Kanamura K, Makino K (2010) Control of drug loading efficiency and drug release behavior in preparation of hydrophilic-drug-containing monodisperse PLGA microspheres. J Mater Sci Mater Med 21:1563–1571
Ito F, Fujimori H, Kawakami H, Kanamura K, Makino K (2011a) Technique to encapsulate a low molecular weight hydrophilic drug in biodegradable polymer particles in a liquid–liquid system. Colloids Surf A Physicochem Eng Asp 384:368–373
Ito F, Kanakubo Y, Murakami Y (2011b) Rapid preparation of monodisperse biodegradable polymer nanospheres using a membrane emulsification technique under low gas pressure. J Polymer Res 18:2077–2085
Ito F, Fujimori H, Kawakami H, Kanamura K, Makino K (2012) Optimized preparation of biodegradable polymer particles encapsulating low-molecular weight hydrophilic drugs. Colloids Surf A Physicochem Eng Asp 402:29–36
Ito F, Takahashi T, Kanamura K, Kawakami H (2013) Possibility for the development of cosmetics with PLGA nanospheres. Drug Dev Ind Pharm 39(5):752–761
Ito F, Fujimori H, Makino K (2014) Preparation of (hydrophilic) INZ/PLGA particles (microcapsules) employing a unique frozen water phase—investigation of optimal formulation. Colloids Surf A Physicochem Eng Asp 443:356–362
Jain RA (2000) The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21:2475–2490
Kawashima Y, Yamamoto H, Takeuchi H, Hino T, Niwa T (1998) Properties of a peptide containing dl-lactide/glycolide copolymer nanospheres prepared by novel emulsion diffusion methods. Eur J Pharm Biopharm 45:41–48
Lamprecht A, Ubrich N, Yamamoto H, Schäfer U, Takeuchi H, Maincent P, Kawashima Y, Lehr CM (2001) Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease. J Pharmacol Exp Ther 299:775–781
Ma GH, Nagai M, Omi S (1999) Preparation of uniform poly (lactide) microspheres by employing the Shirasu Porous Glass (SPG) emulsification technique. Colloids Surf A Physicochem Eng Asp 153:383–394
Makino K, Nakajima T, Shikamura M, Ito F, Ando S, Kochi C, Inagawa H, Soma GI, 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
Ogawa Y, Yamamoto M, Okada H, Yashiki T, Shimamoto T (1988) A new technique to efficiently entrap leuprolide acetate into micro capsules of poly lactic acid or copoly (lactic/glycolic) acid. Chem Pharm Bull 36(3):1095–1103
Okada H (1997) One- and three-month release injectable microspheres of the LH-RH superagonist leuprorelin acetate. Adv Drug Deliv Rev 28:43–70
Shiga K, Muramatsu N, Kondo T (1996) Preparation of poly(D,L-lactide) and copoly (lactide–glycolide) microspheres of uniform size. J Pharm Pharmacol 48:891–895
Stracke F, Weiss B, Lehr C-M, König K, Schaefer UF, Schneider M (2006) Multiphoton microscopy for the investigation of dermal penetration of nanoparticle-borne drugs. J Invest Dermatol 126:2224–2233
Zolnik BS, Burgess DJ (2008) Evaluation of in vivo–in vitro release of dexamethasone from PLGA microspheres. J Control Release 127:137–145
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Ito, F. Optimization of a simple technique for preparation of monodisperse poly(lactide-co-glycolide) nanospheres. J Nanopart Res 18, 262 (2016). https://doi.org/10.1007/s11051-016-3579-7
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DOI: https://doi.org/10.1007/s11051-016-3579-7