Abstract
The star-shaped poly(l-lactide) (s-PLLA) was synthesized via ring-opening polymerization of l-lactide, with xylitol as a multifunctional initiator and stannous octoate as a catalyst. The structures of s-PLLA were characterized by 1H NMR spectroscopy, while the molecular weight (M w) and polydispersity index were determined by gel permeation chromatography. Bovine serum albumin (BSA) loaded s-PLLA microspheres were fabricated by a water–oil–water (W 1/O/W 2) double-emulsion solvent evaporation method. The morphology, drug encapsulation efficiency (EE), and in vitro release behavior of the prepared microspheres were studied in detail. Results indicated that the average diameters of s-PLLA microspheres could be controlled between 7 and 15 µm by varying the s-PLLA’s concentration or M w, and the drug encapsulation efficiency of BSA-loaded microspheres were 10–42%. The in vitro study shows that the BSA-loaded microspheres prepared by high molecular weight s-PLLA had a slow cumulative release behavior in phosphate buffer saline (PBS, pH 7.4) and the release process followed the Baker–Lonsdale equation. Present work supposes that the synthesized s-PLLA is a good candidate for drug delivery.
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References
Samadi N, Abbadessa A, Di Stefano A, van Nostrum CF, Vermonden T, Rahimian S (2013) The effect of lauryl capping group on protein release and degradation of poly(d,l-lactic-co-glycolic acid) particles. J Control Release 172:436–443
Dev A, Binulal NS, Anitha A, Nair SV, Furuike T, Tamura H (2010) Preparation of poly(lactic acid)/chitosan nanoparticles for anti-HIV drug delivery applications. Carbohydr Polymer 80:833–838
Ding N, Shentu BQ, Pan PJ, Shan GR, Bao YZ, Weng ZX (2013) Synthesis and crystallization of poly(vinyl acetate)-g-poly(l-lactide) graft copolymer with controllable graft density. Ind Eng Chem Res 52:12897–12905
Bagheri M, Motirasoul F (2013) Synthesis, characterization, and micellization of cholesteryl-modified amphiphilic poly(l-lactide)-block-poly(glycidyl methacrylate) as a nanocarrier for hydrophobic drugs. J Polym Res 20:591–599
Chen Y, Yang Z, Liu C, Wang C, Zhao S, Yang J (2013) Synthesis, characterization, and evaluation of paclitaxel loaded in six-arm star-shaped poly(lactic-co-glycolic acid). Int J Nanomed 8:4315–4326
Ristić IS, Marinović-Cincović M, Cakić SM, Tanasić LM, Budinski-Simendić JK (2013) Synthesis and properties of novel star-shaped polyesters based on l-lactide and castor oil. Polym Bull 70:1723–1738
Zhang X, Wang C, Fang S, Sun J, Li C, Hu Y (2012) Synthesis and characterization of well-defined star PLLA with a POSS core and their microspheres for controlled release. Colloid Polymer Sci 291:789–803
Sakamoto Y, Tsuji H (2013) Crystallization behavior and physical properties of linear 2-arm and branched 4-arm poly(l-lactide)s: effects of branching. Polymer 54:2422–2434
Dai X-H, Jin H, Cai M-H, Zhou Z-P, Pan J-M, Yan Y-S, Sun L (2015) Fabrication of thermosensitive, star-shaped poly(l-lactide)-block-poly (N-iso propyl acryl- amide) copolymers with porphyrin core for photodynamic therapy. React Funct Polym 89:9–17
Tsuji H, Hayashi T (2015) Hydrolytic degradation and crystallization behavior of linear 2-armed and star-shaped 4-armed poly(l-lactide)s: effects of branching architecture and crystallinity. J Appl Polym Sci 132:2001–2013
Gaignaux A, Reeff J, Siepmann F, Siepmann J, De Vriese C, Goole J (2012) Development and evaluation of sustained-release clonidine-loaded PLGA microparticles. Int J Pharm 437:20–28
Rasal RM, Janorkar AV, Hirt DE (2010) Poly(lactic acid) modifications. Prog Polym Sci 35:338–356
Wang Z (2010) Effects of the process parameters on the initial burst release of poly (lactide-co-glycolide) microspheres containing bovine serum albumin by the double-emulsion solvent evaporation/extraction method. J Appl Polym Sci 115:2599–2608
Chandy T, Das GS, Wilson RF et al (2002) Development of polylactide microspheres for protein encapsulation and delivery. J Appl Polym Sci 86:1285–1295
Freitas MN, Marchetti JM (2005) Nimesulide PLA microspheres as a potential sustained release system for the treatment of inflammatory diseases. Int J Pharm 295:201–211
Teng LJ, Nie WY, Zhou YF, Song LY, Chen PP (2015) Synthesis and characterization of star-shaped PLLA with sorbitol as core and its microspheres application in controlled drug release. J Appl Polym Sci 27:132–137
Mosley GL, Yamanishi CD, Kamei DT (2013) Mathematical modeling of vesicle drug delivery systems 1: vesicle formation and stability along with drug loading and release. Jala-Jlab Autom 18:34–45
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
Bale SS, Kwon SJ, Shah DA, Banerjee A, Dordick JS, Kane RS (2010) Nanoparticle-mediated cytoplasmic delivery of proteins to target cellular machinery. Am Chem Soc Nanosci 4:1493–1500
Vermonden T, Censi R, Hennink WE (2012) Hydrogels for protein delivery. Chem Rev 112:2853–2888
Ji YJ, Nguyen HH, Paik SYR et al (2011) Preparation of size-controlled bovine serum albumin (BSA) nanoparticles by a modified desolvation method. Food Chem 127:1892–1898
van de Weert M, Hennink WE, Jiskoot W (2000) Protein instability in poly(lactic-co-glycolic acid) microparticles. Pharm Res 17:1159–1167
Ouyang CP, Liu Q, Zhao SX, Ma GL, Zhang ZP, Song CX (2012) Synthesis and characterization of star-shaped poly (lactide-co-glycolide) and its drug-loaded microspheres. Polym Bull 68:27–36
Maa YF, Hsu CC (1997) Effect of primary emulsions on microsphere size and protein-loading in the double emulsion process. J Microencapsul 14:225–241
Zhao YM, Wang ZY, Yang F (2005) Characterization of poly(d,l-lactic acid) synthesized by direct melt polymerization and its application in Chinese traditional medicine compound prescription microspheres. J Appl Polym Sci 97:195–200
Oledzka E (2013) Synthesis of genistein-containing star-shaped homo and copolyesters by the ring-opening polymerization. Polym Bull 70:2587–2597
Primard C, Poecheim J, Heuking S, Sublet E, Esmaeili F, Borchard G (2013) Multifunctional PLGA-based nanoparticles encapsulating simultaneously hydrophilic antigen and hydrophobic immunomodulator for mucosal immunization. Mol Pharmacol 10:2996–3004
Azizi M, Farahmandghavi F, Joghataei M, Zandi M, Imani M, Bakhtiary M (2013) Fabrication of protein-loaded PLGA nanoparticles: effect of selected formulation variables on particle size and release profile. J Polym Res 20:111–114
Chitkara D, Kumar N (2013) BSA-PLGA-based core-shell nanoparticles as carrier system for water-soluble drugs. Pharm Res 30:2396–2409
Wang Y, Yang X, Liu W, Zhang F, Cai Q, Deng X (2013) Controlled release behaviour of protein-loaded microparticles prepared via coaxial or emulsion electrospray. J Microencapsul 30:490–497
Siepmann J, Siepmann F (2008) Mathematical modeling of drug delivery. Int J Pharm 364:328–343
Siepmann J, Siepmann F (2012) Modeling of diffusion controlled drug delivery. J Control Release 161:351–362
Regnier-Delplace C, du Boullay OT, Siepmann F, Martin-Vaca B, Degrave N, Demonchaux P (2013) PLGA microparticles with zero-order release of the labile anti-Parkinson drug apomorphine. Int J Pharm 443:68–79
Teng L, Nie W, Zhou Y, Chen P (2015) Synthesis and characterization of star-shaped poly(l-lactide)s with an erythritol core and evaluation of their rifampicin-loaded microspheres for controlled drug delivery. Polym Bull 73:97–112
Zou J, Chen X, Shu Y, Zhou H, Huang F (2011) Synthesis, characterization of star-shaped copolymers of l-lactide and epoxidized soybean oil. Polym Bull 66:315–326
Trindade RA, Kiyohara PK, de Araujo PS, da Costa MHB (2012) PLGA microspheres containing bee venom proteins for preventive immunotherapy. Int J Pharm 423:124–133
Yuan MW, He ZG, Li HL, Jiang L, Yuan ML (2014) Synthesis and characterization of star polylactide by ring-opening polymerization of l-lactic acid O-carboxyanhydride. Polym Bull 71:1331–1347
Arvanitoyannis I, Nakayama A, Psomiadou E, Kawasaki N, Yamamoto N (1996) Synthesis and degradability of a novel aliphatic polyester based on l -lactide and sorbitol: 3. Polymer 37:651–660
Ma GL, Zhang C, Zhang LH, Sun HF, Song CX, Wang C (2016) Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery. J Mater Sci Mater Med 27:172–1715
Chaisri W, Ghassemi AH, Hennink WE, Okonogi S (2011) Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters. Colloid Surf B Biointerface 84:508–514
Samadi N, van Nostrum CF, Vermonden T, Amidi M, Hennink WE (2013) Mechanistic studies on the degradation and protein release characteristics of poly(lactic-co-glycolic-co-hydroxymethylglycolic acid) nanospheres. Biomacro- molecules 14:1044–1053
Zeng XW, Tao W, Mei L, Huang LG, Tan CY, Feng SS (2013) Cholic acid-functionalized nanoparticles of star-shaped PLGA-vitamin E TPGS copolymer for docetaxel delivery to cervical cancer. Biomaterials 34:6058–6067
Diab R, Brillault J, Bardy A, Gontijo AVL, Olivier JC (2012) Formulation and in vitro characterization of inhalable polyvinyl alcohol-free rifampicin-loaded PLGA microspheres prepared with sucrose palmitate as stabilizer: efficiency for ex vivo alveolar macrophage targeting. Int J Pharm 436:833–839
Soriano I, Llabres M, Evora C (1995) Release control of albumin from polylactic acid microspheres. Int J Pharm 125:223–230
Narasimhan B (2001) Mathematical models describing polymer dissolution: consequences for drug delivery. Adv Drug Deliv Rev 48:195–210
Acknowledgements
This work was financed by the National Natural Science Foundation of China (Grant No. 51403003), Anhui Provincial Natural Science Foundation (1508085QE105), Scientific Research Fund of Anhui Provincial Education Department (KJ2016A791, KJ2017A030), Postdoctoral Science Foundation of China (01001419) and the 211 Project of Anhui University.
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Ding, A., Teng, L., Zhou, Y. et al. Synthesis and characterization of bovine serum albumin-loaded microspheres based on star-shaped PLLA with a xylitol core and their drug release behaviors. Polym. Bull. 75, 2917–2931 (2018). https://doi.org/10.1007/s00289-017-2197-6
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DOI: https://doi.org/10.1007/s00289-017-2197-6