Microspheres and microcapsules for protein delivery: Strategies of drug activity retention

Current Pharmaceutical Design

Volumn 19, Issue 35, 2013, Pages 6340-6352

  Wang, Lianyan ^a   Liu, Yuan ^a,b   Zhang, Weifeng ^a,b   Chen, Xiaoming ^a,b   Yang, Tingyuan ^a   Ma, Guanghui ^a  

^a INSTITUTE OF PROCESS ENGINEERING   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

Author keywords

Activity retention; Hydrophilic polymer microspheres; Hydrophobic polymer microcapsules; Protein delivery; Strategies

Indexed keywords

1,6 BIS(4 CARBOXYPHENOXY)HEXANE; 2 HYDROXYPROPYL BETA CYCLODEXTRIN; ALGINIC ACID; BOVINE SERUM ALBUMIN; CHITOSAN; COPOLYMER; DEXTRAN; ENZYME; GROWTH FACTOR; HEMOGLOBIN; HYALURONIC ACID; IMMUNOGLOBULIN G; INSULIN; LYSOZYME; MICROSPHERE; MONOMETHOXYPOLY(ETHYLENE GLYCOL CO LACTIDE); OVALBUMIN; PHARMACEUTICAL VEHICLES AND ADDITIVES; POLY 1,3 BIS(4 CARBOXYPHENOXY)PROPANE CO SEBACIC ACID; POLY(ORTHO ESTER); POLY[1,8 BIS(4 CARBOXYPHENOXY) 3,6 DIOXA OCTANE]; POLYANHYDRIDE; POLYGLACTIN; POLYLACTIDE; POLYMER; PROTEIN; SALCATONIN; STARCH; UNCLASSIFIED DRUG; UNINDEXED DRUG; WATER OIL CREAM;

BIOCOMPATIBILITY; BIODEGRADABILITY; CHEMICAL MODIFICATION; COACERVATION; CROSS LINKING; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG RETENTION; EMULSION; FREEZE DRYING; GELATION; HIGH TEMPERATURE; HUMAN; HYDROPHILICITY; HYDROPHOBICITY; IMMUNOGENICITY; MICROCAPSULE; NONHUMAN; PHASE SEPARATION; PRECIPITATION; PRIORITY JOURNAL; PROCESS OPTIMIZATION; PROTEIN DENATURATION; PROTEIN STABILITY; RECOMBINANT DNA TECHNOLOGY; REVIEW; SHEAR STRESS; SOLID; SOLIDIFICATION; SPRAY DRYING;

ANIMALS; CAPSULES; CHEMISTRY, PHARMACEUTICAL; DELAYED-ACTION PREPARATIONS; DRUG COMPOUNDING; DRUG DELIVERY SYSTEMS; DRUG STABILITY; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; MICROSPHERES; POLYMERS; PROTEINS;

EID: 84887950467     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612811319350010     Document Type: Review

References (129)

1. Bilati U, Allemann E, Doelker E. Strategic approaches for overcoming peptide and protein instability within biodegradable nano-and microparticles. Eur J Pharm Biopharm 2005; 59: 375-88.
2. Sola RJ, Griebenow K. Effects of Glycosylation on the Stability of Protein Pharmaceuticals. J Pharm Sci 2009; 98: 1223-45.
3. Morita T, Sakamura Y, Horikiri Y, et al. Protein encapsulation into biodegradable microspheres by a novel S/O/W emulsion method using poly(ethylene glycol) as a protein micronization adjuvant. J Control Release 2000; 69: 435-44.
4. Yeo Y, Baek N, Park K. Microencapsulation methods for delivery of protein drugs. Biotechnol Bioprocess Eng 2001; 6: 213-30.
5. Peppas NA, Carr DA. Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents. Chem Eng Sci 2009; 64: 4553-65.
6. Yan W, Huang L. Recent advances in liposome-based nanoparticles for antigen delivery. Polym Rev 2007; 47: 329-44.
7. Gaucher G, Satturwar P, Jones M-C, et al. Polymeric micelles for oral drug delivery. Eur J Pharm Biopharm 2010; 76: 147-58.
8. Eyles JE, Carpenter ZC, Alpar HO, et al. Immunological aspects of polymer microsphere vaccine delivery systems. J Drug Target 2003; 11: 509-14.
9. De Temmerman ML, De Vos F, Demeester J, et al. Protein encapsulation in polyelectrolyte microcapsules for antigen delivery. J Control Release 2010; 148: E54-E6.
10. Meng FT, Ma GH, Liu YD, et al. Microencapsulation of bovine hemoglobin with high bio-activity and high entrapment efficiency using a W/O/W double emulsion technique. Colloid Suface B 2004; 33: 177-83.
11. Sood A, Panchagnula R. Peroral route: An opportunity for protein and peptide drug delivery. Chem Rev 2001; 101: 3275-303.
12. del Valle EMM, Galan MA, and Carbonell RG. Drug Delivery Technologies: The Way Forward in the New Decade. Ind Eng Chem Res 2009; 48: 2475-86.
13. Kokai LE, Tan HP, Jhunjhunwala S, et al. Protein bioactivity and polymer orientation is affected by stabilizer incorporation for double-walled microspheres. J Control Release 2010; 141: 168-76.
14. Fu K, Klibanov AM, Langer R. Protein stability in controlledrelease systems. Nat Biotechnol 2000; 18: 24-5.
15. Rathore N, Rajan RS. Current perspectives on stability of protein drug products during formulation, fill and finish operations. Biotechnol Progr 2008; 24: 504-14.
16. van der Walle CF, Sharma G, Kumar MNVR. Current approaches to stabilising and analysing proteins during microen-capsulation in PLGA. Expert Opin Drug Del 2009; 6: 177-86.
17. van de Weert M, Hennink WE, and Jiskoot W. Protein Instability in Poly(Lactic-co-Glycolic Acid) Microparticles. Pharm Res 2000; 17: 1159-67.
18. Tamber H, Johansen P, Merkle HP, et al. Formulation aspects of biodegradable polymeric microspheres for antigen delivery. Adv Drug Delivery Rev 2005; 57: 357-76.
19. Kumar MNVR, Muzzarelli RAA, Muzzarelli C, et al. Chitosan chemistry and pharmaceutical perspectives. Chem Rev 2004; 104: 6017-84.
20. Wang LY, Gu YH, Zhou QZ, et al. Preparation and characterization of uniform-sized chitosan microspheres containing insulin by membrane emulsification and a two-step solidification process. Colloid Suface B 2006; 50: 126-35.
21. Wang LY, Gu YH, Su ZG, et al. Preparation and improvement of release behavior of chitosan microspheres containing insulin. Int J Pharm 2006; 311: 187-95.
22. Yang M, Velaga S, Yamamoto H, et al. Characterisation of salmon calcitonin in spray-dried powder for inhalation-Effect of chitosan. Int J Pharm 2007; 331: 176-81.
23. Boonyo W, Junginger HE, Waranuch N, et al. Chitosan and trimethyl chitosan chloride (TMC) as adjuvants for inducing immune responses to ovalbumin in mice following nasal administration. J Control Release 2007; 121: 168-75.
24. Goh CH, Heng PWS, and Chan LW. Alginates as a useful natural polymer for microencapsulation and therapeutic applications. Carbohydr Polym 2012; 88: 1-12.
25. Zhang Y, Wei W, Lv P, et al. Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin. Eur J Pharm Biopharm 2011; 77: 11-9.
26. Ribeiro AJ, Silva C, Ferreira D, et al. Chitosan-reinforced alginate microspheres obtained through the emulsification/internal gelation technique. Eur J Pharm Sci 2005; 25: 31-40.
27. Yuan WE, Geng Y, Wu F, et al. Preparation of polysaccharide glassy microparticles with stabilization of proteins. Int J Pharm 2009; 366: 154-9.
28. Shu SJ, Zhang XG, Wu ZM, et al. Delivery of protein drugs using nanoparticles self-assembled from dextran sulfate and quaternized chitosan. J Control Release 2011; 152: E170-E2.
29. Rydén L and Edman P. Effect of polymers and microspheres on the nasal absorption of insulin in rats. Int J Pharm 1982; 83: 1-10.
30. Pereswetoff-Morath L and Edman P. Dextran microspheres as a potential nasal drug delivery system for insulin-in vitro and in vivo properties. Int J Pharm 1995; 124: 37-44.
31. Wei Q, Ai H, and Gu Z. Matrix polyelectrolyte capsules based on polysaccharide/MnCO3 hybrid microparticle templates. Colloid Suface B 2011; 85: 63-72.
32. Surendrakumar K, Martyn GP, Hodgers ECM, et al. Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs. J Control Release 2003; 91: 385-94.
33. Kim SJ, Hahn SK, Kim MJ, et al. Development of a novel sustained release formulation of recombinant human growth hormone using sodium hyaluronate microparticles. J Control Release 2005; 104: 323-35.
34. Hahn SK, Kim SJ, Kim MJ, et al. Characterization and In vivo Study of Sustained-Release Formulation of Human Growth Hormone Using Sodium Hyaluronate. Pharm Res 2004; 21: 1374-81.
35. Farraj NF, Johansen BR, Davis SS, et al. Nasal administration of insulin using bioadhesive microspheres as a delivery system. J Control Release 1990; 13: 253-61.
36. Björk E and Edman P. Degradable starch microspheres as a nasal delivery system for insulin. Int J Pharm 1988; 47: 233-8.
37. Illum L, Farraj NF, Davis SS, et al. Investigation of the nasal absorption of biosynthetic human growth hormone in sheep-use of a bioadhesive microsphere delivery system. Int J Pharm 1990; 63: 207-11.
38. Dai CY, Wang BC, and Zhao HW. Microencapsulation peptide and protein drugs delivery system. Colloid Suface B 2005; 41: 117-20.
39. Dash M, Chiellini F, Ottenbrite RM, et al. Chitosan-A versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci 2011; 36: 981-1014.
40. Wu XS. Synthesis and properties of biodegradable lactic/glycolic acid polymers. In: Wise DL, Ed. Encyclopedic Handbook of Biomaterials and Bioengineering. New York: Marcel Dekker 1995; pp. 1015-1054.
41. Sinha VR and Trehan A. Biodegradable microspheres for protein delivery. J Control Release 2003; 90: 261-80.
42. Alsarra IA, Neau SH, and Howard MA. Effects of preparative parameters on the properties of chitosan hydrogel beads containing Candida rugosa lipase. Biomaterials 2004; 25: 2645-55.
43. Makhlof A, Tozuka Y, and Takeuchi H. Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery. Eur J Pharm Sci 2011; 42: 445-51.
44. De Koker S, De Cock LJ, Rivera-Gil P, et al. Polymeric multilayer capsules delivering biotherapeutics. Adv Drug Delivery Rev 2011; 63: 748-61.
45. Wang LY, Wu J, Wei W, et al. Preparation and Applications of Chitosan Microsphere. In: Jayakumar R, Prabaharan M. Eds. Current Research and Developments on Chitin and Chitosan in Biomaterial Science. Kerala: Research Signpost 2008; pp. 143-163.
46. Jose S, Fangueiro JF, Smitha J, et al. Cross-linked chitosan microspheres for oral delivery of insulin: Taguchi design and in vivo testing. Colloid Suface B 2012; 92: 175-9.
47. Sivakumar SM, Sukumaran N, Nirmala L, et al. Immunopotentiation of Hepatitis B Vaccine Using Biodegradable Polymers as an Adjuvant. J Microbiol Immunol 2010; 43: 265-70.
48. Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 2000; 21: 2475-90.
49. Nihant N, Grandfils C, Jérôme R, et al. Microencapsulation by coacervation of poly(lactide-co-glycolide) IV. Effect of the processing parameters on coacervation and encapsulation. J Control Release 1995; 35: 117-25.
50. Nihant N, Stassen S, Grandfils C, et al. Microencapsulation by coacervation of poly(lactide-co-glycolide). III. Characterization of the final microspheres. Polym Int 1994; 34: 289-99.
51. Celik O and Akbuga J. Preparation of superoxide dismutase loaded chitosan microspheres: Characterization and release studies. Eur J Pharm Biopharm 2007; 66: 42-7.
52. Ozbas-Turan S, Akbuga J, and Aral C. Controlled release of interleukin-2 from chitosan microspheres. J Pharm Sci 2002; 91: 1245-51.
53. Adamiec J and Modrzejewska Z. Some structural properties of spray-dried chitosan microgranules. Drying Technol 2005; 23: 1601-11.
54. Harikarnpakdee S, Lipipun V, Sutanthavibul N, et al. Spray-dried mucoadhesive microspheres: Preparation and transport through nasal cell monolayer. AAPS PharmSciTech 2006; 7(1): E12.
55. Grenha A, Seijo B, Serra C, et al. Chitosan nanoparticle-loaded mannitol microspheres: Structure and surface characterization. Biomacromolecules 2007; 8: 2072-9.
56. Nunthanid J, Laungtana-Anan A, Sriamornsak P, et al. Characterization of chitosan acetate as a binder for sustained release tablets. J Control Release 2004; 99: 15-26.
57. Xu Q, Guo L, Gu X, et al. Prevention of colorectal cancer liver metastasis by exploiting liver immunity via chitosan-TPP/nanoparticles formulated with IL-12. Biomaterials 2012; 33: 3909-18.
58. De Koker S, Hoogenboom R, and De Geest BG. Polymeric multilayer capsules for drug delivery. Chem Soc Rev 2012; 41: 2867-84.
59. Suslick KS and Grinstaff MW. Protein Microencapsulation of Nonaqueous Liquids. J Am Chem Soc 1990; 112: 7807-9.
60. Albasarah YY, Somavarapu S, and Taylor KMG. Stabilizing protein formulations during air-jet nebulization. Int J Pharm 2010; 402: 140-5.
61. Zhong MT, Ming XW, Su PW, et al. Effects of ultrasound and additives on the function and structure of trypsin. Ultrason Sonochem 2004; 11: 399-404.
62. Sehgal C, Sutherland RG, and Verrall RE. Sonoluminescence of No-Saturated and No2-Saturated Water as a Probe of Acoustic Cavitation. J Phys Chem 1980; 84: 396-401.
63. Barteri M, Fioroni M, and Gaudiano MC. Oxidation of Fe(II) horse heart cytochrome c by ultrasound waves. Biochimica et Biophysica Acta (BBA)-Protein Structure and Molecular Enzymology 1996; 1296: 35-40.
64. Scharnagl C, Reif M, and Friedrich J. Stability of proteins: Temperature, pressure and the role of the solvent. Biochimica Et Biophysica Acta-Proteins and Proteomics 2005; 1749: 187-213.
65. Gekko K and Timasheff SN. Thermodynamic and Kinetic Examination of Protein Stabilization by Glycerol. Biochemistry 1981; 20: 4677-86.
66. Schmidt A, Schumacher JT, Reichelt J, et al. Mechanistic and molecular investigations on stabilization of horseradish peroxidase C. Anal Chem 2002; 74: 3037-45.
67. Cho HJ, Balakrishnan P, Chung SJ, et al. Evaluation of protein stability and in vitro permeation of lyophilized polysaccharidesbased microparticles for intranasal protein delivery. Int J Pharm 2011; 416: 77-84.
68. Brewster ME, Hora MS, Simpkins JW, et al. Use of 2-Hydroxypropyl-β-cyclodextrin as a Solubilizing and Stabilizing Excipient for Protein Drugs. Pharm Res 1991; 8: 792-5.
69. Haeberlin B, Gengenbacher T, Meinzer A, et al. Cyclodextrins-Useful excipients for oral peptide administration? Int J Pharm 1996; 137: 103-10.
70. Li T, Longobardi L, Granero-Molto F, et al. Use of glycol chitosan modified by 5β-cholanic acid nanoparticles for the sustained release of proteins during murine embryonic limb skeletogenesis. J Control Release 2010; 144: 101-8.
71. Amidi M, Romeijn SG, Borchard G, et al. Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. J Control Release 2006; 111: 107-16.
72. Chen F, Zhang ZR, and Huang Y. Evaluation and modification of N-trimethyl chitosan chloride nanoparticles as protein carriers. Int J Pharm 2007; 336: 166-73.
73. Emami J, Hamishehkar H, Najafabadi AR, et al. A novel approach to prepare insulin-loaded poly(lactic-co-glycolic acid) microcapsules and the protein stability study. J Pharm Sci 2009; 98: 1712-31.
74. Lopac SK, Torres MP, Wilson-Welder JH, et al. Effect of polymer chemistry and fabrication method on protein release and stability from polyanhydride microspheres. J Biomed Mater Res Part B 2009; 91B: 938-47.
75. Manoharan C and Singh J. Evaluation of polyanhydride microspheres for basal insulin delivery: Effect of copolymer composition and zinc salt on encapsulation, in vitro release, stability, in vivo absorption and bioactivity in diabetic rats. J Pharm Sci 2009; 98: 4237-50.
76. Soppimath KS, Aminabhavi TM, Kulkarni AR, et al. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 2001; 70: 1-20.
77. Park W and Na K. Dermatan sulfate as a stabilizer for protein stability in poly(lactide-co-glycolide) depot. Biotechnol Bioprocess Eng 2009; 14: 668-74.
78. Determan AS, Trewyn BG, Lin VSY, et al. Encapsulation, stabilization, and release of BSA-FITC from polyanhydride microspheres. J Control Release 2004; 100: 97-109.
79. Determan AS, Wilson JH, Kipper MJ, et al. Protein stability in the presence of polymer degradation products: Consequences for controlled release formulations. Biomaterials 2006; 27: 3312-20.
80. Aubert-Pouëssel A, Bibby DC, Venier-Julienne M-C, et al. A Novel < > in vitro Delivery System for Assessing the Biological Integrity of Protein upon Release from PLGA Microspheres. Pharm Res 2002; 19: 1046-51.
81. Srinivasan C, Katare YK, Muthukumaran T, et al. Effect of additives on encapsulation efficiency, stability and bioactivity of entrapped lysozyme from biodegradable polymer particles. J Microencapsulation 2005; 22: 127-38.
82. Castellanos IJ, Flores G, and Griebenow K. Effect of cyclodextrins on alpha-chymotrypsin stability and loading in PLGA microspheres upon S/O/W encapsulation. J Pharm Sci 2006; 95: 849-58.
83. Perez C and Griebenow K. Effect of salts on lysozyme stability at the water-oil interface and upon encapsulation in poly(lactic-coglycolic) acid microspheres. Biotechnol Bioeng 2003; 82: 825-32.
84. Castellanos IJ, Al-Azzam W, and Griebenow K. Effect of the covalent modification with poly(ethylene glycol) on alphachymotrypsin stability upon encapsulation in poly(lactic-coglycolic) microspheres. J Pharm Sci 2005; 94: 327-40.
85. Castellanos IJ, Flores G, and Griebenow K. Effect of the molecular weight of poly(ethylene glycol) used as emulsifier on alphachymotrypsin stability upon encapsulation in PLGA microspheres. J Pharm Pharmacol 2005; 57: 1261-9.
86. Perugini P, Genta I, Pavanetto F, et al. Evaluation of enzyme stability during preparation of polylactide-co-glycolide microspheres. J Microencapsulation 2002; 19: 591-602.
87. van der Walle CF, Sharma G, and Ravi Kumar M. Current approaches to stabilising and analysing proteins during microencapsulation in PLGA. Expert Opin Drug Del 2009; 6: 177-86.
88. Kang F, Jiang G, Hinderliter A, et al. Lysozyme Stability in Primary Emulsion for PLGA Microsphere Preparation: Effect of Recovery Methods and Stabilizing Excipients. Pharm Res 2002; 19: 629-33.
89. Pérez C and Griebenow K. Improved activity and stability of lysozyme at the water/CH2CI2 interface: enzyme unfolding and aggregation and its prevention by polyols. J Pharm Pharmacol 2001; 53: 1217-26.
90. Geng Y, Yuan W, Wu F, et al. Formulating erythropoietin-loaded sustained-release PLGA microspheres without protein aggregation. J Control Release 2008; 130: 259-65.
91. Heffernan MJ, Kasturi SP, Yang SC, et al. The stimulation of CD8+ T cells by dendritic cells pulsed with polyketal microparticles containing ion-paired protein antigen and poly(inosinic acid)-poly(cytidylic acid). Biomaterials 2009; 30: 910-8.
92. Rosa GD, Iommelli R, La Rotonda MI, et al. Influence of the coencapsulation of different non-ionic surfactants on the properties of PLGA insulin-loaded microspheres. J Control Release 2000; 69: 283-95.
93. K. F. Pistel TK. Effects of salt addition on the microencapsulation of proteins using W/O/W double emulsion technique. J Microencapsulation 2000; 17: 467-83.
94. Bouillot P, Ubrich N, Sommer F, et al. Protein encapsulation in biodegradable amphiphilic microspheres. Int J Pharm 1999; 181: 159-72.
95. Li X, Deng X, Yuan M, et al. Investigation on process parameters involved in preparation of poly-dl-lactide-poly(ethylene glycol) microspheres containing Leptospira Interrogans antigens. Int J Pharm 1999; 178: 245-55.
96. Freytag T, Dashevsky A, Tillman L, et al. Improvement of the encapsulation efficiency of oligonucleotide-containing biodegradable microspheres. J Control Release 2000; 69: 197-207.
97. Johansen P, Men Y, Audran R, et al. Improving Stability and Release Kinetics of Microencapsulated Tetanus Toxoid by Co-Encapsulation of Additives. Pharm Res 1998; 15: 1103-10.
98. Kim TH, Jiang HH, Park CW, et al. PEGylated TNF-related apoptosis-inducing ligand (TRAIL)-loaded sustained release PLGA microspheres for enhanced stability and antitumor activity. J Control Release 2011; 150: 63-9.
99. Ibrahim MA. Assessment of insulin stability inside diblock copolymer PEG-PLA microspheres. Sci Pharm 2010; 78: 493-505.
100. Giteau A, Venier-Julienne M-C, Marchal S, et al. Reversible protein precipitation to ensure stability during encapsulation within PLGA microspheres. Eur J Pharm Biopharm 2008; 70: 127-36.
101. Diwan M and Park TG. Pegylation enhances protein stability during encapsulation in PLGA microspheres. J Control Release 2001; 73: 233-44.
102. Wolf M, Wirth M, Pittner F, et al. Stabilisation and determination of the biological activity of L-asparaginase in poly(D, L-lactide-coglycolide) nanospheres. Int J Pharm 2003; 256: 141-52.
103. Sanchez A, Tobio M, Gonzalez L, et al. Biodegradable micro-and nanoparticles as long-term delivery vehicles for interferon-alpha. Eur J Pharm Sci 2003; 18: 221-9.
104. Li XH, Zhang YH, Yan RH, et al. Influence of process parameters on the protein stability encapsulated in poly-DL-lactidepoly(ethylene glycol) microspheres. J Control Release 2000; 68: 41-52.
105. Pean JM, Boury F, Venier-Julienne MC, et al. Why does PEG 400 co-encapsulation improve NGF stability and release from PLGA biodegradable microspheres? Pharm Res 1999; 16: 1294-9.
106. He JT, Su HB, Li GP, et al. Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres. Int J Pharm 2006; 309: 101-8.
107. Cleland JL and Jones AJS. Stable formulations of recombinant human growth hormone and interferon-gamma for microencapsulation in biodegradable microspheres. Pharm Res 1996; 13: 1464-75.
108. Park W and Na K. Polyelectrolyte complex of chondroitin sulfate and peptide with lower pI value in poly(lactide-co-glycolide) microsphere for stability and controlled release. Colloid Suface B 2009; 72: 193-200.
109. Taluja A and Bae YH. Role of a novel excipient poly(ethylene glycol)-b-poly(L-histidine) in retention of physical stability of insulin at aqueous/organic interface. Mol Pharmaceutics 2007; 4: 561-70.
110. Perez C, Castellanos IJ, Costantino HR, et al. Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers. J Pharm Pharmacol 2002; 54: 301-13.
111. Sah H. Protein behavior at the water/methylene chloride interface. J Pharm Sci 1999; 88: 1320-5.
112. He J, Feng M, Zhou X, et al. Stabilization and encapsulation of recombinant human erythropoietin into PLGA microspheres using human serum albumin as a stabilizer. Int J Pharm 2011; 416: 69-76.
113. Castellanos IJ, Crespo R, and Griebenow K. Poly(ethylene glycol) as stabilizer and emulsifying agent: a novel stabilization approach preventing aggregation and inactivation of proteins upon encapsulation in bioerodible polyester microspheres. J Control Release 2003; 88: 135-45.
114. Aubert-Pouessel A, Bibby DC, Venier-Julienne MC, et al. A novel in vitro delivery system for assessing the biological integrity of protein upon release from PLGA microspheres. Pharm Res 2002; 19: 1046-51.
115. Diwan M and Park TG. Stabilization of recombinant interferonalpha by pegylation for encapsulation in PLGA microspheres. Int J Pharm 2003; 252: 111-22.
116. Bouillot P, Ubrich N, Sommer F, et al. Protein encapsulation in biodegradable amphiphilic microspheres. Int J Pharm 1999; 181: 159-72.
117. Wan JP, Yang YY, Chung TS, et al. POE-PEG-POE triblock copolymeric microspheres containing protein-II. Polymer erosion and protein release mechanism. J Control Release 2001; 75: 129-41.
118. Yuan W, Geng Y, Wu F, et al. Preparation of polysaccharide glassy microparticles with stabilization of proteins. Int J Pharm 2009; 366: 154-9.
119. Lee ES, Kwon MJ, Lee H, et al. Stabilization of protein encapsulated in poly(lactide-co-glycolide) microspheres by novel viscous S/W/O/W method. Int J Pharm 2007; 331: 27-37.
120. Zolnik BS and Burgess DJ. Effect of acidic pH on PLGA microsphere degradation and release. J Control Release 2007; 122: 338-44.
121. Zhu GZ, Mallery SR, and Schwendeman SP. Stabilization of proteins encapsulated in injectable poly (lactide-co-glycolide). Nat Biotechnol 2000; 18: 52-7.
122. Nochi T, Yuki Y, Takahashi H, et al. Nanogel antigenic proteindelivery system for adjuvant-free intranasal vaccines. Nat Mater 2010; 9: 572-8.
123. Wei Y, Wang Y-X, Wang W, et al. mPEG-PLA microspheres with narrow size distribution increase the controlled release effect of recombinant human growth hormone. J Mater Chem 2011; 21: 12691-9.
124. Staquicini FI, Ozawa MG, Moya CA, et al. Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma. J Clin Invest 2011; 121: 161-73.
125. Crotts G and Park TG. Stability and release of bovine serum albumin encapsulated within poly(d, l-lactide-co-glycolide) microparticles. J Control Release 1997; 44: 123-34.
126. Jiang G, Woo BH, Kang F, et al. Assessment of protein release kinetics, stability and protein polymer interaction of lysozyme encapsulated poly(d, l-lactide-co-glycolide) microspheres. J Control Release 2002; 79: 137-45.
127. Sasiak AB, Bolgiano B, Crane DT, et al. Comparison of in vitro and in vivo methods to study stability of PLGA microencapsulated tetanus toxoid vaccines. Vaccine 2000; 19: 694-705.
128. Igartua M, Hernández RM, Esquisabel A, et al. Stability of BSA encapsulated into PLGA microspheres using PAGE and capillary electrophoresis. Int J Pharm 1998; 169: 45-54.
129. Péan J-M, Venier-Julienne M-C, Boury F, et al. NGF release from poly(d, l-lactide-co-glycolide) microspheres. Effect of some formulation parameters on encapsulated NGF stability. J Control Release 1998; 56: 175-87.