Oral delivery system for peptides and proteins: II. Application of microencapsulation methods;Administração oral de peptídeos e proteinas: II. Aplicação de métodos de microencapsulação

Revista Brasileira de Ciencias Farmaceuticas/Brazilian Journal of Pharmaceutical Sciences

Volumn 39, Issue 1, 2003, Pages 1-20

  Silva, Catarina ^a   Ribeiro, António ^b   Ferreira, Domingos ^c   Veiga, Francisco ^a  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b Inst Sup da Cie da Saude do Norte   (Portugal)

^c UNIVERSITY OF PORTO   (Portugal)

Author keywords

Microencapsulation; Natural polymers; Oral administration; Peptide drugs

Indexed keywords

PEPTIDE; POLYMER; PROTEIN; SOLVENT;

ANALYTIC METHOD; BIODEGRADABILITY; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG FORMULATION; EMULSION; HIGH TEMPERATURE; MICROENCAPSULATION; PH MEASUREMENT; PHYSICAL CHEMISTRY; POLYMERIZATION; REVIEW;

EID: 0041425278     PISSN: 15169332     EISSN: None     Source Type: Journal    
DOI: 10.1590/s1516-93322003000100002     Document Type: Review

References (110)

1. AFTABROUCHAD, C.; DOELKER, E. Preparation methods for biodegradable microparticles loaded with water-soluble drugs. STP Pharma Sci., Paris, v. 2, p. 365-380, 1992.
2. AGARWAL, V.; REDDY, I. K.; KHAN, M. A. Polymethyacrylate based microparticulates of insulin for oral delivery: Preparation and in vitro dissolution stability in the presence of enzyme inhibitors. Int. J. Pharm., Amsterdam, v. 225, p. 31-39, 2001.
3. AIEDEH, K.; GIANASI, E.; ORIENTI, I.; ZECCHI, V. Chitosan microcapsules as controlled release systems for insulin. J. Microencapsul., London, v. 14, p. 567-576, 1997.
4. ALLÉMAN, E.; GURNY, R.; DOELKER, E. Drug-loaded nanoparticles - preparation methods and drug targeting issues. Eur. J. Pharm. BioPharm., Stuttgart, v. 39, p. 173-191, 1993.
5. ALLEMANN, E.; LEROUX, J. C.; GURNY, R. Polymeric nano- and microparticles for the oral delivery of peptides and peptidomimetics. Adv. Drug Deliv. Rev., Amsterdam, v. 34, p. 171-189, 1998.
6. ALPAR, H. O.; EYLES, J. E.; WILLIAMSON, E. D. Oral and nasal immunization with microencapsulated clinically relevant proteins. STP Pharma Sci., Paris, v. 8, p. 31-39, 1998.
7. ARSHADY, R. Albumin microspheres and microcapsules: methodology of manufacturing techniques. J. Control Release, Amsterdam, v. 14, p. 111-131, 1990.
8. ARSHADY, R. Preparation of biodegradable microspheres and microcapsules. Part 2. Polyactides and related polyesters. J. Controlled Release, Amsterdam, v. 17, p. 1-21, 1991.
9. BAKAN, J. A. Microencapsulation. In: SWARBRICK, J., BOYLAN, J. C., eds. Encyclopedia of Pharmaceutical technology. New York: Marcel Dekker, 1994. v. 9., p. 423-441.
10. BERNKOP-SCHNURCH, A. The use of inhibitory agents to overcome the enzymatic barrier to perorally administered therapeutic peptides and proteins. J. Control Release, Amsterdam, v. 52, p. 1-16, 1998.
11. BLANCO-PRIETO, M. J.; FATTAL, E.; PUISIEUX, F.; COUVREUR, P. Nouvelles approches pour l'encapsulation de peptides au sein de microspheres de PLG. Ann. Pharm. Fr., Paris, v. 56, p. 256-263, 1998.
12. BODMEIER, R.; CHEN, H. Preparation of biodegradable poly(+-)lactide microparticles using a spray-drying technique. J. Pharm. Pharmacol., London, v. 40, p. 754-777, 1988.
13. BOWERSOCK, T. L.; HOGENESCH, H.; SUCKOW, M.; PORTER, R. E.; JACKSON, R.; PARK, H.; PARK, K. Oral vaccination with alginate microsphere systems. J. Control Release, Amsterdam, v. 39, p. 209-220, 1996.
14. BUNDGAARD, H. The utility of the prodrug approach to improve peptide absorption. J. Control Release, Amsterdam, v. 21, p. 63-72, 1992.
15. BURGESS, D. J.; HICKEY, A. J. Microsphere technology and applications. In: SWARBRICK, J.; BOYLAN, J. C., eds. Encyclopedia of Pharmaceutical technology. New York: Marcel Dekker, 1994. v. 10, p. 1-29.
16. BURKE, P. A. Controlled release protein therapeutics: Effects of process and formulation on stability. In: WISE, D. L., ed. Handbook of Pharmaceutical controlled release technology. New York: Marcel-Dekker, 2000. p. 661-692.
17. CARINO, G. P.; JACOB, J. S.; MATHIOWITZ, E. Nanosphere based oral insulin delivery. J. Control Release, Amsterdam, v. 65, p. 261-269, 2000.
18. CARINO, G. P.; MATHIOWITZ, E. Oral insulin delivery. Adv. Drug Deliv. Rev., Amsterdam, v. 35, p. 249-257, 1999.
19. CARRASQUILLO, K. G.; CARRO, J. C.; ALEJANDRO, A.; TORO, D. D.; GRIEBENOW, K. Reduction of structural perturbations in bovine serum albumin by non-aqueous microencapsulation. J. Pharm. Pharmacol, London, v. 53, p. 115-120, 2001.
20. CASTELLANOS, I. J.; CARRASQUILLO, K. G.; LOPEZ, J.; ALVAREZ, M.; GRIEBENOW, K. Encapsulation of bovine serum albumin in poly(lactide-co-glycolide) microspheres by the solid-in-oil-in-water technique. J. Pharm. Pharmacol., London, v. 53, p. 167-178, 2001.
21. CHANDY, T.; MOORADIAN, D. L.; RAO, G. H. Chitosan/polyethylene glycol-alginate microcapsules for oral delivery of hirudin. J. App. Polym. Sci., Washington, v. 70, p. 2143-2153, 1998.
22. CHEN, T. Formulation concerns ofprotein drugs. Drug Dev. Ind. Pharm., New York, v. 18, p. 1311-1354, 1992.
23. CHO, N. H.; SEONG, S. Y.; CHUN, K. H.; KIM, Y. H.; KWON, I. C.; AHN, B. Y.; JEONG, S. Y. Novel mucosal immunization with polysaccharide-protein conjugates entrapped in alginate microspheres. J. Control Release, Amsterdam, v. 53, p. 215-224, 1998.
24. CONWAY, B. R.; ALPAR, H. O. Double emulsion microencapsulation of proteins as model antigens using polylactide polymers: effect of emulsifier on the microsphere characteristics and release kinetics. Eur. J. Pharm. BioPharm., Stuttgart, v. 42, p. 42-48, 1996.
25. COPPI, G.; IANNUCCELLI, V.; LEO, E.; BERNABEI, M. T.; CAMERONI, R. Chitosan-alginate microparticles as a protein carrier. Drug Dev. Ind. Pharm. New York, v. 27, p. 393-400, 2001.
26. COUVREUR, P.; DUBERNET, C.; PUISIEUX, F. Controlled drug delivery with nanoparticles: current possibilities and future trends. Eur. J. Pharm. BioPharm., Stuttgart, v. 41, p. 2-13, 1995.
27. CROTTS, G.; PARK, T. G. Preparation of porous and nonporous biodegradable polymeric hollow microspheres. J. Controlled Release, Amsterdam, v. 35, p. 91-105, 1995.
28. DAMGE, C.; MICHEL, C.; APRAHAMIAN, M.; COUVREUR, P.; DEVISSAGUET, J. P. Nanocapsules as carriers for oral peptide delivery. J. Controlled Release, Amsterdam, v. 13, p. 233-239, 1990.
29. DAMGE, C.; VONDERSCHER, J.; MARBACH, P.; PINGET, M. Polyalkyl cyanoacrylate nanocapsules as a delivery system in the rat for octreotide, a long-acting somatostatin analog. J. Pharm. Pharmacol., London, v. 49, p. 949-954, 1997a.
30. DAMGE, C.; VRANCKX, H.; BALSCHMIDT, P.; COUVREUR, P. Poly(alkyl cyanoacrylate) nanospheres for oral administration of insulin. J. Pharm. Sci., Washington, v. 86, p. 1403-1409, 1997b.
31. DONBROW, M. Introduction and overview. In: DONBROW, M., ed. Microcapsules and nanoparticles in medicine and Pharmacy. Boca Raton: CRC Press, 1992. p. 1-14.
32. EYLES, J. E.; ALPAR, H. O.; CONWAY, B. R.; KESWICK, M. Oral delivery and fate of poly(lactic acid) microsphere-encapsulated interferon in rats. J. Pharm. Pharmacol., London, v. 49, p. 669-674, 1997.
33. FIX, J. A. Strategies for delivery of peptides utilizing absorption-enhancing agents. J. Pharm. Sci., Washington, v. 85, p. 1282-1285, 1996.
34. GEARY, R. S.; SCHLAMEUS, H. W. Vancomycin and insulin used as models for oral delivery of peptides. J. Controlled Release, Amsterdam, v. 23, p. 65-74, 1993.
35. GIUNCHEDI, P.; CONTE, U. Spray-drying as a preparation method of microparticulate drug delivery systems: overview. STP Pharma. Sci., Paris, v. 5, p. 276-290, 1995.
36. GOMBOTZ, W. R.; WEE, S. F. Protein release from alginate matrices. Adv. Drug Deliv. Rev., Amsterdam, v. 31, p. 267-285, 1998.
37. HARI, P. R.; SHARMA, C. P. Comments on 'Modulation of protein release from chitosan-alginate microcapsules using the pH-sensitive polymer hydroxypropyl methyl cellulose acetate succinate'. J. Microencapsul., London, v. 15, p. 525-526, 1998.
38. HERRMANN, J.; BODMEIER, R. Effect of particle microstructure on the somatostatin release from poly(lactide) microspheres prepared by a W/O/W solvent evaporation method. J. Controlled Release, Amsterdam, v. 36, p. 63-71, 1995.
39. HILLERY, A. M.; TOTH, I.; FLORENCE, A. T. Copolymerised peptide particles. II: Oral uptake of a novel co-polymeric nanoparticulate delivery system for peptides. J. Controlled Release, Amsterdam, v. 42, p. 65-73, 1996.
40. HILLERY, A. M.; TOTH, I.; SHAW, A. J.; FLORENCE, A. T. Copolymerized peptide particles (CPP). Part 1. Synthesis, characterization and in vitro studies on a novel oral nanoparticulate delivery system. J. Controlled Release, Amsterdam, v. 41, p. 271-281, 1996.
41. HINCAL, A. A.; KAS, H. S. Microencapsulation technology: interfacial polymerization method. In: WISE, D. L., ed. Handbook of Pharmaceutical controlled release technology. New York: Marcel Dekker, 2000. p. 271-285.
42. HIROSUE, S.; MULLER, B. G.; MULLIGAN, R. C.; LANGER, R. Plasmid DNA encapsulation and release from solvent diffusion nanospheres. J. Controlled Release, Amsterdam, v. 70, p. 231-242, 2001.
43. HOSNY, E. A.; KHAN GHILZAI, N. M.; AL NAJAR, T. A.; ELMAZAR, M. M. Hypoglycemic effect of oral insulin in diabetic rabbits using pH-dependent coated capsules containing sodium salicylate without and with sodium cholate. Drug Dev. Ind. Pharm., New York, v. 24, p. 307-311, 1998.
44. ICHIKAWA, H.; FUKUMORI, Y. New applications of acrylic polymers for thermosensitive drug release. STP Pharma Sci., Paris, v. 7, p. 529-545, 1997.
45. JAIN, R. A. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials, Amsterdam, v. 21, p. 2475-2490, 2000.
46. JUNG, T.; KAMM, W.; BREITENBACH, A.; KAISERLING, E.; XIAO, J. X.; KISSEL, T. Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake? Eur. J. Pharm. BioPharm., Stuttgart, v. 50, p. 147-160, 2000.
47. KAS, H. S.; ONER, L. Microencapsulation using coacervation / phase separation: an overview of the technique and applications. In: WISE, D. L., ed. Handbook of Pharmaceutical controlled release technology. New York: Marcel-Dekker, 2000. p. 301-328.
48. KAWASHIMA, Y.; YAMAMOTO, A.; TAKEUCHI, H.; HINO, T.; NIWA, T. Properties of a peptide containing DL-lactide/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods. Eur. J. Pharm. BioPharm., Stuttgart, v. 45, p. 41-48, 1998.
49. KAWASHIMA, Y.; YAMAMOTO, H.; TAKEUCHI, H., KUNO, Y. Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm. Dev. Technol, New York, v. 5, p. 77-85, 2000.
50. KIDCHOB, T.; KIMURA, S.; IMANISHI, Y. Preparation, structure and release profile of polypeptide microcapsules. J. Controlled Release, Amsterdam, v. 40, p. 285-291, 1996.
51. KIM, C. K.; LEE, E.-J. The controlled release of blue dextran from alginate beads. Int. J. Pharm., Amsterdam, v. 79, p. 11-19, 1992.
52. KIM, J. C.; SONG, M. E.; LEE, E.-J.; PARK, S. K.; RANG, M. J.; AHN, H. J. Preparation of microspheres by an emulsification-complexation method. J. Colloid Interface Sci., Amsterdam, v. 248, p. 1-4, 20021.
53. KIMURA, T.; SATO, K.; SUGIMOTO, K.; TAO, R.; MURAKAMI, T.; KUROSAKI, Y.; NAKAYAMA, T. Oral administration of insulin as poly(vinyl alcohol)-gel spheres in diabetic rats. Biol. Pharm. Bull, Tokyo, v. 19, p. 897-900, 1996.
54. KREUTER, J. Nanoparticles. In: SWARBRICK, J.; BOYLAN, J. C., eds. Encyclopedia of Pharmaceutical technology, v. 10. New York: Marcel Dekker, 1994. p. 165-190.
55. LARIONOVA, N. V.; PONCHEL, G.; DUCHENE, D.; LARIONOVA, N. I. Biodegradable cross-linked starch/protein microcapsules containing proteinase inhibitor for oral protein administration. Int. J. Pharm., Amsterdam, v. 189, p. 171-178, 1999.
56. LEHR, C.-M. Lectin-mediated drug delivery: the second generation of bioadhesives. J. Controlled Release, Amsterdam, v. 65, p. 19-29, 2000.
57. LEHR, C.-M.; BOUWSTRA, J. A.; KOK, W.; DE BOER, A. G.; TUKKER, J. J.; VERHOEF, J. C.; BREIMER, D. D.; JUNGINGER, H. E. Effects of the mucoadhesive polymer polycarbophil on the intestinal absorption of a peptide drug in the rat. J. Pharm. Pharmacol., London, v. 44, p. 402-407, 1992.
58. LEMOINE, D.; WAUTERS, F.; BOUCHEND' HOMME, S.; PREAT, V. Preparation and characterization of alginate microspheres containing a model antigen. Int. J. Pharm., Amsterdam, v. 176, p. 9-19, 1998.
59. LIM, F.; SUN, A. M. Microencapsulation islets as bioartificial endocrine pancreas. Science, Washington, v. 210, p. 908-910, 1980.
60. LIM, L. Y.; WAN, L. S.; THAI, P. Y. Chitosan microspheres prepared by emulsification and ionotropic gelation. Drug Dev. Ind. Pharm., New York, v. 23, p. 981-985, 1997.
61. LOWE, P. J.; TEMPLE, C. S. Calcitonin and insulin in isobutylcyanoacrylate nanocapsules: protection against proteases and effect on intestinal absorption in rats. J. Pharm. Pharmacol., London, v. 46, p. 547-552, 1994.
62. LOWMAN, A. M.; MORISHITA, M.; KAJITA, M.; NAGAI, T.; PEPPAS, N. A. Oral delivery of insulin using pH responsive complexation gels. J. Pharm. Sci., Washington, v. 88, p. 933-937, 1999.
63. LUEBEN, H. L.; RENTEL, C.-O.; KOTZE, A. F.; LEHR, C.-M.; DE BOER, A. G.; VERHOEF, J. C.; JUNGINGER, H. E. Mucoadhesive polymers in peroral peptide drug delivery. IV. Polycarbophil and chitosan are potent enhancers of peptide transport across intestinal mucosae in vitro. J. Controlled Release, Amsterdam, v. 45, p. 15-23, 1997.
64. LUZZI, L. A. Microencapsulation. J. Pharm. Sci., Washington, v. 59, p. 1367-1376, 1970.
65. MA, X. Y.; PAN, G. M.; LU, Z.; HU, J. S.; BEI, J. Z.; JIA, J. H.; WANG, S. G. Preliminary study of oral polylactide microcapsulated insulin in vitro and in vivo. Diabetes Obes. Metab., v. 2, p. 243-250, 2000.
66. MANNING, M. C.; PATEL, K.; BORCHARDT, R. T. Stability of protein pharmaceuticals. Pharm. Res., Stuttgart, v. 6, p. 903-918, 1989.
67. MATHIOWITZ, E.; JACOB, J. S.; JONG, Y. S.; CARINO, G. P.; CHICKERING, D. E.; CHATURVEDI, P.; SANTOS, C. A.; VIJAYARAGHAVAN, K.; MONTGOMERY, S.; BASSETT, M.; MORRELL, C. Biologically erodable microspheres as potential oral drug delivery systems. Nature, London, v. 386, p. 410-414, 1997.
68. MORISHITA, I.; MORISHITA, M.; TAKAYAMA, K.; MACHIDA, Y.; NAGAI, T. Hypoglycemic effect of novel oral microspheres of insulin with protease inhibitor in normal and diabetic rats. Int. J. Pharm., Amsterdam, v. 78, p. 9-16, 1992.
69. MORISHITA, I.; MORISHITA, M.; TAKAYAMA, K.; MACHIDA, Y.; NAGAI, T. Enteral insulin delivery by microspheres in 3 different formulations using Eudragit L-100 and S-100. Int. J. Pharm., Amsterdam, v. 91, p. 29-37, 1993.
70. 1 by the addition of polyacrylic acid within acid-treated beads. J. Controlled Release, Amsterdam, v. 30, p. 241-251, 1994.
71. MURATA, Y.; MAEDA, T.; MIYAMOTO, E.; KAWASHIMA, S. Preparation of chitosan-reinforced alginate gel beads - efects of chitosan on gel matrix erosion. Int. J. Pharm., Amsterdam, v. 96, p. 139-145, 1993.
72. NAKAMURA, M. et al. Potential efficacy of gelatin microspheres as a new adjuvant for oral vaccination. STP Pharma Sci., Paris, v. 8, p. 67-73, 1998.
73. O'DONNELL, P. B.; MCGINITY, J. W. Preparation of microspheres by the solvent evaporation technique. Adv. Drug Deliv Rev., Amsterdam, v. 28, p. 25-42, 1997.
74. OGAWA, Y.; YAMAMOTO, M.; OKADA, H.; YASHIKI, T.; SHIMAMOTO, T. A new technique to efficiently entrap leuprolide acetate onto microcapsules of polylactic acid or copoly(lactic/glycolic) acid. Chem. Pharm. Bull, Tokyo, v. 36, p. 1095-1103, 1988.
75. OKHAMAFE, A. O.; AMSDEN, B.; CHU, W.; GOOSEN, M. F. Modulation of protein release from chitosan-alginate microcapsules using the pH-sensitive polymer hydroxypropyl methylcellulose acetate succinate. J. Microencapsul., London, v. 13, p. 497-508, 1996.
76. OPPENHEIM, R. C.; STEWART, N. F.; GORDON, L.; PATE, H. M. Production and evaluation of orally administered insulin nanoparticles. Drug Dev. Ind. Pharm., New York, v. 8, p. 531-546, 1982.
77. PATIL, R. T.; SPEAKER, T. J. Water-based microsphere delivery system for proteins. J. Pharm. Sci., Washington, v. 89, p. 9-15, 2000.
78. PEPPAS, N. A.; BURES, P.; LEOBANDUNG, W.; ICHIKAWA, H. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. BioPharm., Stuttgart, v. 50, p. 27-46, 2000.
79. POLK, A.; AMSDEN, B.; DE YAO, K.; PENG, T.; GOOSEN, M. F. Controlled release of albumin from chitosan-alginate microcapsules. J. Pharm. Sci., Washington, v. 83, p. 178-185, 1994.
80. PONCELET, D.; LENCKI, R.; BEAULIEU, C.; HALLE, J. P.; NEUFELD, R. J.; FOURNIER, A. Poduction of alginate beads by emulsification/internal gelation. I. Methodology. Appl. Microbiol. Biotechnol., v. 38, p. 39-45, 1992.
81. PUTNEY, S. D.; BURKE, P. A. Improving protein therapeutics with sustained-release formulations. Nat. Biotechnol., New York, v. 16, p. 153-157, 1998.
82. QUINTANAR-GUERRERO, D.; ALLEMANN, E.; FESSI, H.; DOELKER, E. Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Dev. Ind. Pharm., New York, v. 24, p. 1113-1128, 1998.
83. RADWAN, M. A. Enhancement of absorption of insulin-loaded polyisobutylcyanoacrylate nanospheres by sodium cholate after oral and subcutaneous administration in diabetic rats. Drug Dev. Ind. Pharm., New York, v. 27, p. 981-989, 2001.
84. RAFATI, H.; COOMBES, A. G.; ADLER, J.; HOLLAND, J.; DAVIS, S. S. Protein-loaded poly(DL-lactide-coglycolide) microparticles for oral administration: formulation, structural and release characteristics. J. Controlled Release, Amsterdam, v. 43, p. 89-102, 1997.
85. RAMADAS, M.; PAUL, W.; DILEEP, K. J.; ANITHA, Y.; SHARMA, C. P. Lipoinsulin encapsulated alginatechitosan capsules: intestinal delivery in diabetic rats. J. Microencapsul., London, v. 17, p. 405-411, 2000.
86. RAMKINSSOON-GANORKAR, C.; LIU, F.; BAUDYS, M.; KIM, S. W. Modulating insulin-release profile from pH/ thermosensitive polymeric beads through polymer molecular weight. J. Controlled Release, Amsterdam, v. 59, p. 287-298, 1999.
87. REMUNAN-LOPEZ, C.; LORENZO-LAMOSA, M. L.; VILA-JATO, J. L.; ALONSO, M. J. Development of new chitosan-cellulose multicore microparticles for controlled drug delivery. Eur. J. Pharm. BioPharm., Stuttgart, v. 45, p. 49-56, 1998.
88. RIBEIRO, A. J.; NEUFELD, R. J.; ARNAUD, P.; CHAUMEIL, J. C. Microencapsulation of lipophilic drugs in chitosan-coated alginate microspheres. Int. J. Pharm., Amsterdam, v. 187, p. 115-123, 1999.
89. RUBINSTEIN, A. et al. Rationale for peptide drug delivery to the colon and the potential of polymeric carriers as effective tools. J. Controlled Release, Amsterdam, v. 46, p. 59-73, 1997.
90. SAH, H. Protein behavior at the water/methylene chloride interface. J. Pharm. Sci., Washington, v. 88, p. 1320-1325, 1999.
91. SILVA, C.; RIBEIRO, A.; FERREIRA, D.; VEIGA, F. Administração oral de peptídeos e proteínas: III. Aplicação à insulina. Rev. Bras. Cien. Farm., São Paulo, v. 39, n. 1, p. 21-40, 2003.
92. SILVA, C.; RIBEIRO, A.; FERREIRA, D.; VEIGA, F. Administração oral de peptídios e proteínas: I. Estratégias gerais para aumento da biodisponibilidade oral. Rev. Bras. Cienc. Farm, São Paulo, v. 38, p. 125-140, 2002b.
93. SAKUMA, S. et al. Oral peptide delivery using nanoparticles composed of novel graft copolymers having hydrophobic backbone and hydrophilic branches. Int. J. Pharm., Amsterdam, v. 149, p. 93-106, 1997.
94. SARCIAUX, J. M.; ACAR, L.; SADO, P. A. Using microemulsion formulations for oral drug delivery of therapeutic peptides. Int. J. Pharm., Amsterdam, v. 120, p. 127-136, 1995.
95. SCHUGENS, C.; LARUELLE, N.; NIHANT, R.; JEROME, P.; TEYSSIE, P.; AL., E. Effect of the emulsion stability on the morphology and porosity of semicrystalline poly L-lactide microparticles prepared by W/O/W double emulsion-evaporation. J. Controlled Release, Amsterdam, v. 32, p. 161-176, 1994.
96. SERRES, A.; BAUDYS, M.; KIM, S. W. Temperature and pH-sensitive polymers for human calcitonin delivery. Pharm. Res, Stuttgart, v. 13, p. 196-201, 1996.
97. SHAH, D.; SHEN, W. C. Transcellular delivery of an insulin-transferrin conjugate in enterocyte-like Caco-2 cells. J. Pharm. Sci., Washington, v. 85, p. 1306-1311, 1996.
98. SHU, X. Z.; ZHU, K. J. Chitosan/gelatin microspheres prepared by modified emulsification and ionotropic gelation. J. Microencapsul., London, v. 18, p. 237-245, 2001.
99. SOPPIMATH, K. S.; AMINABHAVI, T. M.; KULKARNI, A. R.; RUDZINSKI, W. E. Biodegradable polymeric nanoparticles as drug delivery devices. J. Control Release, Amsterdam, v. 70, p. 1-20, 2001.
100. SORIANO, I.; DELGADO, A.; DIAZ, R. V.; EVORA, C. Use of surfactant in polylactic acid protein microspheres. Drug Dev. Ind. Pharm., New York, v. 21, p. 549-558, 1995.
101. SRIAMORNSAK, P. Investigation of pectin as a carrier for oral delivery of proteins using calcium pectinate gel beads. Int. J. Pharm., Amsterdam, v. 169, p. 213-220, 1998.
102. SUZUKI, A.; MORISHITA, M.; KAJITA, M.; TAKAYAMA, K.; ISOWA, K.; CHIBA, Y.; TOKIWA, S.; NAGAI, T. Enhanced colonic and rectal absorption of insulin using a multiple emulsion containing eicosapentaenoic acid and docosahexaenoic acid. J. Pharm. Sci., Washington, v. 87, p. 1196-1202, 1998.
103. TAKAHATA, H.; LAVELLE, E. C.; COOMBES, A. G.; DAVIS, S. S. The distribution of protein asociated with poly(DL-lactide-co-glycolide) microparticles and its degradation in simulated body fluids. J. Controlled Release, Amsterdam, v. 50, p. 237-246, 1998.
104. TAKEUCHI, H.; YAMAMOTO, H.; KAWASHIMA, Y. Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv. Drug Deliv. Rev., Amsterdam, v. 47, p. 39-54, 2001.
105. TRENKTROG, T.; MULLER, B. W.; SEIFERT, J. In vitro-investigation into the enhancement of intestinal peptide absorption by emulsion systems. Eur. J. Pharm. BioPharm., Stuttgart, v. 41, p. 284-290, 1995.
106. UCHIDA, T.; YASUDA, N.; MATSUYAMA, K. Preparation and characterization of biodegradable or enteric-coated microspheres containing the protease inhibitor camostat. J. Pharm. Pharmacol., London, v. 53, p. 255-261, 2001.
107. VANDENBERG, G. W.; DROLET, C.; SCOTT, S. L.; DE LA NOUE, J. Factors affecting protein release from alginate-chitosan cocervate microcapsules during prodution and gastric/intestinal simulation. J. Controlled Release, Amsterdam, v. 77, p. 297-307, 2001.
108. WAN, L. S.; HENG, P. W.; CHAN, L. W. Drug encapsulation in alginate microspheres by emulsification. J. Microencapsul., London, v. 9, p. 309-316, 1992.
109. WEHRLE, P.; MAGENHEIM, B.; BENITA, S. Influence of process parameters on the PLA nanoparticle size distribution, evaluated by means of factorial design. Eur. J. Pharm. BioPharm., Stuttgart, v. 41, p. 19-26, 1995.
110. YOO, H. S.; CHOI, H. K.; PARK, T. G. Protein-fatty acid complex for enhanced loading and stability within biodegradable nanoparticles. J. Pharm. Sci., Washington, v. 90, p. 194-201, 2001.