Sustained protein release formulation using biodegradable polymeric microspheres = 생분해성 고분자 미립구를 이용한 지속성 단백질 방출 제제화 연구

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For the sustained release formulation of recombinant human growth hormone (rhGH), dissociable rhGH aggregates were microencapsulated within poly(D,L-lactic-co-glycolic acid) [PLGA] microparticles. rhGH aggregates were first produced by adding a small volume of aqueous rhGH solution into a partially water miscible organic solvent phase (ethyl acetate) containing PLGA. These rhGH aggregates were then microencapsulated within PLGA polymer phase by extracting ethyl acetate into an aqueous phase pre-saturated with ethyl acetate. Release profiles of rhGH from these microparticles were greatly affected by changing the volume of incubation medium. The released rhGH species consisted of mostly monomeric form having a correct conformation. This study reveals that sustained rhGH release could be achieved by microencapsulating reversibly dissociable protein aggregates within biodegradable polymers. Recombinant human growth hormone was encapsulated, by a double emulsion solvent evaporation method, within two biodegradable microspheres having different monomer compositions. Semi-crystalline poly(l-lactic acid) (PLLA) and amorphous poly(D,L-lactic-coglycolic acid) (PLGA) were used for the encapsulation of rhGH. Protein release profiles from the two microspheres were comparatively evaluated with respect to their morphological difference. Both of the microspheres similarly exhibited rugged surface and porous internal structures, but their inner pore wall morphologies were quite different. The slowly degrading PLLA microspheres had many nano-scale reticulated pores on the wall, while the relatively fast degrading PLGA micropsheres had a non-porous and smooth wall structure. From the PLLA microspheres, rhGH was released out in a sustained manner with an initial - 20 % burst, followed by constant release, and almost 100 % complete release after a one month period. In contrast, the PLGA microspheres showed a similar burst level of 20 %, followed by much slower release, but incomple...
Advisors
Park, Tae-Gwanresearcher박태관researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2005
Identifier
244505/325007  / 020005094
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2005.2, [ x, 105 p. ]

Keywords

biodegradable; protein; microsphere; Sustained release; PLGA; 고분자; 생분해성; 단백질; 미립구; 지속방출

URI
http://hdl.handle.net/10203/27585
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=244505&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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