Monitoring Microviscosity and Microacidity of the Albumin Microenvironment Inside Degrading Microparticles from Poly(lactide-co-glycolide) (PLG) or ABA-triblock Polymers Containing Hydrophobic Poly(lactide-co-glycolide) A Blocks and Hydrophilic Poly(ethyleneoxide) B Blocks

Pharmaceutical Research - Tập 15 Số 5 - Trang 787-793 - 1998
Mäder, Karsten1, Bittner, Beate1, Li, Youxin1, Wohlauf, Wilko2, Kissel, Thomas1
1Department of Pharmaceutics and Biopharmacy, Philipps-University Marburg, Germany
2Institute of Pharmacy, Humboldt-University Berlin, Berlin, Germany

Tóm tắt

Purpose. The purpose of this study was to monitor the microenvironment of an encapsulated model protein during the release from biodegradable microparticles (MP) made from three different polymers, namely poly(lactide-co-glycolide) (PLG) and ABA-triblock polymers containing hydrophobic poly(lactide-co-glycolide) A blocks and hydrophilic poly(ethyleneoxide) B blocks with an A:B ratio of 90:10 (ABA10) and 70:30 (ABA30). Methods. MP loaded with spin labeled albumin were prepared by a w/o/w technique. The particles were characterized by light scattering and electron microscopy. In vitro release of albumin was determined by size exclusion chromatography. Light microscopic experiments were conducted to visualize water penetration in the matrix. The protein microenvironment inside the degrading microparticles was characterized noninvasively by 2 GHz EPR spectroscopy. Results. Water penetrated rapidly into all MP in the range of few minutes. A burst release was observed for PLG. The release from ABA block-polymers continued for over 14 days despite the rapid solubilization of the protein inside the microparticles. The initial microviscosity of the protein environment inside the ABA particles after exposure to buffer was 2 mm2/s and increased with time. A gradual decrease of the pH to a value of 3.5 was observed within the MP. Conclusions. The data indicate that the microviscosity and microacidity inside protein loaded microparticles can be studied nondestructively by EPR spectroscopy. Our results clearly demonstrate that ABA-block polymers are superior to PLG allowing a controlled release of proteins from swollen microspheres.

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Tài liệu tham khảo

citation_title=Formulation and delivery of proteins and peptides; citation_publication_date=1994; citation_id=CR1; citation_publisher=ACS

citation_journal_title=CRC Crit. Rev. Therap. Drug carrier syst.; citation_title=Biodegradable microspheres in drug delivery; citation_author=H. Okada, H. Toguchi; citation_volume=12; citation_publication_date=1995; citation_pages=1-99; citation_id=CR2

citation_journal_title=Biomaterials; citation_title=Noninvasive in vivo characterization of release processes in biodegradable polymers by low frequency Electron Paramagnetic Resonance Spectroscopy; citation_author=K. Mäder, B. Gallez, K. J. Liu, H. M. Swartz; citation_volume=17; citation_publication_date=1996; citation_pages=459-463; citation_id=CR3

citation_journal_title=J. Contr. Rel.; citation_title=Synthesis and properties of biodegradable ABA triblock copolymers consisting of poly(L(+)lactide acid), or poly(L(+)lactide acid-co-glycolic acid) A-blocks attached to central polyoxyethylene B-blocks; citation_author=Y. Li, T. Kissel; citation_volume=27; citation_publication_date=1993; citation_pages=247-257; citation_id=CR4

B. Bittner, K. Mäder, Y. X. Li, and T. Kissel. Evaluation of the microenvironment inside biodegradable microspheres from ABA triblock copolymers of poly(1-lactide-co-glycolide) and poly(ethyleneoxide) prepared by spray drying. Proc. 24 Int. Symp. Control. Rel. Bioact. Mater. (1997).

citation_journal_title=J. Contr. Rel.; citation_title=In-vitro degradation and bovine serum albumin release of the ABA triblock copolymers consisiting of poly(L(+)lactide acid), or poly(L(+)lactide acid-co-glycolic acid) A-blocks attached to central polyoxyethylene B-blocks; citation_author=Y. Li, C. Volland, T. Kissel; citation_volume=32; citation_publication_date=1994; citation_pages=121-128; citation_id=CR6

citation_journal_title=J. Contr. Rel.; citation_title=Parenteral protein delivery systems using biodegradable polyesters of ABA block structure, containing hydrophobic poly(lactide-co-glycolide) A blocks and hydrophilic poly(ethyleneoxide) B blocks; citation_author=T. Kissel, Y. X. Li, C. Volland, S. Görich, R. Koneberg; citation_volume=39; citation_publication_date=1996; citation_pages=315-326; citation_id=CR7

M. Morlock, H. Koll, G. Winter and T. Kissel. Erythropoietin loaded microspheres prepared from biodegradable LPLG-PEO-LPLG triblock copolymers: protein stabilization and in-vitro release properties. J. Control. Release, accepted.

citation_journal_title=Pharmazie; citation_title=The application of EPR spectroscopy in the field of pharmacy; citation_author=K. Mäder, H. M. Swartz, R. Stösser, H.-H. Borchert; citation_volume=49; citation_publication_date=1994; citation_pages=97-101; citation_id=CR9

citation_journal_title=J. Pharm. Sci.; citation_title=Noninvasive in vivo monitoring of drug release and polymer erosion from biodegradable polymers by EPR spectroscopy and NMR imaging; citation_author=K. Mäder, G. Bacic, A. Domb, O. Elmalak, R. Langer, H. M. Swartz; citation_volume=86; citation_publication_date=1997; citation_pages=126-134; citation_id=CR10

citation_journal_title=Pharm. Res.; citation_title= In vitro I in vivo comparison of drug release and polymer erosion from biodegradable P(FAD-SA) polyanhydrides—a noninvasive approach by the combined use of Electron Paramagnetic Resonance Spectroscopy and Nuclear Magnetic Resonance Imaging; citation_author=K. Mäder, Y. Cremmilleux, A. Domb, J. F. Dunn, H. M. Swartz; citation_volume=14; citation_publication_date=1997; citation_pages=820-826; citation_id=CR11

citation_title=Proton exchange in stable nitroxide radicals: pH-sensitive spin probes; citation_inbook_title=Imidazoline nitroxides; citation_publication_date=1988; citation_pages=37-80; citation_id=CR12; citation_author=V. V. Khramtsov; citation_author=L. M. Weiner; citation_publisher=CRC press

citation_journal_title=Polymer; citation_title=Nondestructive and localised assessment of acidic microenvironments inside biodegradable polyanhydrides by spectral spatial Electron Paramagnetic Resonance Imaging (EPRI); citation_author=K. Mäder, S. Nitschke, R. Stösser, H.-H. Borchert, A. Domb; citation_volume=38; citation_publication_date=1997; citation_pages=4785-4794; citation_id=CR13

citation_journal_title=Biochimica et Biophysica Acta; citation_title=The application of pH-sensitive spin labels to studies of surface potential and polarity of phopholipid membrane and proteins; citation_author=V. V. Khramtsov, D. Marsh, L. Weiner, V. A. Reznikov; citation_volume=1104; citation_publication_date=1992; citation_pages=317-324; citation_id=CR14

citation_journal_title=J. Biomat. Sci. Polym. Edn.; citation_title=Poly-DL-lactic acid: Polyethylene glycol block copolymers. The influence of polyethylene glycol on the degradation of poly-DL-lactic acid; citation_author=S. S. Shah, K. J. Zhu, C. G. Pitt; citation_volume=5; citation_publication_date=1994; citation_pages=421-431; citation_id=CR15

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Pharmaceutical Research

Tập 15 Số 5

787-793

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