Absorbable biopolymers derived from dimer fatty acids

Wiley - Tập 31 Số 5 - Trang 1275-1285 - 1993
Abraham J. Domb1, Manoj Maniar2
1The Hebrew University of Jerusalem, School of Pharmacy, Faculty of Medicine, Department of Pharmaceutical Chemistry, Jerusalem, Israel 91120
2Nova Pharmaceutical Corporation, Drug Delivery Laboratories, 6200 Freeport Center, Baltimore, Maryland 21224

Tóm tắt

Abstract

A new class of aliphatic copolyanhydrides was synthesized from nonlinear hydrophobic dimers (FAD) of erucic acid and sebacic acid which possessed the desired physico‐chemical and mechanical properties for use as a carrier for drugs. The polymers were synthesized by melt condensation to yield film‐forming polymers with molecular weights of 250,000. The copolymer composition was determined by 1H‐NMR and gravimetric methods. In vitro degradation studies showed that these polymers degrade following a first‐order kinetics with a rapid degradation in the first 10 days leaving a residue which is mostly the FAD comonomer. The drug release from the polymer also followed a first‐order kinetics which correlates with the degradation process of the polymer. Drugs like carboplatin, methotrexate, tetracycline, and gentamicin were released in vitro for over 2 weeks and in some cases over 6 weeks. In vivo biocompatibility tests in rats and rabbits in the brain, muscle, and subcutaneously, demonstrated their toxicological inertness and biodegradability. The 1 : 1 copolymer of FAD : SA was selected as a carrier for various applications including a gentamicin‐releasing implant which is now undergoing human clinical trials for the treatment of osteomyelitis. © 1993 John Wiley & Sons, Inc.

Từ khóa


Tài liệu tham khảo

A. J.Domb S.Amselem andM.Maniar inPolymeric Biomaterials S. Dumitriu Ed. Dekker New York in press.

A. J.Domb S.Amselem andM.Maniar Polym. Adv. Technol. in press.

Domb A. J., Biopolymers

10.1002/jbm.820190806

10.1002/pola.1987.080251217

Maniar M., 1992, Proc. Int. Symp. Control. Rel. Bioact. Mater., 19, 317

10.1055/s-2007-1020331

M. Rock M. Green C. Fait M. Maniar A. J. Domb 1991 ACS Meeting Philadelphia PA

Bogdansky S., 1991, Proc. Int. Symp. Control. Rel. Bioact. Mater., 18, 319

10.1016/0168-3659(92)90087-8

A. J.DombandM.Maniar Second Jerusalem Conference on Pharm. Sci. and Clinical Pharm. Jerusalem May 1992.

Hannibal D., 1991, Proc. Int. Symp. Control. Rel. Bioact. Mater., 18, 672

A.Domb A.Olivi K.Judy M. L.Pinn M. G.Ewend J. H.Goodman andH.Brem ACS Meeting Philadelphia PA June 1991.

K. D.Judy A.Olivi A. J.Domb O. M.Colvin H.Brem Congress of Neurological Surgeons Orlando FL October1991.

L.Orlaff M.Mayberg A. J.Domb M.Maniar M. G.Glenn andR. A.Esclamado AIChE Symp. Los Angeles CA 1991.

E. L.Hamilton‐Byrd A. J.Sokoloff A. J.Domb L.Terr andK. E.Byrd Polym. Adv. Tech. in press.