Nonlinear fatty acid terminated polyanhydrides.
A systemic study on the synthesis, characterization, degradation, drug release, and stability of nonlinear fatty acid terminated poly(sebacic anhydride) (PSA) is reported. Ricinoleic acid was transformed into a nonlinear fatty acid by esterification with fatty acid chlorides of C8-C18 chain length in the presence of pyridine. Pure nonlinear fatty acids were obtained by purification of the reaction product using column chromatography. Poly(sebacic acid)s terminated with 30 wt % of various nonlinear fatty acids were synthesized by melt condensation to yield waxy off-white materials with molecular weights in the range of 5000-9000. The terminated polymers are soluble in common organic solvents and melt at temperatures between 70 and 79 degrees C, which allow their fabrication into microspheres and implants. These polymers degrade into their counterparts during a period of a few weeks while constantly releasing an incorporated drug. The incorporation of nonlinear fatty acid terminals to poly(sebacic anhydride) increased the polymer hydrophobicity and decreased polymer crystallinity when compared to PSA or to linear fatty acid terminated PSA. The hydrophobic nonlinear side chains retard water from penetrating into the polymer mass, which resulted in higher stability and surface erosion front mechanism of polymer degradation and drug release.
Teomim
D
D
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Domb
A J
AJ
D000812:Anhydrides / Q000138:chemical synthesis* / Q000737:chemistry*; D002849:Chromatography, Gas; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D004355:Drug Stability; D005227:Fatty Acids / Q000737:chemistry*; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D008727:Methotrexate / Q000378:metabolism; D008863:Microspheres; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry*; D012277:Ricinoleic Acids / Q000737:chemistry; D012995:Solubility; D012997:Solvents; D013696:Temperature
D000812:Anhydrides; D004337:Drug Carriers; D005227:Fatty Acids; D011108:Polymers; D012277:Ricinoleic Acids; D012997:Solvents; C030521:ricinoleic acid; D008727:Methotrexate