Lauric Acid Derived Polyanhydrides: Synthesis, Characterization, In vitro Degradation, and Drug Release Behavior
Kevin B. Dagbay1 and Florentino C. Sumera*
1Natural Sciences Research Institute,
University of the Philippines, Diliman, Quezon City
*Institute of Chemistry, University of the Philippines,
Diliman, Quezon City 1101
corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
The fatty acid derived polyanhydrides were synthesized from hydroxylauric acid maleate and sebacic acid (SA). Hydroxylauric acid maleate (HOLAM) diacid half-ester was prepared from the reaction of hydroxy lauric acid with maleic anhydride. Copolymers of HOLAM and SA were synthesized by melt polycondensation to yield polymers with molecular weights of 47,000 to 240,000 g/mol and with yields of 55 to 75%. Structural characteristics of the monomers and polyanhydrides were characterized using FT-IR, 1H/13C-NMR, DSC, GPC, and SEM. Results showed that these polymers have low melting points (51-76° C) and are degradable under simulated in vitro physiological condition (phosphate buffer, pH 7.4 at 37° C). The extent of degradation and cyrstallinity of these polymers depend mainly on HOLAM content of the copolymers. Phase inversion technique produced poly(SA:HOLAM) microspheres, wherein, particle size (1.33-2.36 μm) and drug release rates were found dependent on the HOLAM weight ratio. Biphasic in vitro drug release profile was observed for ciprofloxacin-loaded poly(SA:HOLAM) microspheres. Kinetic study using models for drug release showed that release by diffusion rather than by erosion was followed.
INTRODUCTION
Polyanhydrides have been used since the 1980’s as polymeric drug delivery system (Rosen et al. 1983; Jain et al. 2005). For a particular application the rate of degradation of polyanhydrides can be manipulated by change in the monomer type and ratio without affecting their attribute of biodegradability. Thus, selection of monomers becomes crucial to obtain the polymer of desired degradability. A case in point are the fatty acids which are found good candidates for polymeric drug delivery system because they can moderate the rate of drug release in biodegradable polymers such as polyanhydrides due to their hydrophobicity (Maniar et al. 1994; Teomin & Domb 2001; Shikanov et al. 2005). . . . . . . . . . .
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