Poly(hexyl‐substituted lactides): Novel injectable hydrophobic drug delivery systems

Abstract

Poly(hexyl-substituted lactides) (PHLA) as new hydrophobic polyesters with controlled molecular weights and narrow distributions were synthesized by ring-opening polymerization (ROP) using tin(II) 2-ethylhexanoate (Sn(Oct) 2 ) and benzyl alcohol as catalyst and initiator. Glass transition temperatures (T g ) and zero shear viscosities (g 0 ) at 258C could be modulated from T g ¼ À428C to À108C and 40 to 4850 Pa s, respectively, by varying the polymer molecular weight and the number of hexyl groups along the polymer chain. Degradation studies were performed in terms of both mass and molecular weight loss in the course of time. The degradation mechanism is shown to be of the ''bulk erosion'' type, and comparable to standard poly(D,L-lactide) (PLA). Despite the increased steric hindrance in the poly(monohexyl-substituted lactide) (PmHLA) due to the hexyl side groups, its degradation rate at pH 7.4 and 378C was found to be slightly higher than observed for the analogue standard PLA. This could be attributed to the flexible rubbery state of the hexyl-substituted polymer (T g *À158C) at the physiological temperature, which is favoring the degradation in comparison to the rigid and glassy standard PLA (T g *408C). In contrast, degradation studies performed at 608C, where both polymers are above their glass transition temperature, confirmed that the degradation rate is lower for the sterically more hindered PmHLA. The degradation products were analyzed by ESI-MS. Hydrolysis lead first to the corresponding oligo-ester fragments and finally to the nontoxic 2-hydroxyoctanoic acid and lactic acid. Tetracycline was tested as a model drug for release studies. This drug was found to be released faster and in higher amounts in its active form from the PHLA matrix than from standard PLA. The results presented in this work demonstrate the potential of these hydrophobic polylactide-based semisolid materials as an alternative to conventional PLA/PLGA for injectable drug delivery systems. 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A: [55][56][57][58][59][60][61][62][63][64][65] 2007

Glass Transitions in Polylactides

“…Investigation of poly(n-hexylglycolide) as an injectable drug delivery system suggests that polylactides with low T g s may have some importance for biomedical applications. 62 The data obtained from n-alkyl substituted polyglycolides suggest that branched chains would more effectively increase T g . Although several polyglycolides with branched alkyl chains have been synthesized, the structural diversity is still modest.…”

Low Viscosity Poly(trimethylene carbonate) for Localized Drug Delivery: Rheological Properties and in vivo Degradation

“…For this purpose, injectable, fluid polymers that either gel in situ or possess high viscosity are being investigated as alternative approaches to the use of more conventional formulations such as microspheres, emulsions, and liposomes. [1][2][3][4][5][6][7][8][9][10] This interest is a result of advantages that include a relatively facile formulation approach coupled with retention at the injection site.…”

Emerging Technologies to Increase the Bioavailability of Poorly Water-Soluble Drugs

“…Much like copolymers prepared from amino acid-based block copolymers, ester-based copolymers can be derivatized to modulate drug-release rates or to increase drug loadings. The modifi cation of PLA to form poly(mono hexyl-substituted lactide) (PmHLA) was recently reported (Trimaille et al 2007 ) . The resulting hydrophobic PmHLA block exhibited glass transition temperatures signifi cantly lower than that of PLA and subsequently exhibited faster release rates of tetracycline.…”