Search

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 (eta(0)) at 25 degrees C could be modulated from T(g)= -42 degrees C to -10 degrees C 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 37 degrees C 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) approximately -15 degrees C) at the physiological temperature, which is favoring the degradation in comparison to the rigid and glassy standard PLA (T(g) approximately 40 degrees C). In contrast, degradation studies performed at 60 degrees C, 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.

Biodegradable nerve guidance channels (NGCs) represent a promising alternative to current clinical nerve repair procedures. To be suitable as a NGC material, the polymer system should possess elastomeric properties and degrade at a defined rate without interfering with the regenerating environment. Polymers made of non-crystallizable blocks of poly[glycolide-co-(epsilon-caprolactone)]-diol and crystallizable blocks of poly[(R)-3-hydroxybutyric acid-co-(R)-3-hydroxyvaleric acid]-diol (PHB) can be modulated so as to respond to those criteria. Tubular structures were fabricated from three different types of materials containing either 41, 17 or 8 wt% PHB. Nerve regeneration through a 10 mm long NGC using a transected sciatic nerve model with an 8 mm gap was studied in rats at 4, 12 and 24 weeks. Out of 26 implanted NGCs, 23 contained regenerated tissue cables centrally located within the channel lumen and composed of numerous myelinated axons and Schwann cells. No significant difference in the degree of regeneration was observed between the various channel types. The inflammatory reaction associated with the polymer degradation had not interfered with the nerve regeneration process. Macrophages and giant cells surrounded polymer material remnants. A weight loss of 33, 74 and 88% for polymers containing 41, 17 and 8 wt% PHB was observed after 24 weeks by nuclear magnetic resonance (NMR) anaylsis, respectively. In all cases, the polymer fragments had a porous appearance with multiple surface cracks as evidenced by scanning electron microscopical analysis. Guidance channels made of 8 wt% PHB containing polymer displayed the highest degree of degradation at 24 weeks with only small polymer fragments remaining. The present study suggests that this new biodegradable elastomeric polymeric material holds promises for its utilization as nerve guidance channels.

Poly(ortho esters) are currently under investigation as a carrier system for an antiproliferative agent in glaucoma filtering surgery. The present investigation illustrates the development of a series of self-catalyzed poly(ortho ester). These polymers contain short dimer segments of alpha-hydroxy acids in their backbone and are prepared by the addition of different polyols to the diketene acetal 3,9-diethylidene-2,4,8,10-tetra-oxaspiro-[5.5]-undecane. The structures were confirmed by NMR- and FT-IR-spectroscopy. The polymers were characterized by determination of the molecular weight, the glass transition temperature and the rheological behavior. The amount of residual solvents was also analyzed. The characteristics of the polymer can be varied by the type of polyol incorporated in its backbone. Since poly(ortho ester) is susceptible to acid-catalyzed degradation, the polymer hydrolysis can be controlled by the amount of incorporated portion of alpha-hydroxy acid. Due to the high hydrophobicity of the polymer structure, the ester bonds are more susceptible to hydrolysis than the ortho ester bonds in the polymer backbone. The hydrolysis proceeds via initial protonation of the exocyclic alkoxy group to yield pentaerythritol dipropionate and the free diol. In a next step, the pentaerythritol dipropionate hydrolysis to pentaerythritol and propionic acid. The molecular weight decrease, weight loss and the pH profile of the polymer in aqueous medium were monitored during the degradation.