Effect of thickness and PEG addition on the hydrolytic degradation of PLLA.
We previously demonstrated that cylindrical, biodegradable reservoirs fabricated with polylactide-polyethylene glycol (PLLA:PEG) films maintain constant permeability and enable zero-order drug delivery for up to 6 weeks in vitro. This research proposes that PEG not only enhances permeability but also extends of life of the device by allowing the escape of soluble degraded monomers thereby minimizing autocatalysis of PLLA. To test this hypothesis, cylindrical PLLA films with varying PEG concentrations (0-30%, w/w) and film-thickness (0.05-0.18 mm) were fabricated, and their degradation rate and thermal properties monitored for 23 weeks in vitro. The decrease in PLLA molecular weight for all films followed bi-exponential kinetics that fit the equation: y(t) = M(e(-K1t) + e(-K2t)), as was determined by a Pearson's coefficient > 0.95 for all films. The constant M was empirically determined to be equal to have the initial molecular weight of the degrading polymer. The value of K1 was 5-60 orders of magnitude greater than K2 and was attributed to the autocatalytic degradation based on its dependence on PEG concentration, film thickness, and correlation with the enthalpy change associated with the glass transition (deltaCp). K2 was attributed to simple hydrolytic cleavage of PLLA. The decrease in the value of K1 with PEG concentration and thickness, and the correlation of K1 with deltaCp, confirmed that the PLLA degradation can be controlled by incorporating PEG, as well as by modifying thickness.
Jonnalagadda
Sriramakamal
S
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, USIP, Philadelphia, PA 19104, USA.
Robinson
Dennis H
DH
D001672:Biocompatible Materials; D002384:Catalysis; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005898:Glass; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007773:Lactates / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors
D001672:Biocompatible Materials; D007773:Lactates; D011091:Polyesters; D011108:Polymers; C088513:poly(lactic acid-ethylene glycol); D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide)