A bioresorbable, polylactide reservoir for diffusional and osmotically controlled drug delivery

Abstract

The purpose of this study was to design and characterize a zero-order bioresorbable reservoir delivery system (BRDS) for diffusional or osmotically controlled delivery of model drugs including macromolecules. The BRDS was manufactured by casting hollow cylindrical poly (lactic acid) (PLA): polyethylene glycol (PEG) membranes (10 x 1.6 mm) on a stainless steel mold. Physical properties of the PLA:PEG membranes were characterized by solid-state thermal analysis. After filling with drug (5 fluorouracil [5FU] or fluorescein isothiocyanate [FITC]-dextran:mannitol, 5:95 wt/wt mixture) and sealing with viscous PLA solution, cumulative in vitro dissolution studies were performed and drug release monitored by ultraviolet (UV) or florescence spectroscopy. Statistical analysis was performed using Minitab ® (Version 12). Differential scanning calorimetry thermograms of PLA:PEG membranes dried at 25°C lacked the crystallization exotherms, dual endothermal melting peaks, and endothermal glass transition observed in PLA membranes dried at -25°C. In vitro release studies demonstrated zero-order release of 5FU for up to 6 weeks from BRDS manufactured with 50% wt/wt PEG (drying temperature, 25°C). The release of FITC dextrans of molecular weights 4400, 42 000, 148 000, and 464 000 followed zero-order kinetics that were independent of the dextran molecular weight. When monitored under different concentrations of urea in the dissolution medium, the release rate of FITC dextran 42 000 showed a linear correlation with the calculated osmotic gradient(∆π ). PEG inclusion at 25°C enables manufacture of uniform, cylindrical PLA membranes of controlled permeability. The absence of molecular weight effects and a linear dependence of FITCdextran release rate on∆π confirm that the BRDS can be modified to release model macromolecules by an osmotically controlled mechanism.

Effect of thickness and PEG addition on the hydrolytic degradation of PLLA

“…Cylindrical, hollow, PLLA and PLLA : PEG films were manufactured as described previously [13]. Briefly, a stainless steel mold with 1.6-mm rods was dipped into a 10% (w/w) polymeric solution of varying PLLA : PEG ratios (100 : 0, 85 : 15 or 70 : 30, w/w) in dichloromethane.…”

“…We recently reported the design of a cylindrical, biodegradable polylactide reservoir for zero-order delivery of model macromolecular drugs [13]. PLLA is a hydrophobic, semi-crystalline polymer that is impermeable to water.…”

PLGA-Based Nanoparticles as Cancer Drug Delivery Systems

“…However, numerous processes or events influence the rate of drug diffusion and the degradation kinetics, for example dissolution of the drug (in combination with diffusion) (Wong et al, 2001), Diffusion through waterfilled pores (Kim et al, 2006), Diffusion through the polymer matrix (Sun et al, 2008), Hydrolysis (Bishara and Domb, 2005), Erosion (Shah et al, 1992), Osmotic pumping (Jonnalagadda and Robinson, 2000), Water absorption/Swelling (Mochizuki et al, 2008), Polymerdrug interactions (Manuela Gaspar et al, 1998), Drug-drug interactions (Zhu and Schwendeman, 2000), Polymer relaxation (Gagliardi et al, 2010), Pore closure (Kang and Schwendeman, 2007), Heterogeneous degradation (Park, 1995), Formation of cracks or deformation (Matsumoto et al, 2006) and Collapse of the polymer structure (Friess and Schlapp, 2002;Fredenberg et al, 2011). Controlled drug release from PLGA-based DDSs is complex, and many processes that influence drug release affect each other in many ways.…”

Formulation, Characterization, and In Vitro Evaluation of Bioadhesive Gels Containing 5-Fluorouracil

“…The resulting solutions were then filtered through 0.45-μm membrane filters and subjected to UV spectrophotometric analysis at 267 nm. [30] pH Measurements…”