Biodegradable fumarate‐based drug‐delivery systems for ophthalmic applications

Abstract

The function of a photocrosslinked poly(propylene fumarate) (PPF)/poly(N-vinyl pyrrolidone) (PVP) matrix for the sustained release of three ophthalmic model drugs, acetazolamide (AZ), dichlorphenamide (DP), and timolol maleate (TM), was investigated. The drugs differ in molecular weight and degree of dissociation in aqueous environments; both are parameters that significantly influence drug diffusivity. AZ, DP, and TM-loaded cylindrical rods (10 mm length, 0.6 mm diameter) were fabricated by photoinduced cross-copolymerization of PPF and N-vinyl pyrrolidone (NVP) in molds. The released amounts of AZ, DP, TM, and NVP were determined by high-performance liquid chromatography (HPLC). The effects of drug properties and loading on the release kinetics were investigated. The in vitro release of AZ, DP, and TM was well sustained from the polymer matrices over a period of approximately 210, 270, and 250 days, respectively. The release kinetics correlated with the HPLC retention profiles of the different drugs. Following a small initial burst release (<10%), a dual modality release controlled by diffusion and bulk erosion was found for all drugs. Drug release rates of up to 4 microg/day were reached. Matrix drug loading generally affected the extent of the burst release, release kinetics, as well as the matrix water content and matrix degradation that were determined gravimetrically. Microcomputed tomography was used to image structural and dimensional changes of the devices. A preliminary rabbit implantation study revealed promising ocular biocompatibility of drug-free PPF/PVP matrices. All results indicate the potential of photocrosslinked PPF-based matrices as polymeric carriers for long-term ophthalmic drug delivery.

An Anti‐angiogenic Reverse Thermal Gel as a Drug‐Delivery System for Age‐Related Wet Macular Degeneration

“…We also observed a small initial burst release for all the formulations. It is well-documented that burst release from injectable systems is higher than from pre-fabricated architectures such as implants; [28] thus we hypothesize that the observed burst release can be attributed to bevacizumab lost during the phase transition. Larger bursts were observed in the 15 wt% system, as well as with higher bevacizumab doses.…”

Subconjunctival Delivery of Dorzolamide-Loaded Poly(ether-anhydride) Microparticles Produces Sustained Lowering of Intraocular Pressure in Rabbits

“…32 An implant created from photo-cross-linked poly(propylene fumarate) (PPF)/poly( N -vinylpyrrolidone) (PVP) matrix released the CAI acetazolamide over a period of approximately 200 days. 33 Implant placement, however, requires that incisions are made in the conjunctiva and CAI releasing implants were associated with inflammation and fibrosis. Here we describe an additional formulation for controlled release of CAIs that allows sustained IOP lowering after minimal conjunctival manipulation on particle injection.…”

Novel poly-DL-lactide-polycaprolactone copolymer based flexible drug delivery system for sustained release of ciprofloxacin

“…Other polymers like cross-linked PVP have also shown a biphasic release profile owing to the initial burst and then release occurring due to the combined effect of erosion and diffusion (Hacker et al, 2009).…”