Biodegradable fumarate-based drug-delivery systems for ophthalmic applications

M. C. Hacker, A. Haesslein, H. Ueda, W. J. Foster, C. A. Garcia, D. M. Amnion, R. N. Borazjani, J. F. Kunzler, J. C. Salamone, A. G. Mikos

Research output: Contribution to journalArticle

34 Scopus citations

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 ∼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 μg/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.

Original languageEnglish (US)
Pages (from-to)976-989
Number of pages14
JournalJournal of Biomedical Materials Research - Part A
Volume88
Issue number4
DOIs
StatePublished - Mar 15 2009

Keywords

  • Acetazolamide
  • Biodegradable polymer implant
  • Dichlorphenamide
  • Intraocular drug delivery
  • Poly(propylene fumarate)
  • Timolol maleate

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

Fingerprint Dive into the research topics of 'Biodegradable fumarate-based drug-delivery systems for ophthalmic applications'. Together they form a unique fingerprint.

Cite this