Matrix modifications modulate ophthalmic drug delivery from photo-cross-linked poly(propylene fumarate)-based networks.
In this work, different modifications of photo-cross-linked poly(propylene fumarate)/poly(N-vinyl pyrrolidone) (PPF/PNVP) matrices were studied for their effect on the release kinetics of two ophthalmic drugs. The hydrophilicity of solid PPF/PNVP matrices loaded with acetazolamide (AZ) or timolol maleate (TM) was increased by adding various amounts of poly(ethylene glycol) (PEG) or by increasing the amount of N-vinyl pyrrolidone (NVP) in the polymer mixture prior to cross-linking. The in vitro release studies that utilized high-performance liquid chromatography for quantification revealed highly accelerated drug release from the matrices with increasing contents of the hydrophilic modifier. AZ was released from matrices containing 5% PEG in 56 days, which equals approximately 25% of the release period found for the unmodified matrices. A comparable acceleration in drug release was found for TM-loaded samples modified with 5% PEG. These studies further revealed that 1% PEG is sufficient to shorten the TM release duration by one-third. A significant acceleration in drug release was also found for the samples that were fabricated from a PPF-NVP mixture with increased NVP content. Matrix water content and erosion were assessed gravimetrically. Micro-computed tomography was used to image structural changes of the release systems and shed light on the drug-release mechanism. This study showed that hydrophilic matrix modifications of PPF/PNVP matrices accelerate the drug release of two ophthalmic drugs and represent a suitable tool to adjust drug-release rates from PPF-based matrices for different therapeutic needs.
Haesslein
A
A
Department of Bioengineering, Rice University, P.O. Box 1892, Houston, TX 77251-1892, USA.
Hacker
M C
MC
Ueda
H
H
Ammon
D M
DM
Borazjani
R N
RN
Kunzler
J F
JF
Salamone
J C
JC
Mikos
A G
AG
D000086:Acetazolamide / Q000737:chemistry / Q000378:metabolism; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism; D004232:Diuretics / Q000737:chemistry / Q000378:metabolism; D004333:Drug Administration Routes; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005123:Eye / Q000737:chemistry / Q000378:metabolism; D005650:Fumarates / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D009883:Ophthalmic Solutions / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011126:Polypropylenes / Q000138:chemical synthesis / Q000737:chemistry*; D013999:Timolol / Q000737:chemistry / Q000378:metabolism
D000959:Antihypertensive Agents; D004232:Diuretics; D004337:Drug Carriers; D005650:Fumarates; D009883:Ophthalmic Solutions; D011108:Polymers; D011126:Polypropylenes; C097850:poly(propylene fumarate); D011092:Polyethylene Glycols; D013999:Timolol; D000086:Acetazolamide