This work describes the application of UV light to trigger drug release from a biomaterial coating which was prepared by the incorporation of synthesised photoactive drug conjugates into pMEA-based hydrogels. Each of the photochemical conjugates were synthesised in good yield via DCC mediated or direct acid chloride esterification reactions. Conjugates were characterised using mass spectrometry and NMR spectroscopy in which a split in some proton signals was observed due to the use of a drug racemate in each synthesis, and the corresponsing diastereoisomeric character of the photoactive compounds.

To investigate the photochemical behaviour of the synthesised conjugates upon exposure to UV light and to assess the ability and rate at which a drug dose can be generated on demand, solutions of 2 and 3 were prepared in acetonitrile and exposed to increasing periods of UV irradiation. Fig. 3 illustrates the changes in acetonitrile solutions of the conjugates as the photochemical reaction progresses. Light exposure was shown to lead to depletion of the drug conjugate (decreasing band at 246 nm) while benzofuran formation and simultaneous drug regeneration was apparent through the increasing absorption band at 300 nm. In each case, the presence of isosbestic points at 233 nm and between 262–264 nm demonstrates the clean nature of the photolysis reaction. The rate of photolysis is analogous to the rate of benzofuran formation and hence can be calculated from the rate of the appearance of the 300 nm absorption band. Both reactions were shown to follow first order reaction kinetics and rate constants were calculated as 4.6 x 10−3 and 7.7 x 10−3 s−1 for 2 and 3 respectively. The more rapid photodissociation of the naproxen ester in comparison to its flurbiprofen counterpart may be explained by the extended π-conjugation that exists in this molecule, allowing higher excitation through more efficient absorption of 365 nm. This work has confirmed the ability to rapidly liberate drugs from the conjugates using UV irradiation, the amount of which is controlled by the duration of light exposure.

Successful UV triggered drug regeneration in solution warranted conjugate inclusion in a polymeric scaffold in order to investigate the potential for triggered release of drug from a biomaterial matrix. Careful consideration of the choice of matrix is essential to ensure the retention of the drug-DMB conjugate and photo-generated benzofuran side product while facilitating the release of the drug. In previous studies (11,12), a copolymer of HEMA and methyl methacrylate cross linked with EGDMA met these requirements by allowing drug to diffuse into surrounding medium upon irradiation yet retain the conjugate and the photochemical byproduct while in the hydrated state. With increasing markets for biomedical devices, materials that display high biocompatibility are increasing sought for their manufacture or, alternatively, surface modification. As such, the ability of pMEA to act as a successful housing for the photoactive conjugates was examined. pMEA is an amphiphilic polymer (16) comprised of a hydrophobic polyethylene chain and a mildly hydrophilic tail which is used commercially as a coating for artificial organs (17). The hydrophilicity of this polymer is reportedly lower than that of the pHEMA material used in our previous study as determined by sessile drop contact angle measurements, 47° vs 33° in the hydrated state (18). As a result, pMEA may be more conducive for retention of the drug conjugates without warranting the inclusion of MMA. Materials were prepared from MEA using EGDMA (1% w/w) as a crosslinker and were loaded with conjugates (5% w/w) prior to polymerisation. The transparency of the resulting polymeric film in theory should permit light to effectively penetrate the material allowing the photoreaction to take place.

The conjugate-loaded films were soaked in aqueous media in darkness to allow any residual unpolymerised material to elute from the matrix and subsequent analysis of the wash solutions showed the absence of both drug and conjugate. This demonstrates the viability of pMEA for housing of the conjugates, preventing elution and hydrolytic cleavage of the conjugates while embedded in the polymer, and that no conjugate or drug is released in the absence of light. This entrapment of drug-conjugate is not only essential to prevent diffusion of the conjugate from the device coating when in use, but is also crucial so as to ensure that should a device require submergence in water to activate the hydrophilic coating prior to insertion, the full loading will remain intact and available for release on demand.

Under light conditions, i.e. exposure to 365 nm irradiation, the ability of pMEA to act as polymeric scaffold for light-triggered drug delivery was shown. Sole diffusion of flurbiprofen and naproxen into the surrounding release media was established by UV spectroscopy illustrating the success of the photochemical reaction within the matrix, subsequent drug release capabilities and also the retention of the benzofuran by-product of the reaction. Fig. 4 illustrates the cumulative fraction of flurbiprofen and naproxen released from pMEA following irradiation periods of 10 and 30 min. In each case, prolonging the longevity of exposure is shown to significantly increase the amount of drug released from the matrix.