Gelatin microspheres crosslinked with D,L-glyceraldehyde as a potential drug delivery system: preparation, characterisation, in vitro and in vivo studies

To overcome the restriction in using crosslinked gelatin in the pharmaceuti cal field, D,L-glyceraldehyde (GAL), a non-toxic crosslinking agent, was pr oposed. Gelatin microspheres crosslinked with different concentrations of G AL (0.5, 1 or 2%, w/v) and for different time periods (1 or 24 h) were prep ared. The effect of the preparation variables was evaluated analysing the e xtent of crosslinking, the morphological aspect, the particle size and the swelling behaviour. To evaluate the pharmaceutical properties, an antihyper tensive drug, clonidine hydrochloride, was chosen as drug model and loaded into the microspheres. Either the increase of the crosslinker concentration or of the crosslinking time period decreased both the swelling and the in vitro drug release processes of the microspheres. After the subcutaneous in jection, the loaded microspheres crosslinked with the lowest GAL concentrat ion (0.5%. w/v) or for the shortest time period (1 h) showed a reduction of systolic blood pressure (SBP) similar to that recorded with a clonidine hy drochloride solution having the same drug concentration. Instead, the micro spheres crosslinked for 24 h with concentrations of GAL higher than 0.5% (w /v) produced a more gradual and sustained SEP reduction and the antihyperte nsive effect was maintained until 52-72 h. The biocompatibility studies sho wed that the microspheres crosslinked with GAL are well tolerated in vivo. These results suggest the potential application of gelatin microspheres cro sslinked with GAL as a suitable drug delivery system for the subcutaneous a dministration. (C) 2001 Elsevier Science B.V. All rights reserved.