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A synthetic poly(amino acid), poly(aspartic acid) modified with thioethyl side groups, was studied as an in situ gelling and mucoadhesive dosage form. The chemical structure and the controllable, large thiol content of the polymer were confirmed using 1 H NMR spectroscopy and Ellman's assay. In situ gelation of aqueous polymer solutions was induced by oxidation and monitored using oscillation rheometry. The strength of mucoadhesion towards excised mucosa was characterised by tensile tests in ex vivo experiments. Release kinetics of ophthalmic antibiotic ofloxacin was studied from an in situ crosslinked hydrogel and a liquid formulation to prove the sustained release of the former.

Redox and pH responsive hydrogels were synthesized, which can serve as matrices for smart drug delivery systems exploiting the redox and pH gradients in the human body. Water soluble thiolated poly(aspartic acid), a biocompatible synthetic polymer, enables us to crosslink in water with a non-cleavable cross-linker, poly(ethylene glycol) diglycidyl ether. The permanent cross-linker establishes stable polymer hydrogels regardless of the redox environment, thus the gels swell but do not dissolve upon redox stimuli. The reversible response upon redox stimulus was induced by thiol-disulphide transformation inside the hydrogel. The degree of swelling and the stiffness of the macroscopic hydrogels were controlled by their chemical composition including thiol content and cross-linking ratio as well as the redox state of the hydrogels. The degree of swelling of the hydrogels showed strong pH dependence due to the polyelectrolyte nature of the polymer network. Release of a macromolecular model drug was considerably faster in reducing than in oxidising environment, which indicates the potential use of the synthesized hydrogels as redox responsive drug delivery systems. Nanogels were prepared in water-in-oil emulsion and displayed redox-responsive properties. The hydrodynamic diameter of the nanogels strongly increased upon the cleavage of the disulphide linkages in reducing solution without the disruption of the gels.

Thiolated poly(aspartic acid) is known as a good mucoadhesive polymer in aqueous ophthalmic formulations. In this paper, cyclodextrin-modified thiolated poly(aspartic acid) was synthesized for the incorporation of prednisolone, a lipophilic ophthalmic drug, in an aqueous in situ gellable mucoadhesive solution. This polymer combines the advantages of cyclodextrins and thiolated polymers. The formation of the cyclodextrin-drug complex in the gels was analyzed by X-ray powder diffraction. The ocular applicability of the polymer was characterized by means of physicochemical, rheological and drug diffusion tests. It was established that the chemical bonding of the cyclodextrin molecule did not affect the complexation of prednisolone, while the polymer solution preserved its in situ gellable and good mucoadhesive characteristics. The chemical immobilization of cyclodextrin modified the diffusion profile of prednisolone and prolonged drug release was observed. The combination of free and immobilized cyclodextrins provided the best release profile because the free complex can diffuse rapidly, while the bonded complex ensures a prolonged action.