ABSTRACT
Pranoprofen (PF)-loaded nanoparticles (PF-F1NPs and PF-F2NPs) have been formulated into blank hydrogels (HG_PF-F1NPs and HG_PF-F1NPs) or into hydrogels composed of 3% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone), as innovative strategy to improve the biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (Pranoprofen, PF) for topical application. The purpose of this approach has been to increase the contact of PF with the skin, improve its retention in deeper layers, thus enhancing its anti-inflammatory and analgesic effects. The physicochemical characterization of the developed hydrogels showed a non-Newtonian behaviour, typical of semi-solid formulations for skin administration, with sustained release profile. The results obtained from ex vivo skin human permeation and in vivo anti-inflammatory efficacy studies suggest that topical application of HG_PF-F2NPs has been more effective in the treatment of oedema on the skin' surface in comparison to other hydrogels. No signs of skin irritancy have been detected for all the semi-solid formulations containing 0% or 3% azone.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Benzopyrans/administration & dosage , Drug Carriers/administration & dosage , Hydrogels/administration & dosage , Nanoparticles/administration & dosage , Propionates/administration & dosage , Adult , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Benzopyrans/chemistry , Benzopyrans/therapeutic use , Benzopyrans/toxicity , Drug Carriers/chemistry , Drug Carriers/therapeutic use , Drug Carriers/toxicity , Drug Liberation , Edema/chemically induced , Edema/drug therapy , Female , Humans , Hydrogels/chemistry , Hydrogels/therapeutic use , Hydrogels/toxicity , In Vitro Techniques , Lactic Acid/chemistry , Male , Mice , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Nanoparticles/toxicity , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Propionates/chemistry , Propionates/therapeutic use , Propionates/toxicity , Rabbits , Skin/metabolism , Skin Absorption , Skin Irritancy Tests , Tetradecanoylphorbol Acetate , ViscosityABSTRACT
Two optimized pranoprofen-loaded poly-l-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF-F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formulations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranoprofen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sustained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflammatory efficacy studies suggest that the ocular application of the hydrogels containing azone was more effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of ocular irritancy have been detected for the produced hydrogels.
