Nanostructured lipid carriers loaded with Halobetasol propionate for topical treatment of inflammation: Development, characterization, biopharmaceutical behavior and therapeutic efficacy of gel dosage forms.

The aim of this research was the development and characterization of three gel dosage forms of Halobetasol propionate loaded lipid nanoparticles (HB-NLC) for the treatment of inflammatory skin diseases. A Pluronic gel (Pl-HB-NLC), a Carbopol gel (Cb-HB-NLC) and a Cremigel (Cg-HB-NLC), were characterized for stability, swelling, degradation, porosity and rheology. The biopharmaceutical behavior of in vitro release and ex vivo permeation, along with microbiological stability were also evaluated. Tolerance and therapeutic efficacy were determined in vivo. The gels proved to have eudermic pH and to be effective to improve HB-NLC stability for more than 6 months. In vitro drug release profiles were adjusted to a first order (Pl-HB-NLC, Cg-HB-NLC) and hyperbola (Cb-HB-NLC) kinetic models, revealing sustained drug release. Ex vivo biopharmaceutical behavior showed slow drug penetration through skin, delaying the drug entrance into systemic circulation. The formulations were effective in reducing inflammation with a lower drug dose in comparison with existing treatments, obtaining the fastest effect when using Pl-HB-NLC. After application of the formulations in volunteers, no irritation, redness or edema reactions were detected, plus, an enhancement of the biomechanical properties of the skin was evidenciated. Therefore, the results indicate that these formulations are a suitable alternative to current treatments.

Ex Vivo Permeation of Carprofen Vehiculated by PLGA Nanoparticles through Porcine Mucous Membranes and Ophthalmic Tissues.

(1) Background: Carprofen (CP), 2-(6-chlorocarbazole) propionic acid, is used as an anti-inflammatory, analgesic and anti-pyretic agent and it belongs to the family of non-steroidal anti-inflammatory drugs (NSAIDs). CP has some adverse reactions in systemic administration; for this reason, topical administration with CP nanoparticles (CP-NPs) can be an optimal alternative. The main objective of this work is the investigation of ex vivo permeation of CP through different types of porcine mucous membranes (buccal, sublingual and vaginal) and ophthalmic tissues (cornea, sclera and conjunctiva) to compare the influence of CP-NPs formulation over a CP solution (CP-Solution). (2) Methods: The ex vivo permeation profiles were evaluated using Franz diffusion cells. Furthermore, in vivo studies were performed to verify that the formulations did not affect the cell structure and to establish the amount retained (Qr) in the tissues. (3) Results: Permeation of CP-NPs is more effective in terms of drug retention in almost all tissues (with the exception of sclera and sublingual). In vivo studies show that neither of the two formulations affects tissue structure, so both formulations are safe. (4) Conclusions: It was concluded that CP-NPs may be a useful tool for the topical treatment of local inflammation in veterinary and human medicine.