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.

Lipid Nanoparticles as Carriers for the Treatment of Neurodegeneration Associated with Alzheimer's Disease and Glaucoma: Present and Future Challenges.

Glaucoma constitutes the second cause of blindness worldwide and it is considered a neurodegenerative disorder. In this sense, Alzheimer's disease, which is the most common type of dementia, also causes neurodegeneration. The association between both diseases remains unknown although it has been hypothesised that a possible connection might exist and it will be analysed throughout the review. In this sense, nanoparticulate systems and specially, lipid nanoparticles could be the key for effective neuroprotection. Lipid nanoparticles are the most recent type of drug nanoparticulate systems. These nanoparticles have shown great potential to encapsulate hydrophobic drugs increasing their bioavailability and being able to deliver them to the target tissue. In addition, they have shown great potential for ocular drug delivery. This review explores the most recent strategies employing lipid nanoparticles for AD and glaucoma.

Ocular penetration of fluorometholone-loaded PEG-PLGA nanoparticles functionalized with cell-penetrating peptides.

Aim: Development of fluorometholone-loaded PEG-PLGA nanoparticles (NPs) functionalized with cell-penetrating peptides (CPPs) for the treatment of ocular inflammatory disorders. Materials & methods: Synthesized polymers and peptides were used for elaboration of functionalized NPs, which were characterized physicochemically. Cytotoxicity and ability to modulate the expression of proinflammatory cytokines were evaluated in vitro using human corneal epithelial cells (HCE-2). NPs uptake was assayed in both in vitro and in vivo models. Results: NPs showed physicochemical characteristics suitable for ocular administration without evidence of cytotoxicity. TAT-NPs and G2-NPs were internalized and displayed anti-inflammatory activity in both HCE-2 cells and mouse eye. Conclusion: TAT-NPs and G2-NPs could be considered a novel strategy for the treatment of ocular inflammatory diseases of the anterior and posterior segment.

Thiazolidinedione as an alternative to facilitate oral administration in geriatric patients with Alzheimer's disease.

Pioglitazone (PGZ) is a member of the thiazolidinedione (TZDs) family of drugs and it is primarily used to treat type 2 diabetes. Previous studies have reported anti-inflammatory and neuroprotective effects in the central nervous system. Building on this, the aim of this study was to develop an oral solution of PGZ (PGZ-SOL) as an alternative treatment for geriatric patients with Alzheimer's disease (AD). Solubility of PGZ was evaluated to establish the solution composition. Parameters determined were pH, rheology, extensibility and retention time. In vitro diffusion kinetic profile and ex vivo permeation studies were carried out in Franz diffusion cells using buccal, sublingual, nasal and intestinal mucosae. The toxicity of PGZ-SOL was evaluated by in vivo model using BALB/c mice. PGZ-SOL exhibited a Newtonian behavior as well as physical and chemical stability during a period of three months. The diffusion profile of PGZ from formulation followed a first-order kinetic model. The biopharmaceutical parameters revealed high permeability of PGZ via intestinal mucosa. Finally, oral administration of PGZ-SOL did not cause damage of buccal, sublingual and intestinal mucosae which suggests that this formulation is a viable alternative for AD treatment in geriatric populations with difficulty swallowing conventional solid dosage forms.

In-situ forming gels containing fluorometholone-loaded polymeric nanoparticles for ocular inflammatory conditions.

Thermosensitive gels have been developed and optimized in such a way that they become gels at corneal temperature and with a viscosity that allows the adequate release of the Fluorometholone (FMT)-loaded PLGA nanoparticles (NPs) in order to improve ocular anti-inflammatory efficacy against a commercial formulation. It has been shown that gels avoid burst release of the drug in the first hours with a slow and increasing profile after administration. NPs have maintained their average size and spherical shape within the gels as confirmed by transmission electron microscopy (TEM). In turn, the in-situ gelling of the formulations allows the administration in eye drops dosage form due to its state of sol at temperatures below 25 °C. Ocular tolerance studies have shown that no formulation causes eye irritation. The administration of the developed formulations has improved the precorneal residence time reflected in the ocular bioavailability, where deep tissues as aqueous humour and crystalline were reached. In conclusion, the use of thermosensitive gels for the topical application of NPs has demonstrated their effectiveness in the acute and preventive treatment of ocular inflammatory conditions.

Development of fluorometholone-loaded PLGA nanoparticles for treatment of inflammatory disorders of anterior and posterior segments of the eye.

The main objective of this study was the development and optimization of fluorometholone-loaded PLGA nanoparticles for the treatment of inflammatory conditions of the eye. Design of experiments was used to obtain nanoparticles with the best physicochemical characteristics. The optimized nanoparticles containing 1.5 mg·mL-1 of fluorometholone showed a negative surface charge (-30 mV) and an average size below 200 nm being suitable for ocular administration. Drug-polymer interaction studies confirmed no new bonds were formed during the synthesis. Nanoparticles performance was assessed with biopharmaceutical behavior studies, ocular tolerance, anti-inflammatory efficacy and bioavailability. The biopharmaceutical behavior of the drug from nanoparticles was adjusted to hyperbola order showing a significantly greater permeation in the cornea than in the sclera. The optimized formulation had significantly greater anti-inflammatory effects than the commercial formulation. In addition, nanoparticles increased drug penetration toward the vitreous. Polymeric nanoparticles of fluorometholone could provide a suitable alternative for the treatment of inflammatory disorders of the anterior and posterior segments of the eye against of conventional topical formulations.