Preclinical Evaluation of Polymeric Nanocomposite Containing Pregabalin for Sustained Release as Potential Therapy for Neuropathic Pain.

This study offers a novel oral pregabalin (PG)-loaded drug delivery system based on chitosan and hypromellose phthalate-based polymeric nanocomposite in order to treat neuropathic pain (PG-PN). PG-PN has a particle size of 432 ± 20 nm, a polydispersity index of 0.238 ± 0.001, a zeta potential of +19.0 ± 0.9 mV, a pH of 5.7 ± 0.06, and a spherical shape. Thermal and infrared spectroscopy confirmed nanocomposite generation. PG-PN pharmacokinetics was studied after a single oral dose in male Wistar rats. PG-PN showed greater distribution and clearance than free PG. The antinociceptive effect of PG-PN in neuropathic pain rats was tested by using the chronic constriction injury model. The parameter investigated was the mechanical nociceptive threshold measured by the von Frey filaments test; PG-PN showed a longer antinociceptive effect than free PG. The rota-rod and barbiturate sleep induction procedures were used to determine adverse effects; the criteria included motor deficit and sedative effects. PG-PN and free PG had plenty of motors. PG-PN exhibited a less sedative effect than free PG. By prolonging the antinociceptive effect and decreasing the unfavorable effects, polymeric nanocomposites with pregabalin have shown promise in treating neuropathic pain.

The liquid crystalline phase behaviour of a nasal formulation modifies the brain disposition of donepezil in rats in the treatment of Alzheimer's disease.

Although nanoparticles, polymeric micelles, liposomes, nanoemulsions, and microemulsions were extensively evaluated as formulations for nasal administration of drugs, lyotropic liquid crystal (LLC) mesophases have been few studied. The phase transition from a low-viscosity microemulsion to a more viscous LLC may improve the mucoadhesion of the formulation. Donepezil is a drug administered orally in the treatment of Alzheimer's disease, and with gastrointestinal side effects that are typical of acetylcholinesterase inhibitors. Based on this, donepezil administration by nasal pathway using a mucoadhesive LLC may be a feasible alternative. A colloidal formulation was selected from a ternary diagram, combining CETETH-10, oleic acid, and water (40:45:15, w/w). Donepezil was incorporated into the formulation, and the characterisation included in vitro studies, such as mucoadhesion and drug release. Pharmacokinetics in Wistar rats included evaluations by the nasal pathway with donepezil incorporated into microemulsion. A phase transition from an isotropic to an anisotropic system was observed after the swelling of the microemulsion with artificial nasal fluid (12-20 %). The release of donepezil in vitro occurred in a sustained manner. Significant levels of donepezil were achieved in the brain after nasal administration of the microemulsion, as a promising strategy for the treatment of Alzheimer's disease.

Toxicological analyses: analytical method validation for prevention or diagnosis.

The need for reliable results in Toxicological Analysis is recognized and required worldwide. The analytical validation ensures that a method will provide trustworthy information about a particular sample when applied in accordance with a predefined protocol, being able to determine a specific analyte at a distinct concentration range for a well-defined purpose. The driving force for developing method validation for bioanalytical projects comes from the regulatory agencies. Thus, the approach of this work is to present theoretical and practical aspects of method validation based on the analysis objective, whether for prevention or diagnosis. Although various legislative bodies accept differing interpretations of requirements for validation, the process for applying validation criteria should be adaptable for each scientific intent or analytical purpose.