RESUMEN
While some orally delivered diabetes peptides are moving to late development with standard formulations incorporating functional excipients, the demonstration of the value of nanotechnology in clinic is still at an early stage. The goal of this review is to compare these two drug delivery approaches from a physico-chemical and a biopharmaceutical standpoint in an attempt to define how nanotechnology-based products can be differentiated from standard oral dosage forms for oral bioavailability of diabetes peptides. Points to consider in a translational approach are outlined to seize the opportunities offered by a better understanding of both the intestinal barrier and of nano-carriers designed for oral delivery.
Asunto(s)
Diabetes Mellitus/metabolismo , Sistemas de Liberación de Medicamentos , Excipientes/química , Nanomedicina , Péptidos/administración & dosificación , Péptidos/farmacocinética , Investigación Biomédica Traslacional , Administración Oral , Animales , Excipientes/administración & dosificación , Excipientes/farmacocinética , HumanosRESUMEN
Cannabinoid CB2 PET tracers are considered as a promising alternative to PBR/TSPO tracers for the in-vivo imaging of neuroinflammation. We describe here the synthesis and characterization of compound 3, a new potent and brain penetrating CB2 ligand based on an original triazine template. The PET tracer [(18)F]-dideutero-3 was prepared in a three steps radiosynthesis, and demonstrated significant uptake in rhesus macaque and baboon brain with a maximum SUV of about 0.7-0.9g/mL, followed by a moderate washout over time.
Asunto(s)
Radioisótopos de Flúor/metabolismo , Tomografía de Emisión de Positrones , Receptor Cannabinoide CB2/metabolismo , Triazinas/metabolismo , Animales , Encéfalo/metabolismo , Radioisótopos de Flúor/química , Radioisótopos de Flúor/farmacocinética , Humanos , Ligandos , Macaca mulatta , Estructura Molecular , Papio , Triazinas/síntesis química , Triazinas/farmacocinéticaRESUMEN
A new series of 2,3-diarylpyrroles have been prepared and evaluated as CB(1) antagonists. Modulation of the topological polar surface area allowed the identification of high affinity peripherally-restricted CB(1) antagonists. Compound 11, obtained after further optimization of the metabolic profile displayed very low brain penetration, yet was able to reverse CP55940-induced gastrointestinal transit inhibition following oral administration.