RESUMEN
Glioblastoma (GB) is the worst and most common primary brain tumor. Temozolomide (TMZ), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. However, at least 50% of TMZ treated patients do not respond to TMZ and the development of chemoresistance is a major problem. Here, we designed a lipid nanoemulsion containing a thermoresponsive polymer (poloxamer 407) aiming to improve TMZ release into the brain via nasal delivery. Increasing amounts of poloxamer 407 were added to preformed nanoemulsions (250 nm-range) obtained by spontaneous emulsification. The influence of the polymer concentration (from 2.5% to 12.5%) and temperature on viscosity was clearly evidenced. Such effect was also noticed on the mucoadhesiveness of formulations, as well as TMZ release rate and retention/permeation through nasal porcine mucosa using Franz-type diffusion cells. From these results, a formulation containing 10% of poloxamer (NTMZ-P10) was selected for further experiments by nasal route. A significantly higher TMZ amount was observed in the brain of rats from NTMZ-P10 in comparison with controls. Finally, our results show that formulation reduced significantly tumor growth by three-fold: 103.88 ± 43.67 mm3 (for NTMZ-P10) and 303.28 ± 95.27 mm3 (control). Overall, these results suggest the potential of the thermoresponsive formulation, administered by the non-invasive nasal route, as a future effective glioblastoma treatment.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Ratas , Animales , Porcinos , Temozolomida/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Administración Intranasal , Poloxámero/uso terapéutico , Línea Celular Tumoral , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Antineoplásicos Alquilantes/uso terapéuticoRESUMEN
This review gathers recent studies, patents, and clinical trials involving the nasal administration of peptide drugs to supply a panorama of developing nanomedicine advances in this field. Peptide drugs have been featured in the pharmaceutical market, due to their high efficacy, biological activity, and low immunogenicity. Pharmaceutical industries need technology to circumvent issues relating to peptide stability and bioavailability. The oral route offers very harsh and unfavourable conditions for peptide administration, while the parenteral route is inconvenient and risky for patients. Nasal administration is an attractive alternative, mainly when associated with nanotechnological approaches. Nanomedicines may improve the nasal administration of peptide drugs by providing protection for the macromolecules from enzymes while also increasing their time of retention and permeability in the nasal mucosa. Nanomedicines for nasal administration containing peptide drugs have been acclaimed for both prevention, and treatment, of infections, including the pandemic COVID-19, cancers, metabolic and neurodegenerative diseases.