RESUMO
Glioblastoma multiforme (GBM) is an extremely aggressive malignant brain tumor. Despite advances in treatment modalities, it remains largely incurable. This unfavorable prognosis for GBM is at least partly due to the lack of a successful drug delivery system across the blood-brain barrier (BBB). The delivery of drugs through nanomedicines combined with less invasive alternative therapies represents an important hope for the future of these incurable brain tumors. Whey protein nanocarriers represent promising strategy for targeted drug delivery to tumor cells by enhancing the drug's bioavailability and distribution, and reducing the body's response towards drug resistance. They have been extensively studied to find new alternatives for capacity to encapsulate different drugs and no need for cross-linkers. In this study, we report for the first time the incorporation and administration of Aluminum phthalocyanine chloride (AlClPc)-loaded whey protein drug delivery system (AlClPc-PDDS) for the treatment of glioblastoma brain cancer. This system was designed and optimized (with the use of the spray drying technique) to obtain the required particle size (in the range of 100 to 300 nm), zeta potential and drug loading. Our results suggest that we have developed a drug delivery system from a low-cost raw material and preparation method that is capable of incorporating hydrophobic drugs which, in combination with irradiation, cause photodamage to neoplasic cells, working as an effective adjuvant treatment for malignant glioma.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Portadores de Fármacos , Glioblastoma/tratamento farmacológico , Nanopartículas , Fármacos Fotossensibilizantes , Proteínas do Soro do Leite , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Indóis/química , Indóis/farmacocinética , Indóis/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Compostos Organometálicos/química , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/farmacologia , Proteínas do Soro do Leite/química , Proteínas do Soro do Leite/farmacocinética , Proteínas do Soro do Leite/farmacologiaRESUMO
Oral insulin administration is limited due to its degradation by proteases. The hormone was encapsulated in spheres made of either pure calcium alginate (ALG) or its association with whey protein isolate (WPI-ALG) in order to minimise loss in the stomach region while allowing liberation in the maximum absorption area, located in the intestine. Diffusion coefficients for both matrix compositions were determined in vitro for gastric pH (5.88 and 10.26 × 10-12 m2 s-1) and intestinal pH (21.11 and 79.29 × 10-12 m2 s-1). Higher initial insulin concentrations and lower diameters accelerated its release, confirming Fickian behaviour. The analytic model exhibited a good fit in most cases. Computer simulations revealed that ALG spheres are more convenient for oral administration because they release more insulin in the intestine than the WPI-ALG ones, thus supporting its therapeutic viability for the purpose of reducing stress in those who depend on insulin.