RESUMO
Glioblastoma (GBM) is the most common brain cancer characterized by aggressive and infiltrated tumors. For this, hybrid biopolymer-lipid nanoparticles coated with biopolymers such as chitosan and lipidic nanocarriers (LN) loaded with a photosensitizer (AlClPc) can be used for GBM photodynamic therapy. The chitosan-coated LN exhibited stable physicochemical characteristics and presented as an excellent lipid nanocarrier with highly efficiently encapsulated photosensitizer chloro-aluminum phthalocyanine (AlClPc). LN(AlClPc)Ct0.1% in the presence of light produced more reactive oxygen species and reduced brain tumor cell viability and proliferation. Confirm the effects of in vivo LN applications with photodynamic therapy confirmed that the total brain tumor area decreased without systemic toxicity in mice. These results suggest a promising strategy for future clinical applications to improve brain cancer treatment.
Assuntos
Neoplasias Encefálicas , Quitosana , Glioblastoma , Nanopartículas , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Glioblastoma/tratamento farmacológico , Quitosana/uso terapêutico , Fotoquimioterapia/métodos , Nanopartículas/química , Neoplasias Encefálicas/tratamento farmacológico , Lipídeos , Linhagem Celular TumoralRESUMO
Parkinson's disease (PD) is a progressive and chronic neurodegenerative disease of the central nervous system. Early treatment for PD is efficient; however, long-term systemic medication commonly leads to deleterious side-effects. Strategies that enable more selective drug delivery to the brain using smaller dosages, while crossing the complex brain-blood barrier (BBB), are highly desirable to ensure treatment efficacy and decrease/avoid unwanted outcomes. Our goal was to design and test the neurotherapeutic potential of a forefront nanoparticle-based technology composed of albumin/PLGA nanosystems loaded with dopamine (ALNP-DA) in 6-OHDA PD mice model. ALNP-DA effectively crossed the BBB, replenishing dopamine at the nigrostriatal pathway, resulting in significant motor symptom improvement when compared to Lesioned and L-DOPA groups. Notably, ALNP-DA (20 mg/animal dose) additionally up-regulated and restored motor coordination, balance, and sensorimotor performance to non-lesioned (Sham) animal level. Overall, ALNPs represent an innovative, non-invasive nano-therapeutical strategy for PD, considering its efficacy to circumvent the BBB and ultimately deliver the drug of interest to the brain.
Assuntos
Barreira Hematoencefálica/metabolismo , Dopamina/administração & dosagem , Dopamina/farmacocinética , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Humanos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Nanotecnologia , Oxidopamina/toxicidade , Transtornos Parkinsonianos/induzido quimicamente , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/químicaRESUMO
Breast cancer is the most common neoplasm among women but thanks to innovative therapies, patients' prognosis has considerably improved. In this aspect, nanotechnology has been applied for cancer therapy aiming to reduce its usual side effects. In this study we aimed to evaluate the effects of nanoemulsions containing photosensitizer and chemotherapeutic agents associated with photodynamic therapy in a breast cancer in vivo model. Our results showed that synergistic treatments in which chloroaluminum phthalocyanine (NE-Pc) administered together with Doxorubicin (Dox) in the presence of laser irradiation (NE-PcDoxo + PDT) led to a reduction of 4 T1 induced breast cancer in mice, decline of tumor VEGF expression, increase in Caspase-3 expression, tissue necrosis and massive decrease in proliferative cells, as shown by Ki67 immunostaining. Furthermore, this associated treatment induced overexpression of apoptotic genes ABL1, CD70, CRADD, FASL, and NME5 and a reduction in expression of anticancer drug target genes CDK2, ERBB2, FIGF, IGF2, PARP4 and PGR. These results validate this treatment as a promising alternative to improve the currently applied anticancer strategies.
Assuntos
Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Doxorrubicina/química , Indóis/química , Nanocápsulas/química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Animais , Antineoplásicos/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Doxorrubicina/farmacologia , Descoberta de Drogas , Quimioterapia Combinada , Emulsões/química , Feminino , Humanos , Indóis/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
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
OBJECTIVES: This clinical study was developed to primarily evaluate the Complete Cytopathological Response Rate of Cervical Intraepithelial Neoplasms to PDT using chitosan nanocapsules containing Chlorocyan-aluminum phthalocyanine as a photoactive agent. Analyses of the Free Recurrence Interval, toxicity profile (immediate and late), and complications (immediate and late), were secondarily analyzed. METHODS: This study was previously approved by the National Council of Ethics in Research of Brazil (CONEP), on May 28, 2014, under case number 19182113.4.0000.5009. On the surface of the cervix of each selected patient was applied one mL of the formulated gel, and after 30 min, the light was applied. Reports or the identification of adverse effects and/or complications were observed in follow-up visits, in addition to the collection of cervical oncotic cytology. RESULTS: Out of the total group, 11 (91.7%) primarily treated patients evolved with negative cervical oncotic cytology as soon as in the first evaluation following treatment, and one did not achieve any therapeutic benefit, even after reapplication. Two patients with initially positive response presented cytological recurrence determined by histopathology. A new round of PDT was developed, and both evolved with cytological remission three weeks later, remaining negative until the last follow-up. No important side effects were observed in all the patients. CONCLUSIONS: Our trial demonstrates that treatment of CIN 1 and 2 lesions using our PDT formulation is feasible and safe. Large randomized clinical trials are required to establish efficacy.