RESUMO
Chitosan/chondroitin sulfate (CHT/CS) curcumin-charged hydrogels were prepared through polyelectrolytic complexation (PEC) following two methodologies (PEC-CUR and PEC-T-CUR) and were applied on apoptosis of HeLa, HT29 and PC3 cancer cells. PEC-T-CUR (ionic liquid (IL) mixed using ultraturrax homogenizer) results show to be far better than for PEC-CUR (IL mixed using magnetic stirring), with IC50 being improved 5.13 times to HeLa cancer cells (from 1675.2 to 326.7 µg mL-1). PECs produced by this methodology presented favorable characteristics, such as particle size, hydrophobicity, pH swelling. Beyond this, the IL was quantitatively recovered in both cases. CUR entrapment levels were hugely loaded into PEC at around 100%. Swelling, dissolution/degradation, and pHpzc assays showed that PECs may positively act in several environments, releasing the CUR, the CHT and CS as well. Characterization through FTIR, SEM, TEM, TGA, DSC, and WAXS confirmed CUR presence in both types of PECs, and cytotoxic studies showed the significant anticancer effects of CUR-containing PECs.
Assuntos
Antineoplásicos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Quitosana/química , Curcumina/química , Portadores de Fármacos/química , Hidrogéis/química , Líquidos Iônicos/química , Nanopartículas/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sulfatos de Condroitina/química , Células HT29 , Células HeLa , Humanos , Hidrogéis/farmacologia , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Células PC-3 , Tamanho da Partícula , Polieletrólitos/químicaRESUMO
Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi), an intracellular pathogen that causes significant morbidity and death among millions in the Americas from Canada to Argentina. Current therapy involves oral administration of the nitroimidazole benznidazole (BNZ), which has serious side effects that often necessitate cessation of treatment. To both avoid off-target side effects and reduce the necessary dosage of BNZ, we packaged the drug within poly(ethylene glycol)-block-poly(propylene sulfide) polymersomes (BNZ-PSs). We show that these vesicular nanocarriers enhanced intracellular delivery to phagocytic cells and tested this formulation in a mouse model of T. cruzi infection. BNZ-PS is not only nontoxic but also significantly more potent than free BNZ, effectively reducing parasitemia, intracellular infection, and tissue parasitosis at a 466-fold lower dose of BNZ. We conclude that BNZ-PS was superior to BNZ for treatment of T. cruzi infection in mice and that further modifications of this nanocarrier formulation could lead to a wide range of custom controlled delivery applications for improved treatment of Chagas disease in humans.
Assuntos
Doença de Chagas/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas , Nitroimidazóis/administração & dosagem , Fagócitos/parasitologia , Tripanossomicidas/administração & dosagem , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Portadores de Fármacos , Camundongos , Nitroimidazóis/farmacologia , Fagócitos/efeitos dos fármacos , Polietilenoglicóis , Sulfetos , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Thermosensitive hydrogels based on chitosan/pectin (CS/Pec) and CS/Pec/gold nanoparticles (CS/Pec/AuNPs) were successfully prepared with different AuNP levels. Using a tilting method, gelation temperature was demonstrated to decrease when the amount of AuNPs increased and pectin concentrations decreased. The presence of AuNPs in the CS/Pec composite was evaluated via WAXS and UV-vis techniques, while SEM analysis assessed the average size of pores (350-600µm). All samples were extremely cytocompatible with many cell types, such as normal kidney epithelial cells (VERO cells), epithelial colorectal adenocarcinoma cells (HT-29 cells), HPV-16 positive human cervical tumour cells (SiHa cells), kidney epithelial cells (LLCMK2 cells) and murine macrophage cells (J774A1 cells). Cell viability assays using the MTT method upon mouse preosteoblastic cells (MC3T3-E1 cells) showed that CS/Pec and CS/Pec/AuNPs composites had the potential to foster proliferation and growth of bone cells, making them possible stimulators for reconstruction of bone tissues.