RESUMO
Present study explores native L-asparaginase encapsulated long-acting cross-linker-free PLGA-nanoformulation in an Ehrlich ascites tumor model. L-asparaginase-PLGA nanoparticles for tumor were prepared using a double emulsion solvent evaporation technique, optimized and validated by Box-Behnken Design. L-ASN-PNs showed a particle size of 195 nm ± 0.2 nm and a PDI of 0.2. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) techniques revealed its smooth morphology and elicited an in-vitro release of 80% of the drug, following the Higuchi drug release model. In-vivo studies of L-ASN-PNs on an Ehrlich ascites tumor (EAT) model were completed and compared with the standard medication of 5-fluorouracil (5-FU) treatment. L-ASN-PN treated mice showed a 51.15% decrease in tumor volume and 100% survival rate with no reduction in body weight, no haemotoxicity and no hepatotoxicity, as evident from the hematological parameters, and liver enzyme parameters that were well within the prescribed limits. Chemotherapy has severe side effects and restricted therapeutic success. Henceforth, the purported L-Asparaginase PLGA nanoparticles are a suitable entity for better tumor regression, intra-tumor accumulation and no hematological side-effects.
RESUMO
Despite the ongoing extensive research, cancer therapeutics still remains an area with unmet needs which is hampered by shortfall in the development of newer medicines. The present study discusses a nano-based combinational approach for treating solid tumor. Dual-loaded nanoparticles encapsulating gemcitabine HCl (GM) and simvastatin (SV) were fabricated by double emulsion solvent evaporation method and optimized. Optimized nanoparticles showed a particle size of 258 ± 2.4 nm, polydispersity index of 0.32 ± 0.052, and zeta potential of -12.5 mV. The size and the morphology of the particles wee further confirmed by transmission electron microscopy (TEM) and scanning electron microscopy, respectively of the particles. The entrapment efficiency of GM and SV in the nanoparticles was 38.5 ± 4.5% and 72.2 ± 5.6%, respectively. The in vitro release profile was studied for 60 h and showed Higuchi release pattern. The cell toxicity was done using MTT assay and lower IC50 was obtained with the nanoparticles as compared to the pure drug. The bioavailability of GM and SV in PLGA nanoparticles was enhanced by 1.4-fold and 1.3-fold respectively, compared to drug solution. The results revealed that co-delivery of GM and SV could be used for its oral delivery for the effective treatment of pancreatic cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Portadores de Fármacos/química , Neoplasias Pancreáticas/tratamento farmacológico , Sinvastatina/administração & dosagem , Administração Oral , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Disponibilidade Biológica , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacocinética , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Emulsões , Humanos , Concentração Inibidora 50 , Nanopartículas/química , Neoplasias Pancreáticas/patologia , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Ratos Wistar , Sinvastatina/farmacocinética , GencitabinaRESUMO
It is of interest to document data on morphometric (measurement of external form) analysis of maxillary and mandibular anterior teeth collected from a dental set up using mesio-distal (MD) dimension. The mesiodistal dimensions of all permanent anterior teeth (central incisor, lateral incisor and canine) of 25 males and 25 females patients were recorded using digital vernier calipers. Data were charted and statistical analysis was done using Mann Whitney U test. Data shows sexual dimorphism for every tooth between males and females. However, dimorphism was exhibited only in maxillary and mandibular canine, mandibular central incisors, and lateral incisor. Hence,odontometric parameters offer simple, reliable and cost-effective in forensic investigation for recording gender discrimination.