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Drug Dev Ind Pharm ; 45(5): 745-753, 2019 May.
Article in English | MEDLINE | ID: mdl-30632800

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Carriers/chemistry , Pancreatic Neoplasms/drug therapy , Simvastatin/administration & dosage , Administration, Oral , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Biological Availability , Cell Line, Tumor , Cell Survival/drug effects , Deoxycytidine/administration & dosage , Deoxycytidine/pharmacokinetics , Drug Compounding/methods , Drug Liberation , Drug Screening Assays, Antitumor , Emulsions , Humans , Inhibitory Concentration 50 , Nanoparticles/chemistry , Pancreatic Neoplasms/pathology , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Rats , Rats, Wistar , Simvastatin/pharmacokinetics , Gemcitabine
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