title: Core-shell nanoparticulate formulation of gemcitabine: lyophilization, stability studies, and in vivo evaluation.
abstract: Core-shell nanoparticulate formulation of gemcitabine was prepared by incorporating gemcitabine in a hydrophilic bovine serum albumin (BSA) core surrounded by hydrophobic poly(DL-lactic acid-co-glycolic acid) (PLGA) shell with a particle size of 243 nm and encapsulation efficiency of 40.5 %. Prepared formulations were lyophilized, wherein several cryoprotectants were screened for product attributes such as cake appearance, reconstitution with water, and size constancy. Trehalose was screened as a lyoprotectant, which showed stability for 6 months at 5 °C and 25 °C/60 % relative humidity (RH) conditions. However, an increase in particle size was observed at accelerated conditions (40 °C/75 % RH). In vitro evaluation of these nano-formulations in MCF-7 breast cancer cells showed enhanced cellular uptake (90 %) as compared to GEMCITE® uptake (51 %) in 6 h along with reduced IC50 value at 72 h (16 μM versus 30 μM). In vivo studies in Sprague Dawley rats showed C max, t 1/2, and area under the curve (AUC) at 2.55 μg/ml, 13.6 h, and 28,322.5 μg/l/h, respectively, whereas GEMCITE® at the same dose showed significantly lower corresponding values at 1.94 μg/ml, 6.89 h, and 13,967 μg/l/h. In the same study, AUC and C max of inactive metabolite of gemcitabine (dFdU) were reduced by 33 and 42 %, respectively, for these nanoparticles compared to GEMCITE®. In 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer model, significantly reduced tumor growth was observed in gemcitabine-loaded-nanoparticle-treated animals compared with GEMCITE®-treated animal at equivalent dose (121 versus 243 % in 30 days). The results indicated that our core-shell nanoparticles are more effective for tumor reduction compared to marketed formulation of gemcitabine, GEMCITE®.
authors: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, 160 062, India.
authors: Deepak
authors: D
authors: Chitkara
authors: Anupama
authors: A
authors: Mittal
authors: Ram I
authors: RI
authors: Mahato
authors: Neeraj
authors: N
authors: Kumar