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®.

AS1411 Aptamer-Decorated Biodegradable Polyethylene Glycol–Poly(lactic-co-glycolic acid) Nanopolymersomes for the Targeted Delivery of Gemcitabine to Non–Small Cell Lung Cancer In Vitro

“…11Over the past few decades, there has been an increasing interest in the potential use of polymeric nanoparticles (NPs) as delivery vehicles for GEM, and studies have demonstrated that these nanocarriers can significantly enhance the anti-tumor efficiency of GEM and also reduce its systematic toxicities. [12][13][14][15] In this regard, Zhao et al 16 employed biocompatible lipid-polymer hybrid nanoparticles to co-deliver HIF1α siRNA and GEM for pancreatic cancer treatment in subcutaneous and orthotopic tumor models. The obtained results demonstrated the prolonged lifetime of GEM in the bloodstream and enhanced tumor tissue accumulation.…”

Biological nanoparticles carrying the Hmda-7 gene are effective in inhibiting pancreatic cancer in vitro and in vivo

“…As shown above, the BSA nanocarriers were spherical, with good dispersion and uniformed sizes. Their sizes of 115.6±12.3 nm were only slightly increased to 120.7±11.2 nm after 10 days of incubation at 25°C, indicating sufficient stability for in vitro and animal studies [ 15 ]. Gene therapy, a promising tool for treating pancreatic cancer [ 9 ], can be facilitated by the use of nanoparticles for delivery.…”