Core-shell nanoparticulate formulation of gemcitabine

lyophilization, stability studies, and in vivo evaluation

Deepak Chitkara, Anupama Mittal, Ram I Mahato, Neeraj Kumar

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 Cmax, t1/2, 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 Cmax 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®.

Original languageEnglish (US)
Pages (from-to)439-451
Number of pages13
JournalDrug Delivery and Translational Research
Volume4
Issue number5-6
DOIs
StatePublished - Nov 18 2014

Fingerprint

gemcitabine
Freeze Drying
Nanoparticles
glycolic acid
Humidity
Particle Size
Area Under Curve
Breast Neoplasms
9,10-Dimethyl-1,2-benzanthracene
Trehalose
Bovine Serum Albumin
Inhibitory Concentration 50
Sprague Dawley Rats
Neoplasms
Water
Growth

Keywords

  • Breast cancer
  • Core-shell nanoparticles
  • Gemcitabine
  • Pharmacokinetics
  • Stability

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Core-shell nanoparticulate formulation of gemcitabine : lyophilization, stability studies, and in vivo evaluation. / Chitkara, Deepak; Mittal, Anupama; Mahato, Ram I; Kumar, Neeraj.

In: Drug Delivery and Translational Research, Vol. 4, No. 5-6, 18.11.2014, p. 439-451.

Research output: Contribution to journalArticle

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