Poly(lactic-<em>co</em>-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations

Abstract

Purpose The application of betulinic acid (B), a potent antineoplastic agent, is limited due to poor bioavailability, short plasma half-life and inappropriate tissue distribution. Thus, we aimed to prepare novel 50:50 poly(lactic- co -glycolic acid) (PLGA)-loaded B nanoparticles (BNP) and to compare its anti-hepatocellular carcinoma (HCC) activity with parent B. Methods BNP were synthesized and characterized using different methods such as scanning electron microscopy (SEM), fourier-transform infrared (FTIR) spectrometry and particle size analyses. Particle size of BNP was optimized through the application of the stabilizer, polyvinyl alcohol (PVA). The anti-HCC response was evaluated through in vitro cell line study using Hep-G2 cells, confocal microscopy, in vivo oral pharmacokinetics and animal studies. Further, quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was conducted to observe the changes in the expression of specific genes. Results Particle size of BNP was optimized through the application of the stabilizer, polyvinyl alcohol. Physicochemical characterization exhibited particle size of 257.1 nm with zeta potential −0.170 mV (optimized batch B, BNP). SEM and FTIR analyses of BNP showed that cylindrical particles of B converted to spherical particles in BNP and there were no interaction between B and used polymers. The release study of optimized BNP was highest (≥80%) than any other formulation. Later, in vitro cell culture analysis using Hep-G2 cells and confocal microscopy studies revealed that BNP had the highest inhibition and penetration properties than parent B. Oral pharmacokinetics studies using albino Wistar rats at single 100 mg dose again exhibited BNP had the higher 50% of plasma concentration (t 1/2 ), a higher maximum plasma concentration ( C max ) and took longer to reach the maximum plasma concentration (T max ) than parent B. Next, our in vivo study using nitrosodiethyl amine (NDEA)-induced HCC model documented BNP decreased in number of nodules, restored body weight, oxidative stress parameters, liver marker enzymes and histological architecture than parent B. Lastly, qRT-PCR studies further demonstrated that anti-HCC properties of BNP may be due to over expression of antiapoptotic caspases i.e., caspase 3 and 8. Conclusion The prepared BNP showed a better therapeutic response against HCC and could be attributed as future candidate molecule for HCC treatment.

Cherry Extract from Prunus avium L. to Improve the Resistance of Endothelial Cells to Oxidative Stress: Mucoadhesive Chitosan vs. Poly(lactic-co-glycolic acid) Nanoparticles

“…Poly(lactic- co -glycolic acid) (PLGA) is another polymer that is widely and successfully used to encapsulate extracts of natural products via different techniques. PLGA is a synthetic polymer approved by the United States (US) Food and Drug Administration (FDA) and European Medicine Agency (EMA) for the production of polymeric biocompatible and biodegradable NPs encapsulating polyphenol-rich fruits and other nutraceuticals [15,16,17,18,19].…”

Effect of Reaction Temperature on Shape Evolution of Palladium Nanoparticles and Their Cytotoxicity against A-549 Lung Cancer Cells

“…22 Kumar et al prepared (polylactic- co -glycolic acid)-loaded nanoparticle betulinic acid for improved treatment of hepatic cancer and showed in vitro and in vivo evaluation. 23 Several structural modifications have been proposed to improve biomedical efficiency of Pd nanoparticles. 22,24 Porous Pd nanoparticles (22.8 nm) were also recently reported as attractive PT agents with a PT conversion efficiency as high as 93.4%, which is comparable to typical Au nanorods.…”

Extracts of Clove (Syzygium aromaticum) Potentiate FMSP-Nanoparticles Induced Cell Death in MCF-7 Cells

“…The size and concentration of nanoparticles play very crucial role in inducing therapeutic effects on cancer cells and variations in the concentration and sizes of nanoparticles do produce inconsistent effects. Most of the studies have used different concentrations of nanoparticles ranging from 10 ug/ml to 200 ug/ml to obtain desirable therapeutic effects [ 38 – 43 ]. The size of the nanoparticles is used ranged between 10 nM and 200 nM on the cancer cells [ 38 , 42 ].…”