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

Pranesh Kumar,1 Ashok K Singh,1 Vinit Raj,1 Amit Rai,1 Amit K Keshari,1 Dinesh Kumar,2 Biswanath Maity,2 Anand Prakash,3 Sabyasachi Maiti,4 Sudipta Saha1 1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, India; 2Centre of Biomedical...

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Autores principales:	Kumar P, Singh AK, Raj V, Rai A, Keshari AK, Kumar D, Maity B, Prakash A, Maiti S, Saha S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Betulinic acid PLGA loaded nanoparticles Hep-G2 cells Hepatocellular carcinoma Caspase 3 and 8 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bf6697537ab144d2bae744a421602d36
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spelling	oai:doaj.org-article:bf6697537ab144d2bae744a421602d362021-12-02T02:42:31ZPoly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations1178-2013https://doaj.org/article/bf6697537ab144d2bae744a421602d362018-02-01T00:00:00Zhttps://www.dovepress.com/polylactic-co-glycolic-acid-loaded-nanoparticles--of-betulinic-acid-fo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Pranesh Kumar,1 Ashok K Singh,1 Vinit Raj,1 Amit Rai,1 Amit K Keshari,1 Dinesh Kumar,2 Biswanath Maity,2 Anand Prakash,3 Sabyasachi Maiti,4 Sudipta Saha1 1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, India; 2Centre of Biomedical Research, SGPGIMS Campus, Lucknow, Uttar Pradesh, India; 3Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, India; 4Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Anuppur, Madhya Pradesh, India 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 (t1/2), a higher maximum plasma concentration (Cmax) and took longer to reach the maximum plasma concentration (Tmax) 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. Keywords: betulinic acid, PLGA-loaded nanoparticles, HepG2 cells, hepatocellular carcinoma, caspase-3 and -8Kumar PSingh AKRaj VRai AKeshari AKKumar DMaity BPrakash AMaiti SSaha SDove Medical PressarticleBetulinic acidPLGA loaded nanoparticlesHep-G2 cellsHepatocellular carcinomaCaspase 3 and 8Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 975-990 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Betulinic acid PLGA loaded nanoparticles Hep-G2 cells Hepatocellular carcinoma Caspase 3 and 8 Medicine (General) R5-920
spellingShingle	Betulinic acid PLGA loaded nanoparticles Hep-G2 cells Hepatocellular carcinoma Caspase 3 and 8 Medicine (General) R5-920 Kumar P Singh AK Raj V Rai A Keshari AK Kumar D Maity B Prakash A Maiti S Saha S Poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations
description	Pranesh Kumar,1 Ashok K Singh,1 Vinit Raj,1 Amit Rai,1 Amit K Keshari,1 Dinesh Kumar,2 Biswanath Maity,2 Anand Prakash,3 Sabyasachi Maiti,4 Sudipta Saha1 1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, India; 2Centre of Biomedical Research, SGPGIMS Campus, Lucknow, Uttar Pradesh, India; 3Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, India; 4Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Anuppur, Madhya Pradesh, India 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 (t1/2), a higher maximum plasma concentration (Cmax) and took longer to reach the maximum plasma concentration (Tmax) 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. Keywords: betulinic acid, PLGA-loaded nanoparticles, HepG2 cells, hepatocellular carcinoma, caspase-3 and -8
format	article
author	Kumar P Singh AK Raj V Rai A Keshari AK Kumar D Maity B Prakash A Maiti S Saha S
author_facet	Kumar P Singh AK Raj V Rai A Keshari AK Kumar D Maity B Prakash A Maiti S Saha S
author_sort	Kumar P
title	Poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations
title_short	Poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations
title_full	Poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations
title_fullStr	Poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations
title_full_unstemmed	Poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations
title_sort	poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/bf6697537ab144d2bae744a421602d36
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Poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations

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