Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment

The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the <i>P</i>-gp expressed in the intestinal lumen. There...

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Autores principales:	Kanchan Kohli, Ali Mujtaba, Rozina Malik, Saima Amin, Md Sarfaraz Alam, Abuzer Ali, Md. Abul Barkat, Mohammad Javed Ansari
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	berberine alginate chitosan nanoparticles pharmacokinetic study Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/64cd336841514d73afa1fff816bbab57
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spelling	oai:doaj.org-article:64cd336841514d73afa1fff816bbab572021-11-11T18:48:35ZDevelopment of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment10.3390/polym132138332073-4360https://doaj.org/article/64cd336841514d73afa1fff816bbab572021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4360/13/21/3833https://doaj.org/toc/2073-4360The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the <i>P</i>-gp expressed in the intestinal lumen. Therefore, we aimed to design and fabricate a nanoparticulate system for delivery of BBR employing naturally derived biodegradable and biocompatible polymers, mainly chitosan and alginate, to enhance the oral bioavailability of BBR. A chitosan-alginate nanoparticle system loaded with BBR (BNPs) was formulated by ionic gelation method and was optimized by employing a three-factor, three-level Box-Behnken statistical design. BNPs were characterized for various physicochemical properties, ex vivo, and in vivo evaluations. The optimized BNPs were found to be 202.2 ± 4.9 nm in size, with 0.236 ± 0.02 of polydispersity index, zeta potential −14.8 ± 1.1 mV, and entrapment efficiency of 85.69 ± 2.6%. BNPs showed amorphous nature with no prominent peak in differential scanning calorimetry (DSC) investigation. Similarly, fourier-transform infrared spectroscopy (FTIR) studies did not reveal any interaction between BBR and excipients used. The drug release followed Higuchi kinetics, since these plots demonstrated the highest linearity (R<sup>2</sup> = 0.9636), and the mechanism of release was determined to be anomalous or non-Fickian in nature. An ex-vivo gut permeation study showed that BNPs were better internalized into the cells and more highly permeated through the intestine. Furthermore, in vivo pharmacokinetic analysis in female Wistar rats showed a 4.10−fold increase in the oral bioavailability of BBR from BNPs as compared to BBR suspension. With these findings, we have gained new insight into the effective delivery of poorly soluble and permeable drugs via a chitosan-alginate nanoparticle system to improve the therapeutic performance of an oral nanomedicine.Kanchan KohliAli MujtabaRozina MalikSaima AminMd Sarfaraz AlamAbuzer AliMd. Abul BarkatMohammad Javed AnsariMDPI AGarticleberberinealginatechitosannanoparticlespharmacokinetic studyOrganic chemistryQD241-441ENPolymers, Vol 13, Iss 3833, p 3833 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	berberine alginate chitosan nanoparticles pharmacokinetic study Organic chemistry QD241-441
spellingShingle	berberine alginate chitosan nanoparticles pharmacokinetic study Organic chemistry QD241-441 Kanchan Kohli Ali Mujtaba Rozina Malik Saima Amin Md Sarfaraz Alam Abuzer Ali Md. Abul Barkat Mohammad Javed Ansari Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment
description	The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the <i>P</i>-gp expressed in the intestinal lumen. Therefore, we aimed to design and fabricate a nanoparticulate system for delivery of BBR employing naturally derived biodegradable and biocompatible polymers, mainly chitosan and alginate, to enhance the oral bioavailability of BBR. A chitosan-alginate nanoparticle system loaded with BBR (BNPs) was formulated by ionic gelation method and was optimized by employing a three-factor, three-level Box-Behnken statistical design. BNPs were characterized for various physicochemical properties, ex vivo, and in vivo evaluations. The optimized BNPs were found to be 202.2 ± 4.9 nm in size, with 0.236 ± 0.02 of polydispersity index, zeta potential −14.8 ± 1.1 mV, and entrapment efficiency of 85.69 ± 2.6%. BNPs showed amorphous nature with no prominent peak in differential scanning calorimetry (DSC) investigation. Similarly, fourier-transform infrared spectroscopy (FTIR) studies did not reveal any interaction between BBR and excipients used. The drug release followed Higuchi kinetics, since these plots demonstrated the highest linearity (R<sup>2</sup> = 0.9636), and the mechanism of release was determined to be anomalous or non-Fickian in nature. An ex-vivo gut permeation study showed that BNPs were better internalized into the cells and more highly permeated through the intestine. Furthermore, in vivo pharmacokinetic analysis in female Wistar rats showed a 4.10−fold increase in the oral bioavailability of BBR from BNPs as compared to BBR suspension. With these findings, we have gained new insight into the effective delivery of poorly soluble and permeable drugs via a chitosan-alginate nanoparticle system to improve the therapeutic performance of an oral nanomedicine.
format	article
author	Kanchan Kohli Ali Mujtaba Rozina Malik Saima Amin Md Sarfaraz Alam Abuzer Ali Md. Abul Barkat Mohammad Javed Ansari
author_facet	Kanchan Kohli Ali Mujtaba Rozina Malik Saima Amin Md Sarfaraz Alam Abuzer Ali Md. Abul Barkat Mohammad Javed Ansari
author_sort	Kanchan Kohli
title	Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment
title_short	Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment
title_full	Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment
title_fullStr	Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment
title_full_unstemmed	Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment
title_sort	development of natural polysaccharide–based nanoparticles of berberine to enhance oral bioavailability: formulation, optimization, ex vivo, and in vivo assessment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/64cd336841514d73afa1fff816bbab57
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Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment

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