Long circulating PEGylated-chitosan nanoparticles of rosuvastatin calcium

Development and in vitro and in vivo evaluations

Mukundkumar Rameshbhai Hirpara, Jyothsna Manikkath, K. Sivakumar, Renuka S. Managuli, Karthik Gourishetti, Nandakumar Krishnadas, Rekha R. Shenoy, Belle Jayaprakash, Chamallamudi Mallikarjuna Rao, Srinivas Mutalik

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The aim of this study was to improve the pharmacokinetics and pharmacodynamics profile of rosuvastatin calcium by formulating long-circulating PEGylated chitosan nanoparticles (NPs). Chitosan was PEGylated by a carbodiimide mediated reaction, using a carboxylic acid derivative of PEG (polyethylene glycol). The NPs were optimised for particle size, polydispersity index, zeta potential and drug entrapment efficiency. In vitro drug release, pharmacokinetic and pharmacodynamics studies of the optimized nanoparticles were performed. PEGylation of chitosan was confirmed by FTIR analysis. Drug-excipient compatibility was studied by differential scanning calorimetry and FTIR analyses. Two batches of nanoparticles were optimized with particle size of <200 nm and entrapment efficiency of ≈14%. In vitro drug release studies revealed cumulative release of 14.07 ± 0.57% and 22.02 ± 0.81% of rosuvastatin over the period of 120 h, indicating appreciable sustained release of drug. TEM analysis showed the spherical structure of nanoparticles. Pharmacokinetic studies indicated that optimized NPs showed prolonged drug release over a period of 72 h. Pharmacodynamics studies in hyperlipidemic rat model demonstrated greater lipid-lowering capability of rosuvastatin nanoparticles in comparison with plain rosuvastatin. The nanoparticles demonstrated substantial prolonged delivery of the drug in vivo along with better therapeutic action, which could be potential drug delivery modality for ‘statins’.

Original languageEnglish
Pages (from-to)2190-2200
Number of pages11
JournalInternational Journal of Biological Macromolecules
Volume107
DOIs
Publication statusPublished - 01-02-2018

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Chitosan
Nanoparticles
Pharmacodynamics
Pharmacokinetics
Pharmaceutical Preparations
Fourier Transform Infrared Spectroscopy
Particle Size
Particle size
Carbodiimides
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Rosuvastatin Calcium
In Vitro Techniques
Excipients
Differential Scanning Calorimetry
Polydispersity
Zeta potential
Carboxylic Acids
Drug delivery
Rats
Differential scanning calorimetry

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

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title = "Long circulating PEGylated-chitosan nanoparticles of rosuvastatin calcium: Development and in vitro and in vivo evaluations",
abstract = "The aim of this study was to improve the pharmacokinetics and pharmacodynamics profile of rosuvastatin calcium by formulating long-circulating PEGylated chitosan nanoparticles (NPs). Chitosan was PEGylated by a carbodiimide mediated reaction, using a carboxylic acid derivative of PEG (polyethylene glycol). The NPs were optimised for particle size, polydispersity index, zeta potential and drug entrapment efficiency. In vitro drug release, pharmacokinetic and pharmacodynamics studies of the optimized nanoparticles were performed. PEGylation of chitosan was confirmed by FTIR analysis. Drug-excipient compatibility was studied by differential scanning calorimetry and FTIR analyses. Two batches of nanoparticles were optimized with particle size of <200 nm and entrapment efficiency of ≈14{\%}. In vitro drug release studies revealed cumulative release of 14.07 ± 0.57{\%} and 22.02 ± 0.81{\%} of rosuvastatin over the period of 120 h, indicating appreciable sustained release of drug. TEM analysis showed the spherical structure of nanoparticles. Pharmacokinetic studies indicated that optimized NPs showed prolonged drug release over a period of 72 h. Pharmacodynamics studies in hyperlipidemic rat model demonstrated greater lipid-lowering capability of rosuvastatin nanoparticles in comparison with plain rosuvastatin. The nanoparticles demonstrated substantial prolonged delivery of the drug in vivo along with better therapeutic action, which could be potential drug delivery modality for ‘statins’.",
author = "Hirpara, {Mukundkumar Rameshbhai} and Jyothsna Manikkath and K. Sivakumar and Managuli, {Renuka S.} and Karthik Gourishetti and Nandakumar Krishnadas and Shenoy, {Rekha R.} and Belle Jayaprakash and Rao, {Chamallamudi Mallikarjuna} and Srinivas Mutalik",
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Long circulating PEGylated-chitosan nanoparticles of rosuvastatin calcium : Development and in vitro and in vivo evaluations. / Hirpara, Mukundkumar Rameshbhai; Manikkath, Jyothsna; Sivakumar, K.; Managuli, Renuka S.; Gourishetti, Karthik; Krishnadas, Nandakumar; Shenoy, Rekha R.; Jayaprakash, Belle; Rao, Chamallamudi Mallikarjuna; Mutalik, Srinivas.

In: International Journal of Biological Macromolecules, Vol. 107, 01.02.2018, p. 2190-2200.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long circulating PEGylated-chitosan nanoparticles of rosuvastatin calcium

T2 - Development and in vitro and in vivo evaluations

AU - Hirpara, Mukundkumar Rameshbhai

AU - Manikkath, Jyothsna

AU - Sivakumar, K.

AU - Managuli, Renuka S.

AU - Gourishetti, Karthik

AU - Krishnadas, Nandakumar

AU - Shenoy, Rekha R.

AU - Jayaprakash, Belle

AU - Rao, Chamallamudi Mallikarjuna

AU - Mutalik, Srinivas

PY - 2018/2/1

Y1 - 2018/2/1

N2 - The aim of this study was to improve the pharmacokinetics and pharmacodynamics profile of rosuvastatin calcium by formulating long-circulating PEGylated chitosan nanoparticles (NPs). Chitosan was PEGylated by a carbodiimide mediated reaction, using a carboxylic acid derivative of PEG (polyethylene glycol). The NPs were optimised for particle size, polydispersity index, zeta potential and drug entrapment efficiency. In vitro drug release, pharmacokinetic and pharmacodynamics studies of the optimized nanoparticles were performed. PEGylation of chitosan was confirmed by FTIR analysis. Drug-excipient compatibility was studied by differential scanning calorimetry and FTIR analyses. Two batches of nanoparticles were optimized with particle size of <200 nm and entrapment efficiency of ≈14%. In vitro drug release studies revealed cumulative release of 14.07 ± 0.57% and 22.02 ± 0.81% of rosuvastatin over the period of 120 h, indicating appreciable sustained release of drug. TEM analysis showed the spherical structure of nanoparticles. Pharmacokinetic studies indicated that optimized NPs showed prolonged drug release over a period of 72 h. Pharmacodynamics studies in hyperlipidemic rat model demonstrated greater lipid-lowering capability of rosuvastatin nanoparticles in comparison with plain rosuvastatin. The nanoparticles demonstrated substantial prolonged delivery of the drug in vivo along with better therapeutic action, which could be potential drug delivery modality for ‘statins’.

AB - The aim of this study was to improve the pharmacokinetics and pharmacodynamics profile of rosuvastatin calcium by formulating long-circulating PEGylated chitosan nanoparticles (NPs). Chitosan was PEGylated by a carbodiimide mediated reaction, using a carboxylic acid derivative of PEG (polyethylene glycol). The NPs were optimised for particle size, polydispersity index, zeta potential and drug entrapment efficiency. In vitro drug release, pharmacokinetic and pharmacodynamics studies of the optimized nanoparticles were performed. PEGylation of chitosan was confirmed by FTIR analysis. Drug-excipient compatibility was studied by differential scanning calorimetry and FTIR analyses. Two batches of nanoparticles were optimized with particle size of <200 nm and entrapment efficiency of ≈14%. In vitro drug release studies revealed cumulative release of 14.07 ± 0.57% and 22.02 ± 0.81% of rosuvastatin over the period of 120 h, indicating appreciable sustained release of drug. TEM analysis showed the spherical structure of nanoparticles. Pharmacokinetic studies indicated that optimized NPs showed prolonged drug release over a period of 72 h. Pharmacodynamics studies in hyperlipidemic rat model demonstrated greater lipid-lowering capability of rosuvastatin nanoparticles in comparison with plain rosuvastatin. The nanoparticles demonstrated substantial prolonged delivery of the drug in vivo along with better therapeutic action, which could be potential drug delivery modality for ‘statins’.

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M3 - Article

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EP - 2200

JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

SN - 0141-8130

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