PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug

D.K. Sahana, G. Mittal, V. Bhardwaj, M.N.V. Ravi Kumar

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

The aim of present investigation was to screen different solvents for optimizing nanoparticle preparation in terms of particle size, entrapment efficiency, and finally, release behavior using a model drug estradiol. Nanoparticles were prepared following emulsion-diffusion-evaporation method using didodecyldimethyl ammonium bromide (DMAB) or polyvinyl alcohol (PVA) as stabilizers. Ethyl acetate (EA), acetone (ACE), chloroform (CHL), and dichloromethane (DCM) were used as organic solvents either individually or in combinations. DMAB when used as surfactant led to smaller particle size as compared to PVA irrespective of the solvents and combinations used, but on the other hand, PVA produced particles with higher entrapment when combinations of solvents used. DCM in combination with EA resulted in highest entrapment with both the stabilizers. All the formulations exhibited similar in vitro release profile (Zero order) irrespective of stabilizer (DMAB or PVA) used, however, the average release per day was higher in case of DCM formulations due to greater entrapment. In situ uptake studies suggest that smaller the particle size better is the uptake. The bioavailability from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg drug/rat. EA/DMAB (size 116.0 ± 2.6 nm) and DCM:EA 70:30/DMAB (size 253.0 ± 5.5 nm) showed the release for 9 and 5 days, respectively, whereas EA/PVA (size 279.3 ± 2.5 nm) released the drug over the periods of 3 days suggesting that particle size has significant role in determining the fate of nanoparticles in vivo. Histopathological examination revealed absence of any inflammatory response with the formulations under the studied period.
LanguageEnglish
Pages1530-1542
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume97
Issue number4
DOIs
Publication statusPublished - Jun 2008

Fingerprint

Polyvinyl Alcohol
Nanoparticles
Methylene Chloride
Estradiol
Particle Size
Pharmaceutical Preparations
Chloroform
Acetone
Emulsions
Surface-Active Agents
Biological Availability
Sprague Dawley Rats
ammonium bromide
In Vitro Techniques
polylactic acid-polyglycolic acid copolymer
ethyl acetate

Keywords

  • biodegradable
  • biocompatible
  • nanoparticle
  • oral delivery
  • organic solvents
  • pharmacology

Cite this

@article{85467e72ac6a4bbcb5908f586fe04a80,
title = "PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug",
abstract = "The aim of present investigation was to screen different solvents for optimizing nanoparticle preparation in terms of particle size, entrapment efficiency, and finally, release behavior using a model drug estradiol. Nanoparticles were prepared following emulsion-diffusion-evaporation method using didodecyldimethyl ammonium bromide (DMAB) or polyvinyl alcohol (PVA) as stabilizers. Ethyl acetate (EA), acetone (ACE), chloroform (CHL), and dichloromethane (DCM) were used as organic solvents either individually or in combinations. DMAB when used as surfactant led to smaller particle size as compared to PVA irrespective of the solvents and combinations used, but on the other hand, PVA produced particles with higher entrapment when combinations of solvents used. DCM in combination with EA resulted in highest entrapment with both the stabilizers. All the formulations exhibited similar in vitro release profile (Zero order) irrespective of stabilizer (DMAB or PVA) used, however, the average release per day was higher in case of DCM formulations due to greater entrapment. In situ uptake studies suggest that smaller the particle size better is the uptake. The bioavailability from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg drug/rat. EA/DMAB (size 116.0 ± 2.6 nm) and DCM:EA 70:30/DMAB (size 253.0 ± 5.5 nm) showed the release for 9 and 5 days, respectively, whereas EA/PVA (size 279.3 ± 2.5 nm) released the drug over the periods of 3 days suggesting that particle size has significant role in determining the fate of nanoparticles in vivo. Histopathological examination revealed absence of any inflammatory response with the formulations under the studied period.",
keywords = "biodegradable, biocompatible, nanoparticle, oral delivery, organic solvents, pharmacology",
author = "D.K. Sahana and G. Mittal and V. Bhardwaj and Kumar, {M.N.V. Ravi}",
year = "2008",
month = "6",
doi = "10.1002/jps.21158",
language = "English",
volume = "97",
pages = "1530--1542",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
number = "4",

}

PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug. / Sahana, D.K.; Mittal, G.; Bhardwaj, V.; Kumar, M.N.V. Ravi.

In: Journal of Pharmaceutical Sciences, Vol. 97, No. 4, 06.2008, p. 1530-1542.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug

AU - Sahana, D.K.

AU - Mittal, G.

AU - Bhardwaj, V.

AU - Kumar, M.N.V. Ravi

PY - 2008/6

Y1 - 2008/6

N2 - The aim of present investigation was to screen different solvents for optimizing nanoparticle preparation in terms of particle size, entrapment efficiency, and finally, release behavior using a model drug estradiol. Nanoparticles were prepared following emulsion-diffusion-evaporation method using didodecyldimethyl ammonium bromide (DMAB) or polyvinyl alcohol (PVA) as stabilizers. Ethyl acetate (EA), acetone (ACE), chloroform (CHL), and dichloromethane (DCM) were used as organic solvents either individually or in combinations. DMAB when used as surfactant led to smaller particle size as compared to PVA irrespective of the solvents and combinations used, but on the other hand, PVA produced particles with higher entrapment when combinations of solvents used. DCM in combination with EA resulted in highest entrapment with both the stabilizers. All the formulations exhibited similar in vitro release profile (Zero order) irrespective of stabilizer (DMAB or PVA) used, however, the average release per day was higher in case of DCM formulations due to greater entrapment. In situ uptake studies suggest that smaller the particle size better is the uptake. The bioavailability from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg drug/rat. EA/DMAB (size 116.0 ± 2.6 nm) and DCM:EA 70:30/DMAB (size 253.0 ± 5.5 nm) showed the release for 9 and 5 days, respectively, whereas EA/PVA (size 279.3 ± 2.5 nm) released the drug over the periods of 3 days suggesting that particle size has significant role in determining the fate of nanoparticles in vivo. Histopathological examination revealed absence of any inflammatory response with the formulations under the studied period.

AB - The aim of present investigation was to screen different solvents for optimizing nanoparticle preparation in terms of particle size, entrapment efficiency, and finally, release behavior using a model drug estradiol. Nanoparticles were prepared following emulsion-diffusion-evaporation method using didodecyldimethyl ammonium bromide (DMAB) or polyvinyl alcohol (PVA) as stabilizers. Ethyl acetate (EA), acetone (ACE), chloroform (CHL), and dichloromethane (DCM) were used as organic solvents either individually or in combinations. DMAB when used as surfactant led to smaller particle size as compared to PVA irrespective of the solvents and combinations used, but on the other hand, PVA produced particles with higher entrapment when combinations of solvents used. DCM in combination with EA resulted in highest entrapment with both the stabilizers. All the formulations exhibited similar in vitro release profile (Zero order) irrespective of stabilizer (DMAB or PVA) used, however, the average release per day was higher in case of DCM formulations due to greater entrapment. In situ uptake studies suggest that smaller the particle size better is the uptake. The bioavailability from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg drug/rat. EA/DMAB (size 116.0 ± 2.6 nm) and DCM:EA 70:30/DMAB (size 253.0 ± 5.5 nm) showed the release for 9 and 5 days, respectively, whereas EA/PVA (size 279.3 ± 2.5 nm) released the drug over the periods of 3 days suggesting that particle size has significant role in determining the fate of nanoparticles in vivo. Histopathological examination revealed absence of any inflammatory response with the formulations under the studied period.

KW - biodegradable

KW - biocompatible

KW - nanoparticle

KW - oral delivery

KW - organic solvents

KW - pharmacology

UR - http://dx.doi.org/10.1002/jps.21158

U2 - 10.1002/jps.21158

DO - 10.1002/jps.21158

M3 - Article

VL - 97

SP - 1530

EP - 1542

JO - Journal of Pharmaceutical Sciences

T2 - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 4

ER -