A mucoadhesive in situ gel delivery system for paclitaxel

Saurabh Jauhari, Alekha K. Dash

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyccryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37°C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% ± 0.19%, 12.0% ± 0.98%, 31.7% ± 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% ± 4.35%, 44.2% ± 6.35%, and 97.1% ± 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.

Original languageEnglish
Article number53
JournalAAPS PharmSciTech
Volume7
Issue number2
DOIs
StatePublished - Jun 2 2006

Fingerprint

paclitaxel
Paclitaxel
Gels
gels
mucins
Mucins
Polysorbates
Colonic Neoplasms
cell lines
Pharmaceutical Preparations
Cell Line
drugs
Caco-2 Cells
antineoplastic agents
Chitosan
cells
chitosan
colorectal neoplasms
Surface-Active Agents
Citric Acid

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

A mucoadhesive in situ gel delivery system for paclitaxel. / Jauhari, Saurabh; Dash, Alekha K.

In: AAPS PharmSciTech, Vol. 7, No. 2, 53, 02.06.2006.

Research output: Contribution to journalArticle

@article{b8a142f5003f4824a12a4a83b9d68c8e,
title = "A mucoadhesive in situ gel delivery system for paclitaxel",
abstract = "MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyccryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18{\%}, 0.30{\%}, and 0.54{\%} (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37°C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61{\%} ± 0.19{\%}, 12.0{\%} ± 0.98{\%}, 31.7{\%} ± 0.40{\%} of PTX were released from 0.18{\%}, 0.30{\%}, and 0.54{\%} drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05{\%} wt/vol) in the dissolution medium, percentages of PTX released were 28.1{\%} ± 4.35{\%}, 44.2{\%} ± 6.35{\%}, and 97.1{\%} ± 1.22{\%}, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.",
author = "Saurabh Jauhari and Dash, {Alekha K.}",
year = "2006",
month = "6",
day = "2",
doi = "10.1208/pt070231",
language = "English",
volume = "7",
journal = "AAPS PharmSciTech",
issn = "1530-9932",
publisher = "American Association of Pharmaceutical Scientists",
number = "2",

}

TY - JOUR

T1 - A mucoadhesive in situ gel delivery system for paclitaxel

AU - Jauhari, Saurabh

AU - Dash, Alekha K.

PY - 2006/6/2

Y1 - 2006/6/2

N2 - MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyccryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37°C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% ± 0.19%, 12.0% ± 0.98%, 31.7% ± 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% ± 4.35%, 44.2% ± 6.35%, and 97.1% ± 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.

AB - MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyccryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37°C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% ± 0.19%, 12.0% ± 0.98%, 31.7% ± 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% ± 4.35%, 44.2% ± 6.35%, and 97.1% ± 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.

UR - http://www.scopus.com/inward/record.url?scp=33745108769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745108769&partnerID=8YFLogxK

U2 - 10.1208/pt070231

DO - 10.1208/pt070231

M3 - Article

VL - 7

JO - AAPS PharmSciTech

JF - AAPS PharmSciTech

SN - 1530-9932

IS - 2

M1 - 53

ER -