Effect of fluidizing agents on paclitaxel penetration in cervical cancerous monolayer membranes.
The aim of this study was to compare modulation of paclitaxel penetration in cancerous and normal cervical monolayers by four fluidizing agents: PCPG (9:1 DPPC:PG), PCPE (9:1 DPPC:DOPE), ALEC (7:3 DPPC:PG) and Exosurf (13.5:1.5:1.0 DPPC:hexadecanol:tyloxapol). Presence of the fluidizing agents improved drug penetration significantly. PCPG and PCPE were promising penetration enhancers. PCPG 0.1% caused 3.8- and 1.7-fold higher maximum increments in surface pressure due to drug penetration, (Delta pi)(max), than the control in cancerous and normal monolayers, respectively, at 20 mN/m. In cancerous monolayer at 20 mN/m, presence of 0.1%, 0.5%, 1%, 5% and 10% PCPE produced 3.4-, 5.7-, 7.4-, 9.6- and 9.8-fold higher drug penetration compared to the control monolayer without PCPE, respectively. In cancerous monolayer at 20 mN/m, PCPG and PCPE liposomes having 1 mg lipid gave 2.1 and 3.6 times higher (Delta pi)(max )compared to the control, respectively. Further, the liposomal drug penetration was found to be directly proportional to the liposomal lipid content. The effect of the fluidizing agents was confirmed by increased calcein release from model cervical cancer liposomes. These results may have implications in using the above biocompatible lipids and surfactants as penetration enhancers along with anticancer drugs or as carriers for liposomal formulations of anticancer drugs for improved membrane penetration.
Preetha
A
A
School of Biosciences and Bioengineering, Indian Institute of Technology, Mumbai, 400076, India.
Huilgol
N
N
Banerjee
R
R
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000494:pharmacology; D005260:Female; D005452:Fluoresceins / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008560:Membrane Fluidity / Q000187:drug effects*; D008567:Membranes, Artificial; D008954:Models, Biological; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010743:Phospholipids / Q000494:pharmacology; D010767:Phosphorylcholine / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D005233:Fatty Alcohols; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D008567:Membranes, Artificial; D010743:Phospholipids; D013501:Surface-Active Agents; C068829:artificial lung expanding compound; D010767:Phosphorylcholine; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; D017239:Paclitaxel; C007740:fluorexon
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