Effect of Fluidizing Agents on Paclitaxel Penetration in Cervical Cancerous Monolayer Membranes

Abstract

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.

Biophysical Interactions with Model Lipid Membranes: Applications in Drug Discovery and Drug Delivery

“…Therefore, understanding the role of these interactions on the pharmacokinetic properties of drugs is critical in developing potent drugs. A variety of drugsantibiotics, − antihypertensive drugs, , antifungal drugs, antipsychotic drugs , and anticancer agents − have been investigated for their interaction with lipids using different biophysical techniques.…”

Interactions of bioactive molecules & nanomaterials with Langmuir monolayers as cell membrane models

“…PG, PE) into DPPC films [199]. Paclitaxel was found to interact with DPPC, destabilizing the monolayer by increasing acyl chain mobility, as proven with FTIR experiments [200], leading to fluidization [200,201], which was also observed on DMPC monolayers [202].…”

Linking genotoxicity and cytotoxicity with membrane fluidity: A comparative study in ovarian cancer cell lines following exposure to auranofin

“…Drugs cross the plasma membrane barrier by diffusion and diffusion rate of drugs is lower through a higher ordered rigid membrane compared to a lesser ordered fluid membrane (1). Pharmaceutical intervention to fluidise the membrane had shown that the drug could effectively diffuse into the membrane and could reverse the resistance (7). A rapid increase in plasma membrane fluidity has been reported in cisplatin treated tumour cells (21).…”

“…Interestingly, the threshold concentration of internalised doxorubicin is the same for both resistant and sensitive cells suggesting drug uptake could be a major factor deciding the sensitivity of cancer cells (2). Modulation of membrane fluidity by pharmacological agents has been demonstrated to increase the drug uptake and thereby sensitivity of cancer cells to chemotherapeutic agents (7). The membrane lipid analysis of cisplatin and doxorubicin resistant breast cancer cells showed a high content of cholesterol and sphingomyelins which results in membrane rigidity (4).…”