Lipid Drug Carriers for Cancer Therapeutics: An Insight into Lymphatic Targeting, P-gp, CYP3A4 Modulation and Bioavailability Enhancement.

Shashank Chaturvedi,Anurag Verma,Vikas Anand Saharan

doi:10.34172/apb.2020.064

Shashank Chaturvedi, Anurag Verma + Show 1 more

Open Access

https://doi.org/10.34172/apb.2020.064

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Abstract

In the treatment of cancer, chemotherapy plays an important role though the efficacy of anti-cancer drug administered orally is limited, due to their poor solubility in physiological medium, inability to cross biological membrane, high Para-glycoprotein (P-gp) mediated drug efflux, and pre-systemic metabolism. These all factors cumulatively reduce drug exposure at the target site leading to multidrug resistance (MDR). Lipid based carriers systems has been explored to overcome solubility and permeability related issues of anti-cancer drugs. The lipid based formulations have also been reported to circumvent the effect of P-gp and CYP3A4. Further long chain triglycerides (LCT) has shown their ability to access Lymphatic route over Medium Chain Triglycerides, as the former has been extensively used for targeting anti-cancer drugs at proliferating cells through lymphatic route. Therefore this review tries to reflect the usefulness of lipid based drug carriers systems (viz. liposome, solid lipid nanoparticle, nano-lipid carriers, self-emulsifying, lipidic pro-drugs) in targeting lymphatic system and overcoming issues related to solubility and permeability of anti-cancer drugs. Moreover, we have also tried to reflect how critically lipid based carriers are important in maximizing therapeutic safety and efficacy of anti-cancer drugs.

Highlights

Cancer can be regarded as a multiplex of disease states generated with an outcome of prolonged injuries at tissue and cellular level through interactions with cancer causing agents known as the carcinogens
Further long chain triglycerides (LCT) has shown their ability to access Lymphatic route over Medium Chain Triglycerides, as the former has been extensively used for targeting anti-cancer drugs at proliferating cells through lymphatic route
This review tries to reflect the usefulness of lipid based drug carriers systems in targeting lymphatic system and overcoming issues related to solubility and permeability of anti-cancer drugs

Summary

Introduction

Cancer can be regarded as a multiplex of disease states generated with an outcome of prolonged injuries at tissue and cellular level through interactions with cancer causing agents known as the carcinogens. Recent studies suggested that merely encapsulating the drug into liposomes may sometimes cannot provide sufficient lymphatic targeting, owing to other properties like the particle size, which governs the passage through bio-membranes.[60,61,62] In an another study reported by Hashida et al[63] liposomal formulation of carboxyfluorescein were inefficient in significantly permeating the mucosa of the intestine, but could enter intestinal mucosa when it was co-administered with lipid-surfactant mixed micelles as the latter could interact with intestinal luminal cell membrane, advocating the role of lipid based formulation with concomitant use of surfactants. Findings from Hamishehkar et al[87] were in the agreement that sclareol (poorly water soluble) incorporated SLN was able to exhibit sustained (after 48 hours) and improved antiproliferative activity in A549 cell line

Methodology

Findings

Conclusion and future prospects