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

Abstract

In the treatment of cancer, chemotherapy plays an important role though the efficacy of anticancer 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.

PEGylated SLN as a Promising Approach for Lymphatic Delivery of Gefitinib to Lung Cancer

“… 21 Therefore, the administered drugs are assembled within chylomicron during their production inside enterocytes. 5 …”

“… 5 Therefore, lymphatic drug delivery (LDD) is a promising approach in the treatment of cancer and prevents cancer relapse. 5 …”

“… 4 Orally administered drugs are usually absorbed via the portal vein and exposed to hepatic first-pass metabolism that decreases drug bioavailability. 5 In contrast, the oral dosage forms planned for the LDD could evade hepatic first-pass metabolism and enhance drug bioavailability. 4 In this regard, different types of lipid-based drug delivery systems had been utilized for targeting the LS.…”

“… 4 In this regard, different types of lipid-based drug delivery systems had been utilized for targeting the LS. 5 …”

“…In addition, targeting the LS using the LDD system ensures the elimination of metastatic cancer cells and prevents cancer relapse. 5 …”