Nano lipid based carriers for lymphatic voyage of anti-cancer drugs: An insight into the in-vitro, ex-vivo, in-situ and in-vivo study models

Management of cancer by anti-cancer drugs through conventional approaches has presented tough challenges in clinical settings due to non-selective distribution and low bioavailability of cytotoxic drugs causing serious side-effects and multi drug resistance (MDR). Further, lymph node transmission is regarded as preliminary signs of cancer metastasis. Therefore, lipid based nano-carriers (liposomes, functionalized liposomes, solid lipid nanoparticles, polymer-lipid nanoparticles, nano-lipid carriers, self-micro/nanoemulsifying systems, lipid drug conjugate systems and lipid prodrugs) employing lymphatic voyage offer multitude of advantages like selective targeting to localized as well as metastatic conditions, enhanced bioavailability, controlled delivery and management of MDR conditions. For translational objectives lipid based nano-carriers have been tested on various experimental models, viz. in-vitro lipolysis, in-vitro cell permeation (Cato-2 cell line), in-vitro in-vivo correlations, ex-vivo (everted and non-everted gut sac), in-situ intestinal perfusion, in-vivo (small animals and large animals) and chylomicron flow blocking approach. Therefore, we have summarized for the very first time usefulness of all these models with their characteristics, advantages, shortcomings recent modifications and most importantly their applicability in preclinical and clinical settings for nano-lipid carrier based anti-cancer drug delivery with emphasis on lymphatic targeting. We have also reflected the usefulness of in-silico models as a non-invasive approach to predict lymphatic transport of lipid based nano-carriers. We suggest that successful and rapid clinical translation of lymph targeted nano-lipid carriers in cancer therapy can be attained using these models.