Abstract
The lymphatic system (LS) plays a crucial role in fluid balance, transportation of macromolecules,
and immune response. Moreover, LS is a channel for microbial invasion and cancer metastasis.
Particularly, solid tumors, including lung, breast, melanoma, and prostate cancers, are metastasized
across highways of LS. Subsequently, the fabrication of chimeric lymphatic drug delivery systems
(LDDS) is a promising strategy to fight cancer metastasis and control microbial pandemics. In this regard,
LDDS, in terms of PEG-nanoscaled lipid carriers, elicited a revolution during the COVID-19 pandemic
as cargoes for mRNA vaccines. The drug delivered by the lymphatic pathway escapes first-pass
metabolism and enhances the drug's bioavailability. Ample approaches, including synthesis of prodrugs,
trigging of chylomicron biosynthesis, and fabrication of nanocarriers, facilitate lymphatic drug delivery.
Specifically, nanoscales lipid cargoes have the propensity to lymphatic trafficking. Interestingly, TPGSengineered
nanoscale lipid cargoes enhance lymphatic trafficking, increase tissue permeation, and, specifically,
uptake. Moreover, they overcome biological barriers, control biodistribution, and enhance
organelles localization. Most anticancer agents are non-specific, have low bioavailability, and induced
drug resistance. Therefore, TPGS-engineered nanoscale lipid chimeras improve the therapeutic impact
of anticancer agents. This review highlights lymphatic cancer metastasis, nanoscales lipid cargoes as
LDDS, and their influence on lymphatic trafficking, besides the methods of LDD studies.
Graphical Abstract
[20]
Minciacchi, V.R.; Freeman, M.R.; Di Vizio, D. Extracellular vesicles in cancer: Exosomes, microvesicles and the emerging role of large oncosomes. In: Seminars in cell & developmental biology; Elsevier, 2015, pp. 41-51.
[32]
Singh, I.; Swami, R.; Khan, W.; Sistla, R. Lymphatic system: A prospective area for advanced targeting of particulate drug carriers. In: Handbook Of Immunological Properties Of Engineered Nanomaterials 2016, 2, pp. 363-398.
[35]
Chaudhri, V.; Singh, P.; Hussain, Z. Lymphatic system and nanoparticulate carriers for lymphatic delivery. Int J Adv Res Biol Sci, 2016, 3, 142-152.
[51]
Kim, H.; Kim, Y.; Lee, J. Liposomal formulations for enhanced lymphatic drug delivery. Asian J. Pharm., 2013, 8(2), 96-103.
[66]
Quach, T.; Hu, L.; Han, S.; Lim, S.F.; Senyschyn, D.; Yadav, P.; Trevaksis, N.L.; Simpson, J.S.; Porter, C.J. Triglyceride-mimetic prodrugs of buprenorphine enhance oral bioavailability via promotion of lymphatic transport. Front. Pharmacol., 2022, 13, 879660.
[90]
Ghosh, A.; Kaur, C.D.; Gupta, A.; Saraf, S. Surface engineered lamivudine loaded emulsome for targeting drug delivery to lymphatic sys-tem for effective treatment of hiv. Int. J. Appl. Biol. Pharm., 2017, 2(1), 25-37.
[114]
Kumbhar, P.S.; Nadaf, S.; Manjappa, A.S.; Jha, N.K.; Shinde, S.S.; Chopade, S.S.; Shete, A.S.; Disouza, J.I.; Sambamoorthy, U.; Kumar, S.A. D-ɑ-tocopheryl polyethylene glycol succinate: A review of multifarious applications in nanomedicines; OpenNano, 2022, p. 100036.
[124]
Sophie, H. Cardiovascular effects and pattern of use of antineoplastic therapies in female breast cancer patients; Université d'Otta-wa/University of Ottawa, 2014.
[130]
Liu, G.; Lin, Q.; Huang, Y.; Guan, G.; Jiang, Y. Tailoring the particle microstructures of gefitinib by supercritical CO2 anti-solvent process. J. CO2 Util., 2017, 20, 43-51.
[134]
Sherif, Y.A.; Harisa, I.G.; Alanazi, K.F. SLN mediate active delivery of gefitinib into A549 cell line: optimiza-tion, biosafety, and cytotoxi-city studies. Drug Deliv. Lett., 2023, 13, 1-18.