Generic placeholder image

Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Review Article

The Chimera of TPGS and Nanoscale Lipid Carriers as Lymphatic Drug Delivery Vehicles to Fight Metastatic Cancers

Author(s): Abdelrahman Y. Sherif, Gamaleldin I. Harisa* and Fars K. Alanazi

Volume 21, Issue 4, 2024

Published on: 12 June, 2023

Page: [525 - 543] Pages: 19

DOI: 10.2174/1567201820666230512122825

Price: $65


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.

Keywords: Lymphatic drug delivery, nanoscales lipid cargoes, cancer metastasis, TPGS, anticancer agents.

Graphical Abstract
Trevaskis, N.L.; Kaminskas, L.M.; Porter, C.J.H. From sewer to saviour — targeting the lymphatic system to promote drug exposure and activity. Nat. Rev. Drug Discov., 2015, 14(11), 781-803.
[] [PMID: 26471369]
Martin-Almedina, S.; Mortimer, P.S.; Ostergaard, P. Development and physiological functions of the lymphatic system: insights from human genetic studies of primary lymphedema. Physiol. Rev., 2021, 101(4), 1809-1871.
[] [PMID: 33507128]
Managuli, R.S.; Raut, S.Y.; Reddy, M.S.; Mutalik, S. Targeting the intestinal lymphatic system: A versatile path for enhanced oral bioavail-ability of drugs. Expert Opin. Drug Deliv., 2018, 15(8), 787-804.
[] [PMID: 30025212]
Zhang, X-Y.; Lu, W-Y. Recent advances in lymphatic targeted drug delivery system for tumor metastasis. Cancer Biol. Med., 2014, 11(4), 247-254.
[PMID: 25610710]
Clément, O.; Luciani, A. Imaging the lymphatic system: Possibilities and clinical applications. Eur. Radiol., 2004, 14(8), 1498-1507.
[] [PMID: 15007613]
Singh, N.; Handa, M.; Singh, V.; Kesharwani, P.; Shukla, R. Lymphatic targeting for therapeutic application using nanoparticulate systems. J. Drug Target., 2022, 30(10), 1-34.
Hokkanen, K.; Tirronen, A.; Ylä-Herttuala, S. Intestinal lymphatic vessels and their role in chylomicron absorption and lipid homeostasis. Curr. Opin. Lipidol., 2019, 30(5), 370-376.
[] [PMID: 31361624]
Cifarelli, V.; Abumrad, N.A. Enterocyte fatty acid handling proteins and chylomicron formation. In: Physiology of the Gastrointestinal Tract; Elsevier, 2018, pp. 1087-1107.
Yoshida, T.; Kojima, H.; Sako, K.; Kondo, H. Drug delivery to the intestinal lymph by oral formulations. Pharm. Dev. Technol., 2022, 27(2), 175-189.
[] [PMID: 35037843]
Alanazi, S.A.; Alanazi, F.; Haq, N.; Shakeel, F.; Badran, M.M.; Harisa, G.I. Lipoproteins-nanocarriers as a promising approach for target-ing liver cancer: present status and application prospects. Curr. Drug Deliv., 2020, 17(10), 826-844.
[] [PMID: 32026776]
Satapathy, S.; Patro, C.S. Solid lipid nanoparticles for efficient oral delivery of tyrosine kinase inhibitors: A nano targeted cancer drug delivery. Adv. Pharm. Bull., 2022, 12(2), 298-308.
[PMID: 35620346]
Han, S.; Quach, T.; Hu, L.; Wahab, A.; Charman, W.N.; Stella, V.J.; Trevaskis, N.L.; Simpson, J.S.; Porter, C.J.H. Targeted delivery of a model immunomodulator to the lymphatic system: Comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies. J. Control. Release, 2014, 177, 1-10.
[] [PMID: 24398334]
Neupane, A.S.; Kubes, P. Imaging reveals novel innate immune responses in lung, liver, and beyond. Immunol. Rev., 2022, 306(1), 244-257.
[] [PMID: 34816440]
Zhang, Z.; Lu, Y.; Qi, J.; Wu, W. An update on oral drug delivery via intestinal lymphatic transport. Acta Pharm. Sin. B, 2021, 11(8), 2449-2468.
[] [PMID: 34522594]
Ryšánek, P.; Grus, T.; Šíma, M.; Slanař, O. Lymphatic transport of drugs after intestinal absorption: Impact of drug formulation and phys-icochemical properties. Pharm. Res., 2020, 37(9), 166.
[] [PMID: 32770268]
Guan, X. Cancer metastases: Challenges and opportunities. Acta Pharm. Sin. B, 2015, 5(5), 402-418.
[] [PMID: 26579471]
Xu, Y.; Xia, X.; Pan, H. Active autophagy in the tumor microenvironment: A novel mechanism for cancer metastasis. Oncol. Lett., 2013, 5(2), 411-416.
[] [PMID: 23420500]
Leong, S.P.; Zager, J.S. Introduction: Novel frontiers in cancer metastasis. Clin. Exp. Metastasis, 2022, 39(1), 3-5.
[] [PMID: 35192089]
Grüner, B.M.; Fendt, S-M. Cancer cells stock up in lymph vessels to survive; Nature Publishing Group, 2020.
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.
Nicolini, A.; Ferrari, P.; Biava, P.M. Exosomes and cell communication: from tumour-derived exosomes and their role in tumour progres-sion to the use of exosomal cargo for cancer treatment. Cancers, 2021, 13(4), 822.
[] [PMID: 33669294]
Fares, J.; Fares, M.Y.; Khachfe, H.H.; Salhab, H.A.; Fares, Y. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct. Target. Ther., 2020, 5(1), 28.
[] [PMID: 32296047]
Jurj, A.; Zanoaga, O.; Braicu, C.; Lazar, V.; Tomuleasa, C.; Irimie, A.; Berindan-Neagoe, I. A comprehensive picture of extracellular vesi-cles and their contents. Molecular transfer to cancer cells. Cancers, 2020, 12(2), 298.
[] [PMID: 32012717]
Permana, A.D.; Nainu, F.; Moffatt, K.; Larrañeta, E.; Donnelly, R.F. Recent advances in combination of microneedles and nanomedicines for lymphatic targeted drug delivery. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2021, 13(3), e1690.
[] [PMID: 33401339]
Rahman, M.M.; Islam, M.R.; Akash, S.; Harun-Or-Rashid, M.; Ray, T.K.; Rahaman, M.S.; Islam, M.; Anika, F.; Hosain, M.K.; Aovi, F.I.; Hemeg, H.A.; Rauf, A.; Wilairatana, P. Recent advancements of nanoparticles application in cancer and neurodegenerative disorders: At a glance. Biomed. Pharmacother., 2022, 153, 113305.
[] [PMID: 35717779]
Kim, J.; Jozic, A.; Lin, Y.; Eygeris, Y.; Bloom, E.; Tan, X.; Acosta, C.; MacDonald, K.D.; Welsher, K.D.; Sahay, G. Engineering lipid na-noparticles for enhanced intracellular delivery of mrna through inhalation. ACS Nano, 2022, 16(9), 14792-14806.
[] [PMID: 36038136]
Zhang, N-N.; Li, X-F.; Deng, Y-Q.; Zhao, H.; Huang, Y-J.; Yang, G.; Huang, W-J.; Gao, P.; Zhou, C.; Zhang, R-R. A thermostable mRNA vaccine against COVID-19. Cell, 2020, 182(5), 1271-1283.e16.
Koide, H.; Suzuki, H.; Ochiai, H.; Egami, H.; Hamashima, Y.; Oku, N.; Asai, T. Enhancement of target toxin neutralization effect in vivo by PEGylation of multifunctionalized lipid nanoparticles. Biochem. Biophys. Res. Commun., 2021, 555, 32-39.
[] [PMID: 33812056]
Harisa, G.I.; Sherif, A.Y.; Youssof, A.M.E.; Alanazi, F.K.; Salem-Bekhit, M.M. Bacteriosomes as a promising tool in biomedical applica-tions: immunotherapy and drug delivery. AAPS PharmSciTech, 2020, 21(5), 168.
[] [PMID: 32514657]
Vishwakarma, N.; Jain, A.; Sharma, R.; Mody, N.; Vyas, S.; Vyas, S.P. Lipid-based nanocarriers for lymphatic transportation. AAPS PharmSciTech, 2019, 20(2), 83.
[] [PMID: 30673895]
Sensken, S.C.; Bode, C.; Gräler, M.H. Accumulation of fingolimod (FTY720) in lymphoid tissues contributes to prolonged efficacy. J. Pharmacol. Exp. Ther., 2009, 328(3), 963-969.
[] [PMID: 19074680]
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.
Ndayishimiye, J.; Popat, A.; Blaskovich, M.; Falconer, J.R. Formulation technologies and advances for oral delivery of novel nitroimidaz-oles and antimicrobial peptides. J. Control. Release, 2020, 324, 728-749.
[] [PMID: 32380201]
WHO Cancer. 2022. Available from: (Accessed on: 10 01 2022).
Chaudhri, V.; Singh, P.; Hussain, Z. Lymphatic system and nanoparticulate carriers for lymphatic delivery. Int J Adv Res Biol Sci, 2016, 3, 142-152.
Yang, F.; Jin, C.; Yang, D.; Jiang, Y.; Li, J.; Di, Y.; Hu, J.; Wang, C.; Ni, Q.; Fu, D. Magnetic functionalised carbon nanotubes as drug vehi-cles for cancer lymph node metastasis treatment. Eur. J. Cancer, 2011, 47(12), 1873-1882.
[] [PMID: 21493061]
Das, S.S.; Alkahtani, S.; Bharadwaj, P.; Ansari, M.T. ALKahtani, M.D.F.; Pang, Z.; Hasnain, M.S.; Nayak, A.K.; Aminabhavi, T.M. Mo-lecular insights and novel approaches for targeting tumor metastasis. Int. J. Pharm., 2020, 585, 119556.
[] [PMID: 32574684]
Fang, Y.; Wang, H.; Dou, H.J.; Fan, X.; Fei, X.C.; Wang, L.; Cheng, S.; Janin, A.; Wang, L.; Zhao, W.L. Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity. Int. J. Nanomedicine, 2018, 13, 5673-5683.
[] [PMID: 30288040]
Skinner, O.T.; Boston, S.E.; Giglio, R.F.; Whitley, E.M.; Colee, J.C.; Porter, E.G. Diagnostic accuracy of contrast-enhanced computed to-mography for assessment of mandibular and medial retropharyngeal lymph node metastasis in dogs with oral and nasal cancer. Vet. Comp. Oncol., 2018, 16(4), 562-570.
[] [PMID: 29989306]
Patel, P.; Patel, M. Enhanced oral bioavailability of nintedanib esylate with nanostructured lipid carriers by lymphatic targeting: In vitro, cell line and in vivo evaluation. Eur. J. Pharm. Sci., 2021, 159, 105715.
[] [PMID: 33453388]
Yang, H.; Wu, X.; Zhou, Z.; Chen, X.; Kong, M. Enhanced transdermal lymphatic delivery of doxorubicin via hyaluronic acid based trans-fersomes/microneedle complex for tumor metastasis therapy. Int. J. Biol. Macromol., 2019, 125, 9-16.
[] [PMID: 30500513]
Vella, G.; Guelfi, S.; Bergers, G. High endothelial venules: A vascular perspective on tertiary lymphoid structures in cancer. Front. Immunol., 2021, 12, 736670.
[] [PMID: 34484246]
Raza, A.; Rasheed, T.; Nabeel, F.; Hayat, U.; Bilal, M.; Iqbal, H. Endogenous and exogenous stimuli-responsive drug delivery systems for programmed site-specific release. Molecules, 2019, 24(6), 1117.
[] [PMID: 30901827]
Kaminskas, L.M.; McLeod, V.M.; Ascher, D.B.; Ryan, G.M.; Jones, S.; Haynes, J.M.; Trevaskis, N.L.; Chan, L.J.; Sloan, E.K.; Finnin, B.A.; Williamson, M.; Velkov, T.; Williams, E.D.; Kelly, B.D.; Owen, D.J.; Porter, C.J.H. Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats. Mol. Pharm., 2015, 12(2), 432-443.
[] [PMID: 25485615]
Permana, A.D.; Tekko, I.A.; McCrudden, M.T.C.; Anjani, Q.K.; Ramadon, D.; McCarthy, H.O.; Donnelly, R.F. Solid lipid nanoparticle-based dissolving microneedles: A promising intradermal lymph targeting drug delivery system with potential for enhanced treatment of lymphatic filariasis. J. Control. Release, 2019, 316, 34-52.
[] [PMID: 31655132]
Kim, C.K.; Han, J.H. Lymphatic delivery and pharmacokinetics of methotrexate after intramuscular injection of differently charged lipo-some-entrapped methotrexate to rats. J. Microencapsul., 1995, 12(4), 437-446.
[] [PMID: 8583318]
Miao, Y.B.; Lin, Y.J.; Chen, K.H.; Luo, P.K.; Chuang, S.H.; Yu, Y.T.; Tai, H.M.; Chen, C.T.; Lin, K.J.; Sung, H.W. Engineering nano‐ and microparticles as oral delivery vehicles to promote intestinal lymphatic drug transport. Adv. Mater., 2021, 33(51), 2104139.
[] [PMID: 34596293]
Ahn, H.; Park, J.H. Liposomal delivery systems for intestinal lymphatic drug transport. Biomater. Res., 2016, 20(1), 36.
[] [PMID: 27895934]
Caliph, S.M.; Charman, W.N.; Porter, C.J.H. Effect of short-, medium-, and long-chain fatty acid-based vehicles on the absolute oral bioa-vailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph-cannulated and non-cannulated rats. J. Pharm. Sci., 2000, 89(8), 1073-1084.
[<1073:AID-JPS12>3.0.CO;2-V] [PMID: 10906731]
Saha, I.; Rai, V.K. Hyaluronic acid based microneedle array: Recent applications in drug delivery and cosmetology. Carbohydr. Polym., 2021, 267, 118168.
[] [PMID: 34119141]
Kim, H.; Kim, Y.; Lee, J. Liposomal formulations for enhanced lymphatic drug delivery. Asian J. Pharm., 2013, 8(2), 96-103.
Pandya, P.; Giram, P.; Bhole, R.P.; Chang, H.I.; Raut, S.Y. Nanocarriers based oral lymphatic drug targeting: Strategic bioavailability en-hancement approaches. J. Drug Deliv. Sci. Technol., 2021, 64, 102585.
Lin, P.Y.; Chen, K.H.; Miao, Y.B.; Chen, H.L.; Lin, K.J.; Chen, C.T.; Yeh, C.N.; Chang, Y.; Sung, H.W. Phase‐changeable nanoemulsions for oral delivery of a therapeutic peptide: toward targeting the pancreas for antidiabetic treatments using lymphatic transport. Adv. Funct. Mater., 2019, 29(13), 1809015.
Muddineti, O.S.; Ghosh, B.; Biswas, S. Current trends in using polymer coated gold nanoparticles for cancer therapy. Int. J. Pharm., 2015, 484(1-2), 252-267.
[] [PMID: 25701627]
Senthil Kumar, C.; Thangam, R.; Mary, S.A.; Kannan, P.R.; Arun, G.; Madhan, B. Targeted delivery and apoptosis induction of trans-resveratrol-ferulic acid loaded chitosan coated folic acid conjugate solid lipid nanoparticles in colon cancer cells. Carbohydr. Polym., 2020, 231, 115682.
[] [PMID: 31888816]
Nunes, S.; Madureira, A.R.; Campos, D.; Sarmento, B.; Gomes, A.M.; Pintado, M.; Reis, F. Solid lipid nanoparticles as oral delivery sys-tems of phenolic compounds: Overcoming pharmacokinetic limitations for nutraceutical applications. Crit. Rev. Food Sci. Nutr., 2017, 57(9), 1863-1873.
[PMID: 26192708]
Qin, C.; Chu, Y.; Feng, W.; Fromont, C.; He, S.; Ali, J.; Lee, J.B.; Zgair, A.; Berton, M.; Bettonte, S.; Liu, R.; Yang, L.; Monmaturapoj, T.; Medrano-Padial, C.; Ugalde, A.A.R.; Vetrugno, D.; Ee, S.Y.; Sheriston, C.; Wu, Y.; Stocks, M.J.; Fischer, P.M.; Gershkovich, P. Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach. J. Control. Release, 2021, 329, 1077-1089.
[] [PMID: 33091528]
Irby, D.; Du, C.; Li, F. Lipid–drug conjugate for enhancing drug delivery. Mol. Pharm., 2017, 14(5), 1325-1338.
[] [PMID: 28080053]
Ruwizhi, N.; Aderibigbe, B.A. The efficacy of cholesterol-based carriers in drug delivery. Molecules, 2020, 25(18), 4330.
[] [PMID: 32971733]
Alanazi, S.A.; Harisa, G.I.; Badran, M.M.; Alanazi, F.K.; Elzayat, E.; Alomrani, A.H.; Al Meanazel, O.T.; Al Meanazel, A.T. Crosstalk of low density lipoprotein and liposome as a paradigm for targeting of 5-fluorouracil into hepatic cells: Cytotoxicity and liver deposition. Bioengineered, 2021, 12(1), 914-926.
[] [PMID: 33678142]
Wang, X.; Zhang, C.; Han, N.; Luo, J.; Zhang, S.; Wang, C.; Jia, Z.; Du, S. Triglyceride-mimetic prodrugs of scutellarin enhance oral bioa-vailability by promoting intestinal lymphatic transport and avoiding first-pass metabolism. Drug Deliv., 2021, 28(1), 1664-1672.
[] [PMID: 34338567]
Tian, C.; Guo, J.; Miao, Y.; Wang, H.; Ye, Q.; Guo, C.; Zhang, M.; He, Z.; Sun, J. Long chain triglyceride-lipid formulation promotes the oral absorption of the lipidic prodrugs through coincident intestinal behaviors. Eur. J. Pharm. Biopharm., 2022, 176, 122-132.
[] [PMID: 35643367]
Sherif, A.Y.; Harisa, G.I.; Alanazi, F.K.; Nasr, F.A.; Alqahtani, A.S. PEGylated SLN as a promising approach for lymphatic delivery of gefitinib to lung cancer. Int. J. Nanomedicine, 2022, 17, 3287-3311.
[] [PMID: 35924261]
Menard, J.A.; Cerezo-Magaña, M.; Belting, M. Functional role of extracellular vesicles and lipoproteins in the tumour microenvironment. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2018, 373(1737), 20160480.
[] [PMID: 29158310]
Philip, A.; Philip, B. Colon targeted drug delivery systems: A review on primary and novel approaches. Oman Med. J., 2010, 25(2), 70-78.
[] [PMID: 22125706]
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.
Nayek, S.; Raghavendra, N.M.; Sajeev Kumar, B. Development of novel S PC-3 gefitinib lipid nanoparticles for effective drug delivery in breast cancer. Tissue distribution studies and cell cytotoxicity analysis. J. Drug Deliv. Sci. Technol., 2021, 61, 102073.
Zgair, A.; Wong, J.C.; Lee, J.B.; Mistry, J.; Sivak, O.; Wasan, K.M.; Hennig, I.M.; Barrett, D.A.; Constantinescu, C.S.; Fischer, P.M.; Gershkovich, P. Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and canna-bis-based medicines. Am. J. Transl. Res., 2016, 8(8), 3448-3459.
[PMID: 27648135]
Zgair, A.; Lee, J.B.; Wong, J.C.M.; Taha, D.A.; Aram, J.; Di Virgilio, D.; McArthur, J.W.; Cheng, Y.K.; Hennig, I.M.; Barrett, D.A.; Fischer, P.M.; Constantinescu, C.S.; Gershkovich, P. Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intesti-nal lymphatic system and prominent immunomodulation. Sci. Rep., 2017, 7(1), 14542.
[] [PMID: 29109461]
Feng, W.; Qin, C.; Chu, Y.; Berton, M.; Lee, J.B.; Zgair, A.; Bettonte, S.; Stocks, M.J.; Constantinescu, C.S.; Barrett, D.A.; Fischer, P.M.; Gershkovich, P. Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol. Eur. J. Pharm. Biopharm., 2021, 162, 43-49.
[] [PMID: 33677067]
Feng, W.; Qin, C.; Abdelrazig, S.; Bai, Z.; Raji, M.; Darwish, R.; Chu, Y.; Ji, L.; Gray, D.A.; Stocks, M.J.; Constantinescu, C.S.; Barrett, D.A.; Fischer, P.M.; Gershkovich, P. Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol. Int. J. Pharm., 2022, 624, 121947.
[] [PMID: 35753538]
Grove, M.; Müllertz, A.; Nielsen, J.L.; Pedersen, G.P. Bioavailability of seocalcitol. Eur. J. Pharm. Sci., 2006, 28(3), 233-242.
[] [PMID: 16650738]
Sherif, A.Y.; Harisa, G.I.; Alanazi, F.K.; Nasr, F.A.; Alqahtani, A.S. Engineered nanoscale lipid-based formulation as potential enhancer of gefitinib lymphatic delivery: Cytotoxicity and apoptotic studies against the A549 cell line. AAPS PharmSciTech, 2022, 23(6), 183.
[] [PMID: 35773422]
De Oliveira, T.C.; Tavares, M.E.V.; Soares-Sobrinho, J.L.; Chaves, L.L. The role of nanocarriers for transdermal application targeted to lymphatic drug delivery: Opportunities and challenges. J. Drug Deliv. Sci. Technol., 2022, 68, 103110.
Punjabi, M.S.; Naha, A.; Shetty, D.; Nayak, U.Y. Lymphatic drug transport and associated drug delivery technologies: A comprehensive review. Curr. Pharm. Des., 2021, 27(17), 1992-1998.
[] [PMID: 33272166]
Sharma, M.; Gupta, N.; Gupta, S. Implications of designing clarithromycin loaded solid lipid nanoparticles on their pharmacokinetics, antibacterial activity and safety. RSC Advances, 2016, 6(80), 76621-76631.
Shreya, A.B.; Raut, S.Y.; Managuli, R.S.; Udupa, N.; Mutalik, S. Active targeting of drugs and bioactive molecules via oral administration by ligand-conjugated lipidic nanocarriers: recent advances. AAPS PharmSciTech, 2019, 20(1), 15.
[] [PMID: 30564942]
Samad, A.; Sultana, Y.; Aqil, M. Liposomal drug delivery systems: An update review. Curr. Drug Deliv., 2007, 4(4), 297-305.
[] [PMID: 17979650]
Negi, J.S. Nanolipid materials for drug delivery systems: A comprehensive review. In: Characterization and Biology of Nanomaterials for Drug Delivery; 2019, pp. 137-163.
Liu, W.; Ye, A.; Liu, W.; Liu, C.; Han, J.; Singh, H. Behaviour of liposomes loaded with bovine serum albumin during in vitro digestion. Food Chem., 2015, 175, 16-24.
[] [PMID: 25577045]
Kuche, K.; Bhargavi, N.; Dora, C.P.; Jain, S. Drug-phospholipid complex—a go through strategy for enhanced oral bioavailability. AAPS PharmSciTech, 2019, 20(2), 43.
[] [PMID: 30610392]
Liao, H.; Gao, Y.; Lian, C.; Zhang, Y.; Wang, B.; Yang, Y.; Ye, J.; Feng, Y.; Liu, Y. Oral absorption and lymphatic transport of baicalein following drug–phospholipid complex incorporation in self-microemulsifying drug delivery systems. Int. J. Nanomedicine, 2019, 14, 7291-7306.
[] [PMID: 31564878]
Beg, S.; Raza, K.; Kumar, R.; Chadha, R.; Katare, O.P.; Singh, B. Improved intestinal lymphatic drug targeting via phospholipid complex-loaded nanolipospheres of rosuvastatin calcium. RSC Advances, 2016, 6(10), 8173-8187.
Katekar, R.; Sen, S.; Riyazuddin, M.; Husain, A.; Garg, R.; Verma, S.; Mitra, K.; Gayen, J.R. Augmented experimental design for bioavail-ability enhancement: A robust formulation of abiraterone acetate. J. Liposome Res., 2022, 33(4), 1-12.
[] [PMID: 35521749]
Chatterjee, B.; Pandya, M.; Ganti, S. Self-emulsifying drug delivery system for oral anticancer therapy: Constraints and recent develop-ment. Curr. Pharm. Des., 2022, 28(31), 2538-2553.
[] [PMID: 35670356]
Chatterjee, B.; Hamed, A.S.; Ahmed, M.D.A.; Mandal, U.K.; Sengupta, P. Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view. Drug Deliv., 2016, 23(9), 3639-3652.
[] [PMID: 27685505]
Morakul, B. Self-nanoemulsifying drug delivery systems (SNEDDS): An advancement technology for oral drug delivery. Pharm. Sci. Asia, 2020, 47(3), 205-220.
Zembyla, M.; Murray, B.S.; Sarkar, A. Water-in-oil emulsions stabilized by surfactants, biopolymers and/or particles: A review. Trends Food Sci. Technol., 2020, 104, 49-59.
Ye, J.Y.; Chen, Z.Y.; Huang, C.L.; Huang, B.; Zheng, Y.R.; Zhang, Y.F.; Lu, B.Y.; He, L.; Liu, C.S.; Long, X.Y. A non-lipolysis nanoemulsion improved oral bioavailability by reducing the first-pass metabolism of raloxifene, and related absorption mechanisms being studied. Int. J. Nanomedicine, 2020, 15, 6503-6518.
[] [PMID: 32922013]
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.
Elsheikh, M.A.; Rizk, S.A.; Elnaggar, Y.S.R.; Abdallah, O.Y. Nanoemulsomes for enhanced oral bioavailability of the anticancer phyto-chemical andrographolide: Characterization and pharmacokinetics. AAPS PharmSciTech, 2021, 22(7), 246.
[] [PMID: 34617166]
Paliwal, R.; Paliwal, S.R.; Mishra, N.; Mehta, A.; Vyas, S.P. Engineered chylomicron mimicking carrier emulsome for lymph targeted oral delivery of methotrexate. Int. J. Pharm., 2009, 380(1-2), 181-188.
[] [PMID: 19576973]
Baek, J.S.; Cho, C.W. Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake. Eur. J. Pharm. Biopharm., 2017, 117, 132-140.
[] [PMID: 28412471]
Cho, H-J.; Park, J.W.; Yoon, I-S.; Kim, D-D. Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake. Int. J. Nanomedicine, 2014, 9, 495-504.
[PMID: 24531717]
Lin, C-H.; Chen, C-H.; Lin, Z-C.; Fang, J-Y. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers. Yao Wu Shi Pin Fen Xi, 2017, 25(2), 219-234.
[PMID: 28911663]
Chai, G.H.; Xu, Y.; Chen, S.Q.; Cheng, B.; Hu, F.Q.; You, J.; Du, Y.Z.; Yuan, H. Transport mechanisms of solid lipid nanoparticles across Caco-2 cell monolayers and their related cytotoxicology. ACS Appl. Mater. Interfaces, 2016, 8(9), 5929-5940.
[] [PMID: 26860241]
Yu, Z.; Fan, W.; Wang, L.; He, H.; Lv, Y.; Qi, J.; Lu, Y.; Wu, W. Slowing down lipolysis significantly enhances the oral absorption of intact solid lipid nanoparticles. Biomater. Sci., 2019, 7(10), 4273-4282.
[] [PMID: 31407729]
Mahmoudian, M.; Maleki Dizaj, S.; Salatin, S.; Löbenberg, R.; Saadat, M.; Islambulchilar, Z.; Valizadeh, H.; Zakeri-Milani, P. Oral deliv-ery of solid lipid nanoparticles: underlining the physicochemical characteristics and physiological condition affecting the lipolysis rate. Expert Opin. Drug Deliv., 2021, 18(11), 1707-1722.
[] [PMID: 34553650]
Desai, J.; Thakkar, H. Mechanistic evaluation of lymphatic targeting efficiency of Atazanavir sulfate loaded lipid nanocarriers: In-vitro and in-vivo studies. J. Drug Deliv. Sci. Technol., 2022, 68, 103090.
Yu, Z.; Fan, W.; Wang, L.; Qi, J.; Lu, Y.; Wu, W. Effect of surface charges on oral absorption of intact solid lipid nanoparticles. Mol. Pharm., 2019, 16(12), 5013-5024.
[] [PMID: 31638827]
Harisa, G.I.; Sherif, A.Y.; Alanazi, F.K.; Ali, E.A.; Omran, G.A.; Nasr, F.A.; Attia, S.M.; Alqahtani, A.S. TPGS decorated NLC shift ge-fitinib from portal absorption into lymphatic delivery: Intracellular trafficking, biodistribution and bioavailability studies. Colloids Surf. B Biointerfaces, 2023, 223, 113148.
[] [PMID: 36706479]
Shao, Z.; Shao, J.; Tan, B.; Guan, S.; Liu, Z.; Zhao, Z.; He, F.; Zhao, J. Targeted lung cancer therapy: Preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA. Int. J. Nanomedicine, 2015, 10, 1223-1233.
[] [PMID: 25709444]
Ryu, S.; Jin, M.; Lee, H.K.; Wang, M.H.; Baek, J.S.; Cho, C.W. Effects of lipid nanoparticles on physicochemical properties, cellular up-take, and lymphatic uptake of 6-methoxflavone. J. Pharm. Investig., 2022, 52(2), 233-241.
Jannin, V.; Dellera, E.; Chevrier, S.; Chavant, Y.; Voutsinas, C.; Bonferoni, C.; Demarne, F. In vitro lipolysis tests on lipid nanoparticles: comparison between lipase/co-lipase and pancreatic extract. Drug Dev. Ind. Pharm., 2015, 41(10), 1582-1588.
[] [PMID: 25342478]
Brignot, H.; Feron, G. Oral lipolysis and its association with diet and the perception and digestion of lipids: A systematic literature review. Arch. Oral Biol., 2019, 108, 104550.
[] [PMID: 31525532]
Dehaini, D.; Fang, R.H.; Zhang, L. Biomimetic strategies for targeted nanoparticle delivery. Bioeng. Transl. Med., 2016, 1(1), 30-46.
[] [PMID: 29313005]
Sato, Y.T.; Umezaki, K.; Sawada, S.; Mukai, S.; Sasaki, Y.; Harada, N.; Shiku, H.; Akiyoshi, K. Engineering hybrid exosomes by mem-brane fusion with liposomes. Sci. Rep., 2016, 6(1), 21933.
[] [PMID: 26911358]
Sherif, A.Y.; Harisa, G.I.; Alanazi, F.K.; Youssof, A.M.E. Engineering of exosomes: Steps towards green production of drug delivery system. Curr. Drug Targets, 2019, 20(15), 1537-1549.
[] [PMID: 31309889]
Harisa, G.I.; Faris, T.M. Direct drug targeting into intracellular compartments: Issues, limitations, and future outlook. J. Membr. Biol., 2019, 252(6), 527-539.
[] [PMID: 31375855]
Harisa, G.I.; Badran, M.M.; Alanazi, F.K.; Attia, S.M. Crosstalk of nanosystems induced extracellular vesicles as promising tools in bio-medical applications. J. Membr. Biol., 2017, 250(6), 605-616.
[] [PMID: 29127486]
Harisa, G.I.; Badran, M.M.; Alanazi, F.K.; Attia, S.M. An overview of nanosomes delivery mechanisms: Trafficking, orders, barriers and cellular effects. Artif. Cells Nanomed. Biotechnol., 2018, 46(4), 669-679.
[] [PMID: 28701048]
Tavares Luiz, M.; Delello Di Filippo, L.; Carolina Alves, R.; Sousa Araújo, V.H.; Lobato Duarte, J.; Maldonado Marchetti, J.; Chorilli, M. The use of TPGS in drug delivery systems to overcome biological barriers. Eur. Polym. J., 2021, 142, 110129.
Neophytou, C.M.; Constantinou, A.I. Drug delivery innovations for enhancing the anticancer potential of vitamin E isoforms and their derivatives. BioMed Res. Int., 2015, 2015, 584862.
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.
Yang, C.; Wu, T.; Qi, Y.; Zhang, Z. Recent advances in the application of vitamin E TPGS for drug delivery. Theranostics, 2018, 8(2), 464-485.
[] [PMID: 29290821]
Mao, J.; Qiu, L.; Ge, L.; Zhou, J.; Ji, Q.; Yang, Y.; Long, M.; Wang, D.; Teng, L.; Chen, J. Overcoming multidrug resistance by intracellular drug release and inhibiting p-glycoprotein efflux in breast cancer. Biomed. Pharmacother., 2021, 134, 111108.
[] [PMID: 33341670]
Tang, M.; Huang, Y.; Liang, X.; Tao, Y.; He, N.; Li, Z.; Guo, J.; Gui, S. Sorafenib-loaded PLGA-TPGS nanosystems enhance hepatocellu-lar carcinoma therapy through reversing p-glycoprotein-mediated multidrug resistance. AAPS PharmSciTech, 2022, 23(5), 130.
[] [PMID: 35487999]
Hegazy, H.; Amin, M.M.; Fayad, W.; Zakaria, M.Y. TPGS surface modified bilosomes as boosting cytotoxic oral delivery systems of curcumin against doxorubicin resistant MCF-7 breast cancer cells. Int. J. Pharm., 2022, 619, 121717.
[] [PMID: 35378174]
Khutoryanskiy, V.V. Beyond PEGylation: Alternative surface-modification of nanoparticles with mucus-inert biomaterials. Adv. Drug Deliv. Rev., 2018, 124, 140-149.
[] [PMID: 28736302]
Ejigah, V.; Owoseni, O.; Bataille-Backer, P.; Ogundipe, O.D.; Fisusi, F.A.; Adesina, S.K. Approaches to improve macromolecule and na-noparticle accumulation in the tumor microenvironment by the enhanced permeability and retention effect. Polymers, 2022, 14(13), 2601.
[] [PMID: 35808648]
Liu, X.; Zhao, K.; Cao, J.; Qi, X.; Wu, L.; Shen, S. Ultrasound responsive self-assembled micelles loaded with hypocrellin for cancer son-odynamic therapy. Int. J. Pharm., 2021, 608, 121052.
[] [PMID: 34500056]
McCright, J.; Skeen, C.; Yarmovsky, J.; Maisel, K. Nanoparticles with dense poly(ethylene glycol) coatings with near neutral charge are maximally transported across lymphatics and to the lymph nodes. Acta Biomater., 2022, 145, 146-158.
[] [PMID: 35381399]
Zheng, W.; Zhao, Y.; Luo, Q.; Zhang, Y.; Wu, K.; Wang, F. Multi-targeted anticancer agents. Curr. Top. Med. Chem., 2017, 17(28), 3084-3098.
[PMID: 28685693]
Sophie, H. Cardiovascular effects and pattern of use of antineoplastic therapies in female breast cancer patients; Université d'Otta-wa/University of Ottawa, 2014.
Lee, Y.T.; Tan, Y.J.; Oon, C.E. Molecular targeted therapy: Treating cancer with specificity. Eur. J. Pharmacol., 2018, 834, 188-196.
[] [PMID: 30031797]
Ardito, F.; Giuliani, M.; Perrone, D.; Troiano, G.; Muzio, L.L. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy. Review. Int. J. Mol. Med., 2017, 40(2), 271-280.
[] [PMID: 28656226]
Jiao, Q.; Bi, L.; Ren, Y.; Song, S.; Wang, Q.; Wang, Y. Advances in studies of tyrosine kinase inhibitors and their acquired resistance. Mol. Cancer, 2018, 17(1), 36.
[] [PMID: 29455664]
Dar, A.C.; Shokat, K.M. The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling. Annu. Rev. Biochem., 2011, 80(1), 769-795.
[] [PMID: 21548788]
Kim, J.Y.; Kim, H.S.; Yoon, S. Tyrosine kinase inhibitors imatinib and erlotinib increase apoptosis of antimitotic drug-resistant KBV20C cells without inhibiting P-gp. Anticancer Res., 2019, 39(7), 3785-3793.
[] [PMID: 31262905]
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.
Scheffler, M.; Di Gion, P.; Doroshyenko, O.; Wolf, J.; Fuhr, U. Clinical pharmacokinetics of tyrosine kinase inhibitors: focus on 4-anilinoquinazolines. Clin. Pharmacokinet., 2011, 50(6), 371-403.
[] [PMID: 21553932]
Rahman, A.F.M.M.; Korashy, H.M.; Kassem, M.G. Gefitinib. Profiles Drug Subst. Excip. Relat. Methodol., 2014, 39, 239-264.
[] [PMID: 24794908]
Workeneh, B.T.; Uppal, N.N.; Jhaveri, K.D.; Rondon-Berrios, H. Hypomagnesemia in the cancer patient. Kidney360, 2021, 2(1), 154-166.
[] [PMID: 35368816]
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.
Makeen, H.A.; Mohan, S.; Al-Kasim, M.A.; Attafi, I.M.; Ahmed, R.A.; Syed, N.K.; Sultan, M.H.; Al-Bratty, M.; Alhazmi, H.A.; Safhi, M.M.; Ali, R.; Intakhab, A.M. Gefitinib loaded nanostructured lipid carriers: Characterization, evaluation and anti-human colon cancer ac-tivity in vitro. Drug Deliv., 2020, 27(1), 622-631.
[] [PMID: 32329374]
Shao, J.; Xu, Z.; Peng, X.; Chen, M.; Zhu, Y.; Xu, L.; Zhu, H.; Yang, B.; Luo, P.; He, Q. Gefitinib synergizes with irinotecan to suppress hepatocellular carcinoma via antagonizing Rad51-mediated DNA-repair. PLoS One, 2016, 11(1), e0146968.
[] [PMID: 26752698]
Wang, J.; Wang, F.; Li, X.; Zhou, Y.; Wang, H.; Zhang, Y. Uniform carboxymethyl chitosan-enveloped Pluronic F68/poly(lactic-co-glycolic acid) nano-vehicles for facilitated oral delivery of gefitinib, a poorly soluble antitumor compound. Colloids Surf. B Biointerfaces, 2019, 177, 425-432.
[] [PMID: 30798063]
Kobayashi, H.; Sato, K.; Niioka, T.; Miura, H.; Ito, H.; Miura, M. Relationship among gefitinib exposure, polymorphisms of its metaboliz-ing enzymes and transporters, and side effects in Japanese patients with non–small-cell lung cancer. Clin. Lung Cancer, 2015, 16(4), 274-281.
[] [PMID: 25554506]
Sherif, A.Y.; Harisa, G.I.; Shahba, A.A.; Alanazi, F.K.; Qamar, W. Optimization of gefitinib-loaded nanostructured lipid carrier as a bio-medical tool in the treatment of metastatic lung cancer. Molecules, 2023, 28(1), 448.
[] [PMID: 36615641]
Kim, K.S.; Youn, Y.S.; Bae, Y.H. Immune-triggered cancer treatment by intestinal lymphatic delivery of docetaxel-loaded nanoparticle. J. Control. Release, 2019, 311-312, 85-95.
[] [PMID: 31461664]
Chaturvedi, S.; Verma, A.; Saharan, V.A. Lipid drug carriers for cancer therapeutics: An insight into lymphatic targeting, P-gp, CYP3A4 modulation and bioavailability enhancement. Adv. Pharm. Bull., 2020, 10(4), 524-541.
[] [PMID: 33072532]
Zhou, X.; Yung, B.; Huang, Y.; Li, H.; Hu, X.; Xiang, G.; Lee, R.J. Novel liposomal gefitinib (L-GEF) formulations. Anticancer Res., 2012, 32(7), 2919-2923.
[PMID: 22753756]
Lin, Q.; Liu, G.; Zhao, Z.; Wei, D.; Pang, J.; Jiang, Y. Design of gefitinib-loaded poly (l-lactic acid) microspheres via a supercritical anti-solvent process for dry powder inhalation. Int. J. Pharm., 2017, 532(1), 573-580.
[] [PMID: 28935254]
Alshehri, S.; Alanazi, A.; Elzayat, E.M.; Altamimi, M.A.; Imam, S.S.; Hussain, A.; Alqahtani, F.; Shakeel, F. Formulation, in vitro and in vivo evaluation of gefitinib solid dispersions prepared using different techniques. Processes, 2021, 9(7), 1210.
Weber, M.S.; Nicholas, J.A.; Yeaman, M.R. Balancing potential benefits and risks of Bruton Tyrosine Kinase inhibitor therapies in multi-ple sclerosis during the COVID-19 pandemic. Neurol. Neuroimmunol. Neuroinflamm., 2021, 8(6), e1067.
[] [PMID: 34497100]
Morales-Ortega, A.; García de Tena, J.; Frutos-Pérez, B.; Jaenes-Barrios, B.; Farfán-Sedano, A.I.; Canales-Albendea, M.Á.; Bernal-Bello, D. COVID‐19 in patients with hematological malignancies: Considering the role of tyrosine kinase inhibitors. Cancer, 2021, 127(11), 1937-1938.
[] [PMID: 33721325]
Lu, Y.; Qiu, Y.; Qi, J.; Feng, M.; Ju, D.; Wu, W. Biomimetic reassembled chylomicrons as novel association model for the prediction of lymphatic transportation of highly lipophilic drugs via the oral route. Int. J. Pharm., 2015, 483(1-2), 69-76.
[] [PMID: 25681731]
Jewell, A.; Brookes, A.; Feng, W.; Ashford, M.; Gellert, P.; Butler, J.; Fischer, P.M.; Scurr, D.J.; Stocks, M.J.; Gershkovich, P. Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle. Eur. J. Pharm. Biopharm., 2022, 174, 29-34.
[] [PMID: 35364254]
Goo, Y.T.; Sa, C.K.; Kim, M.S.; Sin, G.H.; Kim, C.H.; Kim, H.K.; Kang, M.J.; Lee, S.; Choi, Y.W. Enhanced dissolution and bioavailability of revaprazan using self-nanoemulsifying drug delivery system. Pharm. Dev. Technol., 2022, 27(4), 414-424.
[] [PMID: 35467467]
Gershkovich, P.; Hoffman, A. Uptake of lipophilic drugs by plasma derived isolated chylomicrons: Linear correlation with intestinal lym-phatic bioavailability. Eur. J. Pharm. Sci., 2005, 26(5), 394-404.
[] [PMID: 16140514]
Paliwal, R.; Rai, S.; Vaidya, B.; Khatri, K.; Goyal, A.K.; Mishra, N.; Mehta, A.; Vyas, S.P. Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomedicine, 2009, 5(2), 184-191.
[] [PMID: 19095502]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy