Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Engineered Site-specific Vesicular Systems for Colonic Delivery: Trends and Implications

Author(s): Honey Goel, Karan Razdan, Richu Singla, Sushama Talegaonkar, Rajneet Kaur Khurana, Ashok Kumar Tiwary, Vivek Ranjan Sinha and Kamalinder K. Singh*

Volume 26 , Issue 42 , 2020

Page: [5441 - 5455] Pages: 15

DOI: 10.2174/1381612826666200813132301

Price: $65


Steering drug-loaded, site-specific, coated lipid vesicles to the target receptor sites have the potential of plummeting adverse effects and improving the pharmacological response in diverse pathologies of the large bowel, especially the colon. Colonic delivery via oral route has its own challenges, often governed by several glitches such as drug degradation or absorption in the upper GIT, instability of proteins/peptides due to high molecular weight, and peptidase activity in the stomach. Consequently, colon-specific coated liposomal systems (CSLS) offer a potential alternate for not only site-specificity, but protection from proteolytic activity, and prolonged residence time for greater systemic bioavailability. On the other hand, liposomal delivery via the oral route is also cumbersome owing to several barriers such as instability in GIT, difficulty in crossing membranes, and issues related to production at the pilot scale. New advancements in the field of CSLS have successfully improved the stability and permeability of liposomes for oral delivery via modulating the compositions of lipid bilayers, adding polymers or ligands. Despite this ostensible propitiousness, no commercial oral CSLS has advanced from bench to bedside for targeted delivery to the colon as yet. Nevertheless, CSLS has quite fascinated the manufacturers owing to its potential industrial viability, simplistic and low-cost design. Hence, this review aims to decipher the convolutions involved in the engineering process of industrially viable CSLS for colonic delivery.

Keywords: Coated liposomes, colon drug delivery, colon specific liposomal systems (CSLS), active targeting, immunoliposomes, nanoliposomes, phytochemicals.

Homayun B, Lin X, Choi HJ. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals. Pharmaceutics 2019; 11(3): 129.
[] [PMID: 30893852]
Brown TD, Whitehead KA, Mitragotri S. Materials for oral delivery of proteins and peptides. Nat Rev Mater 2020; 5: 127-48.
O’Driscoll CM, Bernkop-Schnürch A, Friedl JD, Préat V, Jannin V. Oral delivery of non-viral nucleic acid-based therapeutics - do we have the guts for this? Eur J Pharm Sci 2019; 133: 190-204.
[] [PMID: 30946964]
Singhal A, Jain H, Singhal V, Elias EJ, Showkat A. Colon-targeted quercetin delivery using natural polymer to enhance its bioavailability. Pharmacognosy Res 2011; 3(1): 35-9.
[] [PMID: 21731393]
Sinha VR. Honey. Critical aspects in rationale design of fluorouracil-based adjuvant therapies for the management of colon cancer. Crit Rev Ther Drug Carrier Syst 2012; 29(2): 89-148.
[] [PMID: 22577701]
Cao SJ, Xu S, Wang HM, et al. Nanoparticles: Oral delivery for protein and peptide drugs. AAPS PharmSciTech 2019; 20(5): 190.
[] [PMID: 31111296]
Han Y, Gao Z, Chen L, et al. Multifunctional oral delivery systems for enhanced bioavailability of therapeutic peptides/proteins. Acta Pharm Sin B 2019; 9(5): 902-22.
[] [PMID: 31649842]
Bangham AD, Horne RW. Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J Mol Biol 1964; 8: 660-8.
[] [PMID: 14187392]
Bardania H, Tarvirdipour S, Dorkoosh F. Liposome-targeted delivery for highly potent drugs. Artif Cells Nanomed Biotechnol 2017; 45(8): 1478-89.
[] [PMID: 28278584]
He H, Lu Y, Qi J, Zhu Q, Chen Z, Wu W. Adapting liposomes for oral drug delivery. Acta Pharm Sin B 2019; 9(1): 36-48.
[] [PMID: 30766776]
DeSesso JM, Jacobson CF, Williams AL. Anatomical and physiological parameters that influence gastrointestinal absorption. Encyclopedia of Drug Metabolism and Interactions 2012; edsby Alexander V Lyubimov First Edition John Wiley Sons, Inc 2012; 6: 1-34.
Robson AL, Dastoor PC, Flynn J, et al. Advantages and limitations of current imaging techniques for characterizing liposome morphology. Front Pharmacol 2018; 9: 80.
[] [PMID: 29467660]
Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol 2015; 6: 286.
[] [PMID: 26648870]
Guo Y, Zong S, Pu Y, Xu B, Zhang T, Wang B. Advances in pharmaceutical strategies enhancing the efficiencies of oral colon-targeted delivery systems in inflammatory bowel disease. Molecules 2018; 23(7): 1622.
[] [PMID: 29973488]
Tirosh B, Khatib N, Barenholz Y, Nissan A, Rubinstein A. Transferrin as a luminal target for negatively charged liposomes in the inflamed colonic mucosa. Mol Pharm 2009; 6(4): 1083-91.
[] [PMID: 19603812]
Jubeh TT, Barenholz Y, Rubinstein A. Differential adhesion of normal and inflamed rat colonic mucosa by charged liposomes. Pharm Res 2004; 21(3): 447-53.
[] [PMID: 15070095]
Kesisoglou F, Zhou SY, Niemiec S, Lee JW, Zimmermann EM, Fleisher D. Liposomal formulations of inflammatory bowel disease drugs: local versus systemic drug delivery in a rat model. Pharm Res 2005; 22(8): 1320-30.
[] [PMID: 16078142]
Gupta AS, Kshirsagar SJ, Bhalekar MR, Saldanha T. Design and development of liposomes for colon targeted drug delivery. J Drug Target 2013; 21(2): 146-60.
[] [PMID: 23373543]
Alomrani A, Badran M, Harisa GI, et al. The use of chitosan-coated flexible liposomes as a remarkable carrier to enhance the antitumor efficacy of 5-fluorouracil against colorectal cancer. Saudi Pharm J 2019; 27(5): 603-11.
[] [PMID: 31297013]
Lecomte F, Siepmann J, Walther M, MacRae RJ, Bodmeier R. Blends of enteric and GIT-insoluble polymers used for film coating: physicochemical characterization and drug release patterns. J Control Release 2003; 89(3): 457-71.
[] [PMID: 12737848]
Hua S. Orally administered liposomal formulations for colon targeted drug delivery. Front Pharmacol 2014; 5: 138.
[] [PMID: 24959147]
Barea MJ, Jenkins MJ, Lee YS, Johnson P, Bridson RH. Encapsulation of liposomes within pH responsive microspheres for oral colonic drug delivery. Int J Biomater 2012; 2012458712
[] [PMID: 22792110]
Karn PR, Vanić Z, Pepić I, Skalko-Basnet N. Mucoadhesive liposomal delivery systems: the choice of coating material. Drug Dev Ind Pharm 2011; 37(4): 482-8.
[] [PMID: 20961263]
Bansal D, Gulbake A, Tiwari J, Jain SK. Development of liposomes entrapped in alginate beads for the treatment of colorectal cancer. Int J Biol Macromol 2016; 82: 687-95.
[] [PMID: 26464131]
Zhao M, Lee SH, Song JG, Kim HY, Han HK. Enhanced oral absorption of sorafenib via the layer-by-layer deposition of a pH-sensitive polymer and glycol chitosan on the liposome. Int J Pharm 2018; 544(1): 14-20.
[] [PMID: 29655795]
Li D, Nie W, Chen L, et al. The eletrospinning of pH-sensitive 5-FU/RGO composite nanofibers and its potential application for targeted human colon cancer treatment. J Control Release 2017; 59: 23-4.
Ben MS, Marina K, Mukund GS. Eudragit S-100 encapsulated chitosan coated liposomes containing prednisolone for colon targeting: in vitro, ex vivo and in vivo evaluation. J Young Pharm 2019; 11: 7-11.
Jennings JA, Wells CM, McGraw GS, et al. Chitosan coatings to control release and target tissues for therapeutic delivery. Ther Deliv 2015; 6(7): 855-71.
[] [PMID: 26228776]
Lee CM, Kim DW, Lee KY. Effects of chitosan coating for liposomes as an oral carrier. J Exp Biomed Sci 2011; 17: 211-6.
Han HK, Shin HJ, Ha DH. Improved oral bioavailability of alendronate via the mucoadhesive liposomal delivery system. Eur J Pharm Sci 2012; 46(5): 500-7.
[] [PMID: 22522117]
Gradauer K, Barthelmes J, Vonach C, et al. Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats. J Control Release 2013; 172(3): 872-8.
[] [PMID: 24140721]
Gradauer K, Vonach C, Leitinger G, et al. Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties. Int J Nanomedicine 2012; 7: 2523-34.
[PMID: 22679365]
Wu ZH, Ping QN, Lei XM, Li JY, Cai P. Effects of the liposomes coated by chitosan and its derivatives on the gastrointestinal transit of insulin. Yao Xue Xue Bao 2005; 40(7): 618-22.
[PMID: 16196267]
Zariwala MG, Bendre H, Markiv A, et al. Hydrophobically modified chitosan nanoliposomes for intestinal drug delivery. Int J Nanomedicine 2018; 13: 5837-48.
[] [PMID: 30310283]
Chen WL, Yuan ZQ, Liu Y, et al. Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro. Int J Nanomedicine 2016; 11: 325-36.
[PMID: 26855571]
Huang A, Su Z, Li S, et al. Oral absorption enhancement of salmon calcitonin by using both N-trimethyl chitosan chloride and oligoarginines-modified liposomes as the carriers. Drug Deliv 2014; 21(5): 388-96.
[] [PMID: 24188463]
Alshraim MO, Sangi S, Harisa GI, Alomrani AH, Yusuf O, Badran MM. Chitosan-coated flexible liposomes magnify the anticancer activity and bioavailability of docetaxel: Impact on composition. Molecules 2019; 24(2): 250.
[] [PMID: 30641899]
Lara-Espinoza C, Carvajal-Millán E, Balandrán-Quintana R, López-Franco Y, Rascón-Chu A. Pectin and pectin-based composite materials: Beyond food texture. Molecules 2018; 23(4): 942.
[] [PMID: 29670040]
Gawkowska D, Cybulska J, Zdunek A. Structure-related gelling of pectins and linking with other natural compounds: A review. Polymers (Basel) 2018; 10(7): 762.
[] [PMID: 30960687]
Assifaoui A, Loupiac C, Chambin O, Cayot P. Structure of calcium and zinc pectinate films investigated by FTIR spectroscopy. Carbohydr Res 2010; 345(7): 929-33.
[] [PMID: 20303071]
Adkin DA, Kenyon CJ, Lerner EI, et al. The use of scintigraphy to provide “proof of concept” for novel polysaccharide preparations designed for colonic drug delivery. Pharm Res 1997; 14(1): 103-7.
[] [PMID: 9034229]
Li C, Wei YS, Wen P, Feng K, Zong MH, Wu H. Preparation and characterization of an electrospun colon-specific delivery system for salmon calcitonin. RSC Advances 2018; 8: 9762-9.
Feng K, Li C, Wei YS, Zong MH, Wu H, Han SY. Development of a polysaccharide based multi-unit nanofiber mat for colon-targeted sustained release of salmon calcitonin. J Colloid Interface Sci 2019; 552: 186-95.
[] [PMID: 31125829]
Nguyen S, Alund SJ, Hiorth M, Kjøniksen AL, Smistad G. Studies on pectin coating of liposomes for drug delivery. Colloids Surf B Biointerfaces 2011; 88(2): 664-73.
[] [PMID: 21862293]
Negi LM, Jaggi M, Joshi V, Ronodip K, Talegaonkar S. Hyaluronan coated liposomes as the intravenous platform for delivery of imatinib mesylate in MDR colon cancer. Int J Biol Macromol 2015; 73: 222-35.
[] [PMID: 25478964]
Yun Y, Cho YW, Park K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv Drug Deliv Rev 2013; 65(6): 822-32.
[] [PMID: 23123292]
NCT00361842. Multicenter study of CPX-1 (Irinotecan HCl: Floxuridine) liposome injection in patients with advanced colorectal cancer. Available from:
NCT00311610. Liposomal SN-38 in treating patients with metastatic colorectal cancer Available from:
NCT00043199. A safety and effectiveness study of aroplatin in patients with advanced colorectal cancer resistant to standard therapies Available from:
NCT01861496. Phase I/II study to evaluate the safety and tolerability of LiPlaCis in patients with advanced or refractory tumours (LiPlaCis). Available from:
NCT01494506. Study of MM-398 with or without 5-FU/LV, Versus 5-FU/LV in patients with metastatic pancreatic cancer (NAPOLI-1). Available from:
Handali S, Moghimipour E, Rezaei M, et al. A novel 5-Fluorouracil targeted delivery to colon cancer using folic acid conjugated liposomes. Biomed Pharmacother 2018; 108: 1259-73.
[] [PMID: 30372827]
Harel E, Rubinstein A, Nissan A, et al. Enhanced transferrin receptor expression by proinflammatory cytokines in enterocytes as a means for local delivery of drugs to inflamed gut mucosa. PLoS One 2011; 6(9)e24202
[] [PMID: 21915296]
Muzykantov VR. Targeted drug delivery to endothelial adhesion molecules 2013; 1-27.
Mane V, Muro S. Biodistribution and endocytosis of ICAM-1-targeting antibodies versus nanocarriers in the gastrointestinal tract in mice. Int J Nanomedicine 2012; 7: 4223-37.
[PMID: 22915850]
Lombardo D, Kiselev MA, Caccamo MT. Smart nanoparticles for drug delivery application: Development of versatile nanocarrier platforms in biotechnology and nanomedicine. J Nanomater 2019; 20193702518
Ta T, Porter TM. Thermosensitive liposomes for localized delivery and triggered release of chemotherapy. J Control Release 2013; 169(1-2): 112-25.
[] [PMID: 23583706]
de Matos MBC, Beztsinna N, Heyder C, et al. Thermosensitive liposomes for triggered release of cytotoxic proteins. Eur J Pharm Biopharm 2018; 132: 211-21.
[] [PMID: 30223028]
van Elk M, van den Dikkenberg JB, Storm G, Hennink WE, Vermonden T, Heger M. Preclinical evaluation of thermosensitive poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-grafted liposomes for cancer thermochemotherapy. Int J Pharm 2018; 550(1-2): 190-9.
[] [PMID: 30130606]
NCT01464593. Phase 2 study of thermodox as adjuvant therapy with thermal ablation (rfa) in treatment of metastatic colorectal cancer(mCRC) (ABLATE). Available from:
Knights-Mitchell SS, Romanowski M. Near-Infrared activated release of Doxorubicin from plasmon resonant liposomes. Nanotheranostics 2018; 2(4): 295-305.
[] [PMID: 29977741]
Gabizon AA, Patil Y, La-Beck NM. New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy. Drug Resist Updat 2016; 29: 90-106.
[] [PMID: 27912846]
Vail DM, Amantea MA, Colbern GT, Martin FJ, Hilger RA, Working PK. Pegylated liposomal doxorubicin: proof of principle using preclinical animal models and pharmacokinetic studies. Semin Oncol 2004; 31(6)(Suppl. 13): 16-35.
[] [PMID: 15717736]
Lin J, Yu Y, Shigdar S, et al. Enhanced antitumor efficacy and reduced systemic toxicity of sulfatide-containing nanoliposomal doxorubicin in a xenograft model of colorectal cancer. PLoS One 2012; 7(11)e49277
[] [PMID: 23145140]
Xing L, Dawei C, Liping X, Rongqing Z. Oral colon-specific drug delivery for bee venom peptide: development of a coated calcium alginate gel beads-entrapped liposome. J Control Release 2003; 93(3): 293-300.
[] [PMID: 14644579]
Juang V, Chang CH, Wang CS, Wang HE, Lo YL. pH-responsive PEG-shedding and targeting peptide-modified nanoparticles for dual-delivery of irinotecan and microRNA to enhance tumor-specific therapy. Small 2019; 15(49)e1903296
[] [PMID: 31709707]
Shin GH, Chung SK, Kim JT, Joung HJ, Park HJ. Preparation of chitosan-coated nanoliposomes for improving the mucoadhesive property of curcumin using the ethanol injection method. J Agric Food Chem 2013; 61(46): 11119-26.
[] [PMID: 24175657]
De Leo V, Milano F, Mancini E, et al. Encapsulation of curcumin-loaded liposomes for colonic drug delivery in a pH-responsive polymer cluster using a pH-driven and organic solvent-free process. Molecules 2018; 23(4): 739.
[] [PMID: 29570636]
Rollyson WD, Stover CA, Brown KC, et al. Bioavailability of capsaicin and its implications for drug delivery. J Control Release 2014; 196: 96-105.
[] [PMID: 25307998]
Zhu Y, Wang M, Zhang J, et al. Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats. Arch Pharm Res 2015; 38(4): 512-21.
[] [PMID: 25231341]
Terrón-Mejía KA, Martínez-Benavidez E, Higuera-Ciapara I, et al. Mesoscopic modeling of the encapsulation of capsaicin by lecithin/chitosan liposomal nanoparticles. Nanomaterials (Basel) 2018; 8(6): 425.
[] [PMID: 29895747]
Hasan M, Elkhoury K, Kahn CJF, Arab-Tehrany E, Linder M. Preparation, characterization, and release kinetics of chitosan-coated nanoliposomes encapsulating curcumin in simulated environments. Molecules 2019; 24(10): 2023.
[] [PMID: 31137865]
Tian MP, Song RX, Wang T, Sun MJ, Liu Y, Chen XG. Inducing sustained release and improving oral bioavailability of curcumin via chitosan derivatives-coated liposomes. Int J Biol Macromol . 2018; 120(Pt A): 702-10.
[] [PMID: 30170061]
Cuomo F, Cofelice M, Venditti F, et al. In-vitro digestion of curcumin loaded chitosan-coated liposomes. Colloids Surf B Biointerfaces 2018; 168: 29-34.
[] [PMID: 29183647]
Li C, Zhang Y, Su T, Feng L, Long Y, Chen Z. Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin. Int J Nanomedicine 2012; 7: 5995-6002.
[] [PMID: 23233804]
Caddeo C, Gabriele M, Fernàndez-Busquets X, et al. Antioxidant activity of quercetin in Eudragit-coated liposomes for intestinal delivery. Int J Pharm 2019; 565: 64-9.
[] [PMID: 31071415]
Sadeghi Ghadi Z, Dinarvand R, Asemi N, Talebpour Amiri F, Ebrahimnejad P. Preparation, characterization and in vivo evaluation of novel hyaluronan containing niosomes tailored by Box-Behnken design to co-encapsulate curcumin and quercetin. Eur J Pharm Sci 2019; 130: 234-46.
[] [PMID: 30711688]
Nguyen TX, Huang L, Liu L, Elamin Abdalla AM, Gauthier M, Yang G. Chitosan-coated nano-liposomes for the oral delivery of berberine hydrochloride. J Mater Chem B Mater Biol Med 2014; 2(41): 7149-59.
[] [PMID: 32261793]
Giri TK, Dey B, Maity S. Preparation and characterization of nanoemulsome entrapped in enteric coated hydrogel beads for the controlled delivery of Capsaicin to the colon. Curr Drug Ther 2018; 13: 98-105.
Giri TK, Bhowmick S, Maity S. Entrapment of capsaicin loaded nanoliposome in pH responsive hydrogel beads for colonic delivery. J Drug Deliv Sci Technol 2017; 39: 417-22.
Wang M, Zhao T, Liu Y, et al. Ursolic acid liposomes with chitosan modification: Promising antitumor drug delivery and efficacy. Mater Sci Eng C 2017; 71: 1231-40.
[] [PMID: 27987679]
Araki T, Ogawara K, Suzuki H, et al. Augmented EPR effect by photo-triggered tumor vascular treatment improved therapeutic efficacy of liposomal paclitaxel in mice bearing tumors with low permeable vasculature. J Control Release 2015; 200: 106-14.
[] [PMID: 25553829]
Yoshizawa Y, Ogawara K, Kimura T, Higaki K. A novel approach to overcome multidrug resistance: utilization of P-gp mediated efflux of paclitaxel to attack neighboring vascular endothelial cells in tumors. Eur J Pharm Sci 2014; 62: 274-80.
[] [PMID: 24956463]
Mizushina Y, Hada T, Yoshida H. In vivo antitumor effect of liposomes with sialyl Lewis X including monogalactosyl diacylglycerol, a replicative DNA polymerase inhibitor, from spinach. Oncol Rep 2012; 28(3): 821-8.
[] [PMID: 22767329]
Li Y, Zhao H, Duan LR, et al. Preparation, characterization and evaluation of bufalin liposomes coated with citrus pectin. Colloids Surface A 2014; 444: 54-62.
Yuan J, Zeng C, Cao W, et al. Bufalin-loaded pegylated liposomes: antitumor efficacy, acute toxicity, and tissue distribution. Nanoscale Res Lett 2019; 14(1): 223.
[] [PMID: 31278603]
Liposomal doxorubicin market size to reach $139 billion by 2024. Available from:
What it is and how it works. Available from:

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy