Current NanomedicineCurrent NanomedicineCurrent Nanomedicine2468-18732468-1881Bentham Science67584310.2174/0124681873279965231227051108PharmacologyResearch ArticleBile Acid Nanoparticles - An Emerging Approach for Site Specific Drug TargetingSuvarnaVasantiinfo@benthamscience.netSawantNisergainfo@benthamscience.netJadhavPradnyainfo@benthamscience.netDesaiNamitainfo@benthamscience.netDepartment of Pharmaceutical Chemistry & Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of PharmacyC.U. Shah College of Pharmacy, SNDT Women's University0103202414321222628022025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/2468-1873/article/view/675843

:Bile acids, a group of steroidal acids present in the bile act as biological surfactants and ligands for bile acid transporter proteins for signalling molecules to perform various paracrine and endocrine functions. The enterohepatic circulation of bile acids can be exploited to develop at-tractive drug delivery approaches with improved targetability of facial amphiphiles and enhanced drug bioavailability by improving absorption and metabolic stability. The effectiveness, safety and targetability of nanoparticles conjugated with bile acids and salts have been discussed in the present review. Various modifications of bile acids promoting absorption and oral bioavailability of drugs for treatment of various disease conditions such as cancer, diabetes and psychosis has al-so been discussed. Additionally, neuroprotective effect of bile acids and salts has demonstrated utility in various neurodegenerative disorders. Nanoparticles based on bile acids and salts repre-sent an area of emergent interest due to their unique and modifiable properties for improving ef-fectiveness of drugs.

Bile acidbile saltsnanoparticlesdrug deliverycholic acidchenodeoxycholic acid.Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Arch Intern Med 1999; 159(22): 2647-58. doi: 10.1001/archinte.159.22.2647 PMID: 10597755Li T, Chiang JYL. Regulation of bile acid and cholesterol metabolism by PPARs. PPAR Res 2009; 2009: 1-15. doi: 10.1155/2009/501739 PMID: 19636418Nurunnabi M, Khatun Z, Revuri V, et al. Design and strategies for bile acid mediated therapy and imaging. RSC Advances 2016; 6(78): 73986-4002. doi: 10.1039/C6RA10978KPavlović N, Goločorbin-Kon S, Ðanić M, et al. Bile acids and their derivatives as potential modifiers of drug release and pharmacokinetic profiles. Front Pharmacol 2018; 9: 1283. doi: 10.3389/fphar.2018.01283 PMID: 30467479Lalić-Popović M, Vasović V, Milijašević B, Goločorbin-Kon S, Al-Salami H, Mikov M. Deoxycholic acid as a modifier of the permeation of gliclazide through the blood brain barrier of a rat. J Diabetes Res 2013; 2013: 1-8. doi: 10.1155/2013/598603 PMID: 23671878Moghimipour E, Ameri A, Handali S. Absorption-enhancing effects of bile salts. Molecules 2015; 20(8): 14451-73. doi: 10.3390/molecules200814451 PMID: 26266402Poša M, Guzsvány V, Csanádi J, Kevrešan S, Kuhajda K. Formation of hydrogen-bonded complexes between bile acids and lidocaine in the lidocaine transfer from an aqueous phase to chloroform. Eur J Pharm Sci 2008; 34(4-5): 281-92. doi: 10.1016/j.ejps.2008.04.011 PMID: 18571390Yang L, Tucker IG, Østergaard J. Effects of bile salts on propranolol distribution into liposomes studied by capillary electrophoresis. J Pharm Biomed Anal 2011; 56(3): 553-9. doi: 10.1016/j.jpba.2011.06.020 PMID: 21784594Lee DY, Lee J, Lee S, Kim SK, Byun Y. Liphophilic complexation of heparin based on bile acid for oral delivery. J Control Release 2007; 123(1): 39-45. doi: 10.1016/j.jconrel.2007.07.013 PMID: 17765350Chae HW, Kim IW, Jin HE, Kim DD, Chung SJ, Shim CK. Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine. Arch Pharm Res 2008; 31(1): 103-10. doi: 10.1007/s12272-008-1127-4 PMID: 18277615Davis AP. Cholaphanes et al.; steroids as structural components in molecular engineering. Chem Soc Rev 1993; 22(4): 243. doi: 10.1039/cs9932200243Bhat S, Maitra U. Nanoparticle-gel hybrid material designed with bile acid analogues. Chem Mater 2006; 18(18): 4224-6. doi: 10.1021/cm0607684Pandak WM, Kakiyama G. The acidic pathway of bile acid synthesis: Not just an alternative pathway. Liver Res 2019; 3(2): 88-98. doi: 10.1016/j.livres.2019.05.001 PMID: 32015930Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003; 72(1): 137-74. doi: 10.1146/annurev.biochem.72.121801.161712 PMID: 12543708Kovacevic B, Jones M, Ionescu C, et al. The emerging role of bile acids as critical components in nanotechnology and bioengineering: Pharmacology, formulation optimizers and hydrogel-biomaterial applications. Biomaterials 2022; 283: 121459. doi: 10.1016/j.biomaterials.2022.121459 PMID: 35303546Merkus FWHM, Schipper NGM, Verhoef JC. The influence of absorption enhancers on intranasal insulin absorption in normal and diabetic subjects. J Control Release 1996; 41(1-2): 69-75. doi: 10.1016/0168-3659(96)01357-0Mukhopadhyay S, Maitra U. Chemistry and biology of bile acids. Curr Sci 2004; 87(12): 1666-83.Hofmann AF, Hagey LR. Bile acids: Chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci 2008; 65(16): 2461-83. doi: 10.1007/s00018-008-7568-6 PMID: 18488143Faustino C, Serafim C, Rijo P, Reis CP. Bile acids and bile acid derivatives: Use in drug delivery systems and as therapeutic agents. Expert Opin Drug Deliv 2016; 13(8): 1133-48. doi: 10.1080/17425247.2016.1178233 PMID: 27102882Ackerman HD, Gerhard GS. Bile acids in neurodegenerative disorders. Front Aging Neurosci 2016; 8: 263. doi: 10.3389/fnagi.2016.00263 PMID: 27920719Ridlon JM, Harris SC, Bhowmik S, Kang DJ, Hylemon PB. Consequences of bile salt biotransformations by intestinal bacteria. Gut Microbes 2016; 7(1): 22-39. doi: 10.1080/19490976.2015.1127483 PMID: 26939849Zughaid H, Forbes B, Martin GP, Patel N. Bile salt composition is secondary to bile salt concentration in determining hydrocortisone and progesterone solubility in intestinal mimetic fluids. Int J Pharm 2012; 422(1-2): 295-301. doi: 10.1016/j.ijpharm.2011.11.012 PMID: 22101287Hundt M, Basit H, John S. Physiology, Bile SecretionStatPearls. Treasure Island, FL: StatPearls Publishing 2023.STAMP D, Gareth JSJ. An overview of bile-acid synthesis, chemistry and function. In: Gareth Jenkins, Laura JH, Eds Issues in Toxicology Royal Society of Chemistry. 2008.Patton JS, Carey MC. Inhibition of human pancreatic lipase-colipase activity by mixed bile salt-phospholipid micelles. Am J Physiol 1981; 241(4): G328-36. PMID: 7315970Thomas N, Holm R, Rades T, Müllertz A. Characterising lipid lipolysis and its implication in lipid-based formulation development. AAPS J 2012; 14(4): 860-71. doi: 10.1208/s12248-012-9398-6 PMID: 22956477Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol 2009; 86(3): 215-23. doi: 10.1016/j.yexmp.2008.12.004 PMID: 19186176Song YH, Shin E, Wang H, et al. A novel in situ hydrophobic ion pairing (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system. J Control Release 2016; 229: 106-19. doi: 10.1016/j.jconrel.2016.03.026 PMID: 27001894Allen TM, Cullis PR. Drug delivery systems: Entering the mainstream. Science 2004; 303(5665): 1818-22. doi: 10.1126/science.1095833 PMID: 15031496Ye D, Raghnaill MN, Bramini M, et al. Nanoparticle accumulation and transcytosis in brain endothelial cell layers. Nanoscale 2013; 5(22): 11153-65. doi: 10.1039/c3nr02905k PMID: 24077327He B, Jia Z, Du W, et al. The transport pathways of polymer nanoparticles in MDCK epithelial cells. Biomaterials 2013; 34(17): 4309-26. doi: 10.1016/j.biomaterials.2013.01.100 PMID: 23478037Stern ST, Adiseshaiah PP, Crist RM. Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Part Fibre Toxicol 2012; 9(1): 20. doi: 10.1186/1743-8977-9-20 PMID: 22697169Malhaire H, Gimel JC, Roger E, Benoît JP, Lagarce F. How to design the surface of peptide-loaded nanoparticles for efficient oral bioavailability? Adv Drug Deliv Rev 2016; 106(Pt B): 320-36. doi: 10.1016/j.addr.2016.03.011 PMID: 27058155Moroz E, Matoori S, Leroux JC. Oral delivery of macromolecular drugs: Where we are after almost 100 years of attempts. Adv Drug Deliv Rev 2016; 101: 108-21. doi: 10.1016/j.addr.2016.01.010 PMID: 26826437Maher S, Mrsny RJ, Brayden DJ. Intestinal permeation enhancers for oral peptide delivery. Adv Drug Deliv Rev 2016; 106(Pt B): 277-319. doi: 10.1016/j.addr.2016.06.005 PMID: 27320643Aguirre TAS, Teijeiro-Osorio D, Rosa M, Coulter IS, Alonso MJ, Brayden DJ. Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials. Adv Drug Deliv Rev 2016; 106(Pt B): 223-41. doi: 10.1016/j.addr.2016.02.004 PMID: 26921819Niu Z, Conejos-Sánchez I, Griffin BT, O’Driscoll CM, Alonso MJ. Lipid-based nanocarriers for oral peptide delivery. Adv Drug Deliv Rev 2016; 106(Pt B): 337-54. doi: 10.1016/j.addr.2016.04.001 PMID: 27080735Yun 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. doi: 10.1016/j.addr.2012.10.007 PMID: 23123292Banerjee A, Qi J, Gogoi R, Wong J, Mitragotri S. Role of nanoparticle size, shape and surface chemistry in oral drug delivery. J Control Release 2016; 238: 176-85. doi: 10.1016/j.jconrel.2016.07.051 PMID: 27480450Yu M, Yang Y, Zhu C, Guo S, Gan Y. Advances in the transepithelial transport of nanoparticles. Drug Discov Today 2016; 21(7): 1155-61. doi: 10.1016/j.drudis.2016.05.007 PMID: 27196527Kim K, Kim JH, Kim S, et al. Self-assembled nanoparticles of bile acid-modified glycol chitosans and their applications for cancer therapy. Macromol Res 2005; 13(3): 167-75. doi: 10.1007/BF03219048Winuprasith T, Chantarak S, Suphantharika M, He L, McClements DJ. Alterations in nanoparticle protein corona by biological surfactants: Impact of bile salts on β-lactoglobulin-coated gold nanoparticles. J Colloid Interface Sci 2014; 426: 333-40. doi: 10.1016/j.jcis.2014.04.018 PMID: 24863801Holm R, Müllertz A, Mu H. Bile salts and their importance for drug absorption. Int J Pharm 2013; 453(1): 44-55. doi: 10.1016/j.ijpharm.2013.04.003 PMID: 23598075Mohamed MH, Wang C, Peru KM, Headley JV, Wilson LD. Characterization of the physicochemical properties of β-cyclodextrin-divinyl sulfone polymer carrier-bile acid systems. Mol Pharmaceutics 2017; 14(8): 2616-23.Zhang S, Cui D, Xu J, Wang J, Wei Q, Xiong S. Bile acid transporter mediated STC/Soluplus self-assembled hybrid nanoparticles for enhancing the oral drug bioavailability. Int J Pharm 2020; 579: 119120. doi: 10.1016/j.ijpharm.2020.119120 PMID: 32035254He W, Yang K, Fan L, et al. Denatured globular protein and bile salt-coated nanoparticles for poorly water-soluble drugs: Penetration across the intestinal epithelial barrier into the circulation system and enhanced oral bioavailability. Int J Pharm 2015; 495(1): 9-18. doi: 10.1016/j.ijpharm.2015.08.086 PMID: 26325310Kim DH, Larson AC. Deoxycholate bile acid directed synthesis of branched Au nanostructures for near infrared photothermal ablation. Biomaterials 2015; 56: 154-64. doi: 10.1016/j.biomaterials.2015.03.048 PMID: 25934288Kim D, Yoon J, Kim S, Choi H, Han I, Kim D. A novel transdermal delivery system based on a bile acid-conjugated nanoparticle model for cosmetics. Asian J Beauty Cosmetol 2019; 17(1): 81-91. doi: 10.20402/ajbc.2018.0265Noponen V, Bhat S, Sievänen E, Kolehmainen E. Novel two-step synthesis of gold nanoparticles capped with bile acid conjugates. Mater Sci Eng C 2008; 28(7): 1144-8. doi: 10.1016/j.msec.2007.10.001Mandal RP, Mandal G, Sarkar S, Bhattacharyya A, De S. "Theranostic" role of bile salt-capped silver nanoparticles - gall stone/pigment stone disruption and anticancer activity. J Photochem Photobiol B 2017; 175: 269-81. doi: 10.1016/j.jphotobiol.2017.08.040 PMID: 28923599Matsuoka K, Maeda M, Moroi Y. Micelle formation of sodium glyco- and taurocholates and sodium glyco- and taurodeoxycholates and solubilization of cholesterol into their micelles. Colloids Surf B-Biointerfaces - COLLOID Surf B 2003; 32: 87-95.Kasthuri J, Rajendiran N. Functionalization of silver and gold nanoparticles using amino acid conjugated bile salts with tunable longitudinal plasmon resonance. Colloids Surf B Biointerfaces 2009; 73(2): 387-93. doi: 10.1016/j.colsurfb.2009.06.012 PMID: 19577440Maity M, Sajisha VS, Maitra U. Hydrogelation of bile acid-peptide conjugates and in situ synthesis of silver and gold nanoparticles in the hydrogel matrix. RSC Advances 2015; 5(110): 90712-9. doi: 10.1039/C5RA17917CWong E, Giandomenico CM. Current status of platinum-based antitumor drugs. Chem Rev 1999; 99(9): 2451-66. doi: 10.1021/cr980420v PMID: 11749486Criado JJ, Fernández ER, Manzano JL, et al. Intrinsically fluorescent cytotoxic cisplatin analogues as DNA marker molecules. Bioconjug Chem 2005; 16(2): 275-82. doi: 10.1021/bc049788r PMID: 15769080Guglielmo CD, Lapuente JD, Porredon C, Ramos-López D, Sendra J, Borrás M. in vitro safety toxicology data for evaluation of gold nanoparticles-chronic cytotoxicity, genotoxicity and uptake. J Nanosci Nanotechnol 2012; 12(8): 6185-91. doi: 10.1166/jnn.2012.6430 PMID: 22962725Sánchez-Paradinas S, Pérez-Andrés M, Almendral-Parra MJ, et al. Enhanced cytotoxic activity of bile acid cisplatin derivatives by conjugation with gold nanoparticles. J Inorg Biochem 2014; 131: 8-11. doi: 10.1016/j.jinorgbio.2013.10.021 PMID: 24239907Koyama Y, Ito T, Kimura T, Murakami A, Yamaoka T. Effect of cholesteryl side chain and complexing with cholic acid on gene transfection by cationic poly(ethylene glycol) derivatives. J Control Release 2001; 77(3): 357-64. doi: 10.1016/S0168-3659(01)00521-1 PMID: 11733102Zhu XX, Nichifor M. Polymeric materials containing bile acids. Acc Chem Res 2002; 35(7): 539-46. doi: 10.1021/ar0101180 PMID: 12118993Donvito A, Fantin G, Fogagnolo M, Giovannini PP, Scoponi M. Novel tri- and tetrafunctional cholic acid-based initiators for the synthesis of star-shaped poly(L-lactide)s. Des Monomers Polym 2016; 19(6): 535-44. doi: 10.1080/15685551.2016.1187437Zeng X, Tao W, Mei L, Huang L, Tan C, Feng SS. Cholic acid-functionalized nanoparticles of star-shaped PLGA-vitamin E TPGS copolymer for docetaxel delivery to cervical cancer. Biomaterials 2013; 34(25): 6058-67. doi: 10.1016/j.biomaterials.2013.04.052 PMID: 23694904Wu Y, Wang Z, Liu G, et al. Novel simvastatin-loaded nanoparticles based on cholic acid-core star-shaped PLGA for breast cancer treatment. J Biomed Nanotechnol 2015; 11(7): 1247-60. doi: 10.1166/jbn.2015.2068 PMID: 26307847Jeong JH, Kang SH, Kim DK, Lee NS, Jeong YG, Han SY. Protective effect of cholic acid-coated poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with erythropoietin on experimental stroke. J Nanosci Nanotechnol 2019; 19(10): 6524-33. doi: 10.1166/jnn.2019.17078 PMID: 31026988Yan C, Gu J, Lv Y, Shi W, Huang Z, Liao Y. 5β-cholanic acid/glycol chitosan self-assembled nanoparticles (5β-CHA/GC-NPs) for enhancing the absorption of fds and insulin by rat intestinal membranes. AAPS PharmSciTech 2019; 20(1): 30. doi: 10.1208/s12249-018-1242-6 PMID: 30603934Swaan PW, Szoka FC Jr, Øie S. Use of the intestinal and hepatic bile acid transporters for drug delivery. Adv Drug Deliv Rev 1996; 20(1): 59-82. doi: 10.1016/0169-409X(95)00130-YHo NFH. Utilizing bile acid carrier mechanisms to enhance liver and small intestine absorption. Ann N Y Acad Sci 1987; 507(1): 315-29. doi: 10.1111/j.1749-6632.1987.tb45811.x PMID: 3484365Zhang D, Li D, Shang L, He Z, Sun J. Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption. Int J Pharm 2016; 511(1): 161-9. doi: 10.1016/j.ijpharm.2016.06.139 PMID: 27377011Zhang Z, Li H, Xu G, Yao P. Liver-targeted delivery of insulin-loaded nanoparticles via enterohepatic circulation of bile acids. Drug Deliv 2018; 25(1): 1224-33. doi: 10.1080/10717544.2018.1469685 PMID: 29791242Kim KS, Suzuki K, Cho H, Youn YS, Bae YH. Oral nanoparticles exhibit specific high-efficiency intestinal uptake and lymphatic transport. ACS Nano 2018; 12(9): 8893-900. doi: 10.1021/acsnano.8b04315 PMID: 30088412Kim KS, Suzuki K, Cho H, Bae YH. Selected factors affecting oral bioavailability of nanoparticles surface-conjugated with glycocholic acid via intestinal lymphatic pathway. Mol Pharm 2020; 17(11): 4346-53. doi: 10.1021/acs.molpharmaceut.0c00764 PMID: 33064945Deng F, Kim KS, Moon J, Bae YH. Bile acid conjugation on solid nanoparticles enhances ASBT‐mediated endocytosis and chylomicron pathway but weakens the transcytosis by inducing transport flow in a cellular negative feedback loop. Adv Sci 2022; 9(21): 2201414. doi: 10.1002/advs.202201414 PMID: 35652273Park J, Choi JU, Kim K, Byun Y. Bile acid transporter mediated endocytosis of oral bile acid conjugated nanocomplex. Biomaterials 2017; 147: 145-54. doi: 10.1016/j.biomaterials.2017.09.022 PMID: 28946130Hu Y, He X, Lei L, Liang S, Qiu G, Hu X. Preparation and characterization of self-assembled nanoparticles of the novel carboxymethyl pachyman-deoxycholic acid conjugates. Carbohydr Polym 2008; 74(2): 220-7. doi: 10.1016/j.carbpol.2008.02.014Wu S, Bin W, Tu B, et al. A delivery system for oral administration of proteins/peptides through bile acid transport channels. J Pharm Sci 2019; 108(6): 2143-52. doi: 10.1016/j.xphs.2019.01.027 PMID: 30721709Lee JY, Chung SJ, Cho HJ, Kim DD. Bile acid-conjugated chondroitin sulfate A-based nanoparticles for tumor-targeted anticancer drug delivery. Eur J Pharm Biopharm 2015; 94: 532-41. doi: 10.1016/j.ejpb.2015.06.011 PMID: 26149228Liu M, Du H, Zhai G. Self-assembled nanoparticles based on chondroitin sulfate-deoxycholic acid conjugates for docetaxel delivery: Effect of degree of substitution of deoxycholic acid. Colloids Surf B Biointerfaces 2016; 146: 235-44. doi: 10.1016/j.colsurfb.2016.06.019 PMID: 27343846Park JK, Kim TH, Nam JP, Park SC, Park Y, Jang MK. Bile acid conjugated chitosan oligosaccharide nanoparticles for paclitaxel carrier. Macromol Res 2014; 22(3): 310-7.Fan W, Xia D, Zhu Q, et al. Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery. Biomaterials 2018; 151: 13-23. doi: 10.1016/j.biomaterials.2017.10.022 PMID: 29055774Song Q, Zheng C, Jia J, et al. A probiotic spore‐based oral autonomous nanoparticles generator for cancer therapy. Adv Mater 2019; 31(43): 1903793. doi: 10.1002/adma.201903793 PMID: 31490587Park KB, Jeong YI, Choi KC, Kim SG, Kim HK. Adriamycin-incorporated nanoparticles of deoxycholic acid-conjugated dextran: Antitumor activity against CT26 colon carcinoma. J Nanosci Nanotechnol 2011; 11(5): 4240-9. doi: 10.1166/jnn.2011.3637 PMID: 21780435Chen S, Deng J, Zhang LM. Cationic nanoparticles self-assembled from amphiphilic chitosan derivatives containing poly(amidoamine) dendrons and deoxycholic acid as a vector for co-delivery of doxorubicin and gene. Carbohydr Polym 2021; 258: 117706. doi: 10.1016/j.carbpol.2021.117706 PMID: 33593576Chaturvedi K, Ganguly K, Kulkarni AR, et al. Ultra-small fluorescent bile acid conjugated PHB-PEG block copolymeric nanoparticles: Synthesis, characterization and cellular uptake. RSC Advances 2013; 3(19): 7064-70. doi: 10.1039/c3ra22283gPoupon R. Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: An overview of their mechanisms of action. Clin Res Hepatol Gastroenterol 2012; 36(S1): S3-S12. doi: 10.1016/S2210-7401(12)70015-3 PMID: 23141891Lee HM, Jeong YI, Kim DH, et al. Ursodeoxycholic acid-conjugated chitosan for photodynamic treatment of HuCC-T1 human cholangiocarcinoma cells. Int J Pharm 2013; 454(1): 74-81. doi: 10.1016/j.ijpharm.2013.06.035 PMID: 23834828De AK, Sana S, Datta S, Mukherjee A. Protective efficacy of ursodeoxycholic acid nanoparticles in animal model of inflammatory bowel disease. J Microencapsul 2014; 31(8): 725-37. doi: 10.3109/02652048.2014.918666 PMID: 24963957Dalpiaz A, Contado C, Mari L, et al. Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid. Drug Deliv 2014; 21(3): 221-32. doi: 10.3109/10717544.2013.844744 PMID: 24134683Enhsen A, Kramer W, Wess G. Bile acids in drug discovery. Drug Discov Today 1998; 3(9): 409-18. doi: 10.1016/S1359-6446(96)10046-5Simental-Mendía LE, Simental-Mendía M, Sánchez-García A, et al. Impact of ursodeoxycholic acid on circulating lipid concentrations: A systematic review and meta-analysis of randomized placebo-controlled trials. Lipids Health Dis 2019; 18(1): 88. doi: 10.1186/s12944-019-1041-4 PMID: 30954082Khatun Z, Nurunnabi M, Reeck GR, Cho KJ, Lee Y. Oral delivery of taurocholic acid linked heparin-docetaxel conjugates for cancer therapy. J Control Release 2013; 170(1): 74-82. doi: 10.1016/j.jconrel.2013.04.024 PMID: 23665255Tian C, Asghar S, Wu Y, et al. Improving intestinal absorption and oral bioavailability of curcumin via taurocholic acid-modified nanostructured lipid carriers. Int J Nanomedicine 2017; 12: 7897-911. doi: 10.2147/IJN.S145988 PMID: 29138557Chaturvedi K, Ganguly K, Kulkarni AR, et al. Oral insulin delivery using deoxycholic acid conjugated PEGylated polyhydroxybutyrate co-polymeric nanoparticles. Nanomedicine 2015; 10(10): 1569-83. doi: 10.2217/nnm.15.36 PMID: 26008194Khatun Z, Nurunnabi M, Cho KJ, Lee Y. Imaging of the GI tract by QDs loaded heparin-deoxycholic acid (DOCA) nanoparticles. Carbohydr Polym 2012; 90(4): 1461-8. doi: 10.1016/j.carbpol.2012.07.016 PMID: 22944403Gao F, Li L, Zhang H, et al. Deoxycholic acid modified-carboxymethyl curdlan conjugate as a novel carrier of epirubicin: In vitro and in vivo studies. Int J Pharm 2010; 392(1-2): 254-60. doi: 10.1016/j.ijpharm.2010.03.044 PMID: 20347028Chae SY, Son S, Lee M, Jang MK, Nah JW. Deoxycholic acid-conjugated chitosan oligosaccharide nanoparticles for efficient gene carrier. J Control Release 2005; 109(1-3): 330-44. doi: 10.1016/j.jconrel.2005.09.040 PMID: 16271416Han Y, Liu W, Chen L, et al. Effective oral delivery of Exenatide-Zn2+ complex through distal ileum-targeted double layers nanocarriers modified with deoxycholic acid and glycocholic acid in diabetes therapy. Biomaterials 2021; 275: 120944. doi: 10.1016/j.biomaterials.2021.120944 PMID: 34153783Wang T, Wang F, Sun M, et al. Gastric environment-stable oral nanocarriers for in situ colorectal cancer therapy. Int J Biol Macromol 2019; 139: 1035-45. doi: 10.1016/j.ijbiomac.2019.08.088 PMID: 31412265Lee JY, Lee SH, Oh MH, Kim JS, Park TG, Nam YS. Prolonged gene silencing by siRNA/chitosan-g-deoxycholic acid polyplexes loaded within biodegradable polymer nanoparticles. J Control Release 2012; 162(2): 407-13. doi: 10.1016/j.jconrel.2012.07.006 PMID: 22800573Armin M, Nassim Z, Ryu T, et al. Probucol-poly(meth)acrylate-bile acid nanoparticles increase IL-10, and primary bile acids in prediabetic mice. Ther Deliv 2019; 10(9): 563-71.Arai Y, Park H, Park S, et al. Bile acid-based dual-functional prodrug nanoparticles for bone regeneration through hydrogen peroxide scavenging and osteogenic differentiation of mesenchymal stem cells. J Control Release 2020; 328: 596-607. doi: 10.1016/j.jconrel.2020.09.023 PMID: 32946872Nandini P, Doijad R, Dandagi HNSP. Formulation and evaluation of gemcitabine-loaded solid lipid nanoparticles. Drug Deliv 2013; 22(5): 647-51.Jha SK, Chung JY, Pangeni R, et al. Enhanced antitumor efficacy of bile acid-lipid complex-anchored docetaxel nanoemulsion via oral metronomic scheduling. J Control Release 2020; 328: 368-94. doi: 10.1016/j.jconrel.2020.08.067 PMID: 32890552Fahmy TM, Lee JS, Kim D. Polymeric bile acid ester nanoparticles comprising an immunomodulator agent to induce antigen-specific tolerance. WO Patent 2021258042, 2021.Fahmy TM. Polymeric bile acid nanocompositions targeting the pancreas and colon. EP Patent 3347794A1, 2018.Nah JW, Jung TR, Chae SY, Jang MK, Choi CY. Anti-cancer agent loaded hydrophobic bile acid conjugated hydrophilic chitosan oligosaccharide nanoparticles and preparation method thereof. WO Patent 2007086651, 2007.Lee KC, Chae SY, Shin JH. Exendin-4 derivative linked hydrophobic bile acid, method for the preparation thereof and pharmaceutical composition comprising the same. KR Patent 100746658, 2007.Lee YK, Lee DY, Kang SH. Orally administered nanoparticles for gene delivery and pharmaceutical composition containing same. EP Patent 3449944A1, 2019.Perez MJ, Briz O. Bile-acid-induced cell injury and protection. World J Gastroenterol 2009; 15(14): 1677-89. doi: 10.3748/wjg.15.1677 PMID: 19360911Bernstein C, Holubec H, Bhattacharyya AK, et al. Carcinogenicity of deoxycholate, a secondary bile acid. Arch Toxicol 2011; 85(8): 863-71. doi: 10.1007/s00204-011-0648-7 PMID: 21267546Ðanić M, Stanimirov B, Pavlović N, et al. Pharmacological applications of bile acids and their derivatives in the treatment of metabolic syndrome. Front Pharmacol 2018; 9: 1382. doi: 10.3389/fphar.2018.01382 PMID: 30559664Chen G, Yang L, Zhang H, Tucker IG, Fawcett JP. Effect of ketocholate derivatives on methotrexate uptake in Caco-2 cell monolayers. Int J Pharm 2012; 433(1-2): 89-93. doi: 10.1016/j.ijpharm.2012.04.077 PMID: 22575673