Bile acid/fatty acid integrated nanoemulsomes for nonalcoholic fatty liver targeted lovastatin delivery: stability, in-vitro, ex-vivo, and in-vivo analyses

References

• Chen Z, Qin H, Qiu S, et al. Correlation of triglyceride to high-density lipoprotein cholesterol ratio with nonalcoholic fatty liver disease among the non-obese Chinese population with normal blood lipid levels: a retrospective cohort research. Lipids Health Dis. 2019;18(1):1–7. doi: 10.1186/s12944-019-1104-6
   PubMed Web of Science ®Google Scholar
• Khan MA, Hashim, M.J., Mustafa, H et al. Global epidemiology of ischemic heart disease: results from the global burden of disease study. Cureus. 2020:12(7). doi: 10.7759/cureus.9349
   Web of Science ®Google Scholar
• Geng Y, Faber KN, de Meijer VE, et al. How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease? Hepatol Int. 2021;15(1):21–35. doi: 10.1007/s12072-020-10121-2
   PubMed Web of Science ®Google Scholar
• Bence KK, Birnbaum MJ. Metabolic drivers of non-alcoholic fatty liver disease. Mol Metabol. 2021;50:101143. doi: 10.1016/j.molmet.2020.101143
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Marchesini G, Pinto-Cortez H, et al. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: implications for liver transplantation. Transplantation. 2019;103(1):22–27. doi: 10.1097/TP.0000000000002484
   PubMed Web of Science ®Google Scholar
• Murag S, Ahmed A, Kim D. Recent epidemiology of nonalcoholic fatty liver disease. Gut Liver. 2021;15(2):206. doi: 10.5009/gnl20127
   PubMed Web of Science ®Google Scholar
• Jarvis H, Craig D, Barker R, et al. Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of population-based observational studies. PLOS Med. 2020;17(4):e1003100. doi: 10.1371/journal.pmed.1003100
   PubMed Web of Science ®Google Scholar
• Kothari S, Dhami-Shah H, Shah SR. Antidiabetic drugs and statins in nonalcoholic fatty liver disease. J Clin Exp Hepatol. 2019;9(6):723–730. doi: 10.1016/j.jceh.2019.06.003
   PubMed Web of Science ®Google Scholar
• Newsome JS. Evaluation of statin treatment for nonalcoholic fatty liver disease. J Pharm Technol. 2016;32(4):169–173. doi: 10.1177/8755122516640800
   Google Scholar
• Stone NJ, Robinson JG, Lichtenstein AH, et al. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: synopsis of the 2013 American college of cardiology/American heart association cholesterol guideline. Ann Internal Med. 2014;160(5):339–343. doi: 10.7326/M14-0126
   PubMed Web of Science ®Google Scholar
• Nazarov FY, Makhmudova KD. The use of statins and drugs that inhibit the absorption of cholesterol in patients with coronary heart disease. GIIRJ. 2022;10(1):306–309.
   Google Scholar
• Cicero AF, Fogacci F, Zambon A. Red yeast rice for hypercholesterolemia: JACC focus seminar. J Am Coll Cardiol. 2021;77(5):620–628. doi: 10.1016/j.jacc.2020.11.056
   PubMed Web of Science ®Google Scholar
• Tobert J, Hitzenberger G, Kukovetz WR, et al. Rapid and substantial lowering of human serum cholesterol by mevinolin (MK-803), an inhibitor of hydroxymethylglutaryl-coenzyme a reductase. Atherosclerosis. 1982;41(1):61–65. doi: 10.1016/0021-9150(82)90070-3
   PubMed Web of Science ®Google Scholar
• Duong H, Bajaj T. Lovastatin. 2019.
   Google Scholar
• UmakantVerma J, Mokale V. Preparation of freeze-dried solid dispersion powder using mannitol to enhance solubility of lovastatin and development of sustained release tablet dosage form. Am IJPSN. 2014;1(1):11–26.
   Google Scholar
• Gaber DA. Nanoparticles of lovastatin: design, optimization and in vivo evaluation. Int J Nanomed. 2020:15:4225–4236. doi: 10.2147/IJN.S241120
   Google Scholar
• Sarkar MR, Sikdar KY, Monjur-Al-Hossain AS, et al. Improving the drug dissolution profile of poorly aqueous soluble lovastatin using hydrophilic polymers by solid dispersion and physical mixing techniques. Natl J Physiol Pharm Pharmacol. 2021;11(2):216–216. doi: 10.5455/njppp.2021.11.12347202022122020
   Google Scholar
• Kajdič S, Zupančič Š, Roškar R, et al. The potential of nanofibers to increase solubility and dissolution rate of the poorly soluble and chemically unstable drug lovastatin. Int J Pharmaceut. 2020;573:118809. doi: 10.1016/j.ijpharm.2019.118809
   PubMed Web of Science ®Google Scholar
• Mahmood A, Sharif A, Muhammad F, et al. Development and in vitro evaluation of (β-cyclodextrin-g-methacrylic acid)/Na+-montmorillonite nanocomposite hydrogels for controlled delivery of lovastatin. IJN. 2019;14:5397–5413. doi: 10.2147/IJN.S209662
   Google Scholar
• Abu Mellal A, Hussain N, Said AS. The clinical significance of statins-macrolides interaction: comprehensive review of in vivo studies, case reports, and population studies. TCRM. 2019;15:921–936. doi: 10.2147/TCRM.S214938
   Google Scholar
• Elsheikh MA, Rizk SA, Elnaggar YSR, et al. Nanoemulsomes for enhanced oral bioavailability of the anticancer phytochemical andrographolide: characterization and pharmacokinetics. AAPS Pharm Sci Tech. 2021;22(7):1–12. doi: 10.1208/s12249-021-02112-9
   Web of Science ®Google Scholar
• Panyod S, Sheen L-Y. Beneficial effects of Chinese herbs in the treatment of fatty liver diseases. J Tradit Complement Med. 2020;10(3):260–267. doi: 10.1016/j.jtcme.2020.02.008
   PubMedGoogle Scholar
• Kumar Gupta S, Sharma AJJOP, Sciences B. Medicinal properties Of Zingiber officinale roscoe-a review. IOSR J Pharm Bio Sci. 2014;9(5):124–129. doi: 10.9790/3008-0955124129
   Google Scholar
• Afshari AT, Shirpoor A, Farshid A, et al. The effect of ginger on diabetic nephropathy, plasma antioxidant capacity and lipid peroxidation in rats. Food Chem. 2007;101(1):148–153. doi: 10.1016/j.foodchem.2006.01.013
   Web of Science ®Google Scholar
• Abdel-Azeem AS, Hegazy AM, Ibrahim KS, et al. Hepatoprotective, antioxidant, and ameliorative effects of ginger (Zingiber officinale Roscoe) and vitamin E in acetaminophen treated rats. J Diet Suppl. 2013;10(3):195–209. doi: 10.3109/19390211.2013.822450
   PubMedGoogle Scholar
• Akhani SP, Vishwakarma SL, Goyal RK. Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats. J Pharm Pharmacol. 2004;56(1):101–105. doi: 10.1211/0022357022403
   PubMed Web of Science ®Google Scholar
• ElRokh E-SM, Yassin NAZ, El-Shenawy SMA, et al. Antihypercholesterolaemic effect of ginger rhizome (Zingiber officinale) in rats. Inflammopharmacology. 2010;18(6):309–315. doi: 10.1007/s10787-010-0053-5
   PubMedGoogle Scholar
• Yu L, Zhao R, Wang C, et al. Effects of garlic supplementation on non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials. J Funct Foods. 2022;99:105294. doi: 10.1016/j.jff.2022.105294
   Web of Science ®Google Scholar
• Katopodi A, Detsi A. Solid lipid nanoparticles and nanostructured lipid carriers of natural products as promising systems for their bioactivity enhancement: the case of essential oils and flavonoids. Colloids Surf A Physicochem Eng Asp. 2021;630:127529. doi: 10.1016/j.colsurfa.2021.127529
   Web of Science ®Google Scholar
• Nemati M, Fathi‐Azarbayjani A, Al‐Salami H, et al. Bile acid‐based advanced drug delivery systems, bilosomes and micelles as novel carriers for therapeutics. Cell Biochem Funct. 2022;40(6):623–635. doi: 10.1002/cbf.3732
   PubMed Web of Science ®Google Scholar
• Chen W, Feng Z, Sun Q. A novel ursodeoxycholic acid–chitosan-folate conjugates for the delivery of calcitriol for cancer therapy. J Drug Delivery Sci Technol. 2022;73:103410. doi: 10.1016/j.jddst.2022.103410
   Web of Science ®Google Scholar
• Zhou T, Liu Y, Lei K, et al. A “Trojan Horse” Strategy: The Preparation of Bile Acid-Modifying Irinotecan Hydrochloride Nanoliposomes for Liver-Targeted Anticancer Drug Delivery System Study. Molecules. 2023;28(4):1577. doi: 10.3390/molecules28041577
   PubMed Web of Science ®Google Scholar
• Arab JP, Arrese M, Shah VH. Gut microbiota in non‐alcoholic fatty liver disease and alcohol‐related liver disease: Current concepts and perspectives. Hepatol Res. 2020;50(4):407–418. doi: 10.1111/hepr.13473
   PubMed Web of Science ®Google Scholar
• Cheong S-J, Lee C-M, Kim S-L, et al. Superparamagnetic iron oxide nanoparticles-loaded chitosan-linoleic acid nanoparticles as an effective hepatocyte-targeted gene delivery system. Int J Pharmaceut. 2009;372(1–2):169–176. doi: 10.1016/j.ijpharm.2009.01.009
   PubMed Web of Science ®Google Scholar
• O’Reilly ME, Lenighan YM, Dillon E, et al. Conjugated linoleic acid and alpha linolenic acid improve cholesterol homeostasis in obesity by modulating distinct hepatic protein pathways. Molecular nutrition food research. Mol Nutr Food Res. 2020;64(7):1900599. doi: 10.1002/mnfr.201900599
   Web of Science ®Google Scholar
• Bakhle SS. Development and evaluation of liquid and solid self-microemulsifying drug delivery system of lovastatin. Asian J Pharm (AJP). 2016:10(1). doi: 10.22377/ajp.v10i1
   Google Scholar
• Conacher M, Alexander J, Brewer JM. Oral immunisation with peptide and protein antigens by formulation in lipid vesicles incorporating bile salts (bilosomes). Vaccine. 2001;19(20–22):2965–2974. doi: 10.1016/S0264-410X(00)00537-5
   PubMed Web of Science ®Google Scholar
• Rizk SA, Elsheikh MA, R Elnaggar YS, et al. Novel bioemulsomes for baicalin oral lymphatic targeting: development, optimization and pharmacokinetics. Nanomedicine (Lond). 2021;16(22):1983–1998. doi: 10.2217/nnm-2021-0137
   PubMed Web of Science ®Google Scholar
• Kadian V, Dalal P, Kumar S, et al. Comparative evaluation of dithranol-loaded nanosponges fabricated by solvent evaporation technique and melt method. Future J Pharm Sci. 2023;9(1):1–15. doi: 10.1186/s43094-023-00461-9
   PubMed Web of Science ®Google Scholar
• Aldawsari HM, Badr-Eldin SM, Assiri NY, et al. Surface-tailoring of emulsomes for boosting brain delivery of vinpocetine via intranasal route: in vitro optimization and in vivo pharmacokinetic assessment. Drug Delivery. 2022;29(1):2671–2684. doi: 10.1080/10717544.2022.2110996
   PubMed Web of Science ®Google Scholar
• Overhoff KA, Moreno A, Miller DA, et al. Solid dispersions of itraconazole and enteric polymers made by ultra-rapid freezing. Int J Pharmaceut. 2007;336(1):122–132. doi: 10.1016/j.ijpharm.2006.11.043
   PubMed Web of Science ®Google Scholar
• Li S-W, Song H-P, Leng Y. Rapid determination of lovastatin in the fermentation broth of Aspergillus terreus using dual-wavelength UV spectrophotometry. Pharm Biol. 2014;52(1):129–135. doi: 10.3109/13880209.2013.833947
   PubMed Web of Science ®Google Scholar
• Langert KA, Goshu B, Stubbs Jr EB. Attenuation of experimental autoimmune neuritis with locally administered lovastatin‐encapsulating poly (lactic‐co‐glycolic) acid nanoparticles. J Neurochem. 2017;140(2):334–346. doi: 10.1111/jnc.13892
   PubMed Web of Science ®Google Scholar
• Ismail NS. Protective effects of aqueous extracts of cinnamon and ginger herbs against obesity and diabetes in obese diabetic rat. World J Dairy Food Sci. 2014;9(2):145–153.
   Google Scholar
• Chien M-Y, Ku Y-H, Chang J-M, et al. Effects of herbal mixture extracts on obesity in rats fed a high-fat diet. J Food Drug Anal. 2016;24(3):594–601. doi: 10.1016/j.jfda.2016.01.012
   PubMed Web of Science ®Google Scholar
• Shaikh AS, Thomas AB, Chitlange SS. Herb–drug interaction studies of herbs used in treatment of cardiovascular disorders—a narrative review of preclinical and clinical studies. Phytother Res. 2020;34(5):1008–1026. doi: 10.1002/ptr.6585
   PubMed Web of Science ®Google Scholar
• Ahmed T. High dose Simvastatin as a potential anticancer therapy in leukemia patients. 2013.
   Google Scholar
• Shukr MH, Ismail S, Ahmed SM. Development and optimization of ezetimibe nanoparticles with improved antihyperlipidemic activity. J Drug Delivery Sci Technol. 2019;49:383–395. doi: 10.1016/j.jddst.2018.12.001
   Web of Science ®Google Scholar
• Babic N, Valjevac A, Zaciragic A, et al. The triglyceride/HDL ratio and triglyceride glucose index as predictors of glycemic control in patients with diabetes mellitus type 2. Med Arch. 2019;73(3):163. doi: 10.5455/medarh.2019.73.163-168
   PubMedGoogle Scholar
• Lai YS, Lee W-C, Lin Y-E, et al. Ginger essential oil ameliorates hepatic injury and lipid accumulation in high fat diet-induced nonalcoholic fatty liver disease. J Agric Food Chem. 2016;64(10):2062–2071. doi: 10.1021/acs.jafc.5b06159
   PubMed Web of Science ®Google Scholar
• Singh V, Pandey H, Misra V, et al. Hypolipidemic effect of [6]-Gingerol-loaded Eudragit polymeric nanoparticles in high-fat diet-induced rats and gamma scintigraphy evaluation of gastric-retention time. J Appl Pharm Sci. 2022;12(6):156–163. doi: 10.7324/JAPS.2022.120615
   Google Scholar
• Abbas H, El Sayed NS, Ali ME, et al. Integrated lecithin–bile salt nanovesicles as a promising approach for effective skin delivery of luteolin to improve UV-induced skin damage in Wistar albino rats. Colloids Surf B Biointerfaces. 2022;211:112299. doi: 10.1016/j.colsurfb.2021.112299
   PubMed Web of Science ®Google Scholar
• Cordenonsi LM, Santer A, Sponchiado RM, et al. Amazonia products in novel lipid nanoparticles for fucoxanthin encapsulation. AAPS Pharm Sci Tech. 2020;21(1):1–10. doi: 10.1208/s12249-019-1601-y
   Web of Science ®Google Scholar
• Afreen U, Hussain Shah SN, Aslam R, et al. Synthesis and in vitro characterization of chlorpheneramine-laden liposomes for topical applications. Pak J Pharm Sci. 2021;34(5):1767–1776.
   PubMed Web of Science ®Google Scholar
• Mallick A, Sahu R, Nandi G, et al. Development of liposomal formulation for controlled delivery of valacyclovir: an in vitro study. J Pharm Innov. 2023;18(3):1020–1029.
   Web of Science ®Google Scholar
• Behiry EG, El Nady NM, AbdEl Haie OM, et al. Evaluation of TG-HDL ratio instead of HOMA ratio as insulin resistance marker in overweight and children with obesity. endocrine, metabolic & immune disorders-drug targets (formerly current drug targets-immune. Endocr Met Dis. 2019;19(5):676–682. doi: 10.2174/1871530319666190121123535
   Google Scholar
• Yang Y, Chen J, Gao Q, et al. Study on the attenuated effect of Ginkgolide B on ferroptosis in high fat diet induced nonalcoholic fatty liver disease. Toxicology. 2020;445:152599. doi: 10.1016/j.tox.2020.152599
   PubMed Web of Science ®Google Scholar
• Zhong L, Lyu W, Lin Z, et al. Quinoa ameliorates hepatic steatosis, oxidative stress, inflammation and regulates the gut microbiota in nonalcoholic fatty liver disease rats. Foods. 2023;12(9):1780. doi: 10.3390/foods12091780
   PubMed Web of Science ®Google Scholar
• Meng F, Asghar S, Gao S, et al. A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer’s disease. Colloids Surf B. 2015;134:88–97. doi: 10.1016/j.colsurfb.2015.06.025
   PubMed Web of Science ®Google Scholar
• Argo B, Hermanto MB, Andriani DW, et al. The effect of ginger oil extraction using Microwave Assisted Hydro-distillation (MAHD) method on zingiberene content. In: IOP Conference Series: Earth and Environmental Science; Bogor, Indonesia. IOP Publishing; 2020.
   Google Scholar
• Gafar M, Itodo, A.U., Warra, A.A, et al. Extraction and physicochemical determination of garlic (Allium sativum L) oil. Int J Food Nutr Sci. 2012;1(2):4–7.
   Google Scholar
• Shah S, Dhawan V, Holm R, et al. Liposomes: Advancements and innovation in the manufacturing process. Adv Drug Delivery Rev. 2020;154:102–122. doi: 10.1016/j.addr.2020.07.002
   PubMed Web of Science ®Google Scholar
• Shah M, Agrawal Y. Ciprofloxacin hydrochloride-loaded glyceryl monostearate nanoparticle: factorial design of lutrol F68 And phospholipon 90G. J Microencapsul. 2012;29(4):331–343. doi: 10.3109/02652048.2011.651498
   PubMed Web of Science ®Google Scholar
• Aremu MO,Ibrahim, H., Abdullahi, A, et al. Physicochemical characteristics and fatty acid composition of ginger (Zingiber Officinale) and garlic (Allium Sativum) oils cultivated in the north-central region of Nigeria. Human Health Halal Metrics. 2023;4(1):33–40.
   Google Scholar
• Midekessa G, Godakumara K, Ord J, et al. Zeta potential of extracellular vesicles: toward understanding the attributes that determine colloidal stability. ACS Omega. 2020;5(27):16701–16710. doi: 10.1021/acsomega.0c01582
   PubMed Web of Science ®Google Scholar
• Bot F, Cossuta D, O’Mahony JA. Inter-relationships between composition, physicochemical properties and functionality of lecithin ingredients. Trends Food Sci Technol. 2021;111:261–270. doi: 10.1016/j.tifs.2021.02.028
   Web of Science ®Google Scholar
• Bunjes H, Koch MH, Westesen K. Influence of emulsifiers on the crystallization of solid lipid nanoparticles. J Pharmaceut sci. 2003;92(7):1509–1520. doi: 10.1002/jps.10413
   PubMed Web of Science ®Google Scholar
• Rasti B, Jinap S, Mozafari MR, et al. Comparative study of the oxidative and physical stability of liposomal and nanoliposomal polyunsaturated fatty acids prepared with conventional and Mozafari methods. Food Chem. 2012;135(4):2761–2770. doi: 10.1016/j.foodchem.2012.07.016
   PubMed Web of Science ®Google Scholar
• Alharbi DS, Albalawi SF, Alghrid ST, et al. Ginger oil nanoemulsion formulation augments its antiproliferative effect in Ehrlich solid tumor model. Foods. 2023;12(22):4139. doi: 10.3390/foods12224139
   PubMed Web of Science ®Google Scholar
• Lu B, Ma Q, Zhang J, et al. Preparation and characterization of bupivacaine multivesicular liposome: a QbD study about the effects of formulation and process on critical quality attributes. Int J Pharmaceut. 2021;598:120335. doi: 10.1016/j.ijpharm.2021.120335
   PubMed Web of Science ®Google Scholar
• Li Q, Cai T, Huang Y, et al. A review of the structure, preparation, and application of NLCs, PNPs, and PLNs. Nanomaterials (Basel). 2017;7(6):122–134. doi: 10.3390/nano7060122
   PubMedGoogle Scholar
• Elnaggar YS. Multifaceted applications of bile salts in pharmacy: an emphasis on nanomedicine. Int J Nanomed. 2015;3955–3971. doi: 10.2147/IJN.S82558
   PubMed Web of Science ®Google Scholar
• Sazhina N, Plashchina IG, Semenova MG, et al. Variations in the size and ζ-potential of phosphatidylcholine liposomes with incorporated nutriceuticals in the course of their initiated oxidation. Colloid J. 2020;82(1):69–75. doi: 10.1134/S1061933X20010159
   Web of Science ®Google Scholar
• Shen Y, Shen Y, Bi X, et al. Linoleic acid-modified liposomes for the removal of protein-bound toxins: An in vitro study. Int J Artif Organs. 2021;44(6):393–403. doi: 10.1177/0391398820968837
   PubMed Web of Science ®Google Scholar
• Faustino C, Serafim C, Rijo P, et al. Bile acids and bile acid derivatives: use in drug delivery systems and as therapeutic agents. Expert Opin Drug Delivery. 2016;13(8):1133–1148. doi: 10.1080/17425247.2016.1178233
   PubMed Web of Science ®Google Scholar
• Zheng G, Zheng M, Yang B, et al. Improving breast cancer therapy using doxorubicin loaded solid lipid nanoparticles: synthesis of a novel arginine-glycine-aspartic tripeptide conjugated, pH sensitive lipid and evaluation of the nanomedicine in vitro and in vivo. Biomed Pharmacother. 2019;116:109006. doi: 10.1016/j.biopha.2019.109006
   PubMed Web of Science ®Google Scholar
• Li H, Zhao X, Ma Y, et al. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Controlled Release. 2009;133(3):238–244. doi: 10.1016/j.jconrel.2008.10.002
   PubMed Web of Science ®Google Scholar
• Marwah M, Badhan RK, Lowry D. Development of a novel polymer-based carrier for deformable liposomes for the controlled dermal delivery of naringenin. J Liposome Res. 2022;32(2):181–194. doi: 10.1080/08982104.2021.1956529
   PubMed Web of Science ®Google Scholar
• Wijaya A, Wang Y, Tang D, et al. A study of lovastatin and l-arginine co-loaded PLGA nanomedicine for enhancing nitric oxide production and eNOS expression. J Mat Chem B. 2022;10(4):607–624. doi: 10.1039/D1TB01455B
   PubMed Web of Science ®Google Scholar
• Srikar Grandhi RG, Ramana G, Raasi S, et al. Study On influence of process parameters on quality of lovastatin microspheres by design of experiments. J Pharm Negat. 2022;13(7): 1799–1810.
   Google Scholar
• Zhou X, Chen Z. Preparation and performance evaluation of emulsomes as a drug delivery system for silybin. Arch Pharm Res. 2015;38(12):2193–2200. doi: 10.1007/s12272-015-0630-7
   PubMed Web of Science ®Google Scholar
• Simões MG, Hugo A, Gómez-Zavaglia A, et al. Formulation and Characterization of Stimuli-Responsive Lecithin-Based Liposome Complexes with Poly (acrylic acid)/Poly (N, N-dimethylaminoethyl methacrylate) and Pluronic® Copolymers for Controlled Drug Delivery. Pharmaceutics. 2022;14(4):735. doi: 10.3390/pharmaceutics14040735
   PubMed Web of Science ®Google Scholar
• Khan I, Yousaf S, Najlah M, et al. Proliposome powder or tablets for generating inhalable liposomes using a medical nebulizer. J Pharm Invest. 2021;51(1):61–73. doi: 10.1007/s40005-020-00495-8
   Web of Science ®Google Scholar
• Health Canadan Monograph-Lovastatin. 2017. Available from: (chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://s3-us-west-2.amazonaws.com/drugbank/cite_this/attachments/files/000/004/664/original/Health_Canada_Monograph_-_Lovastatin.PDF?1564095447)-
   Google Scholar
• FDA Label-Lovastatin (chrome-extension. 2016. Available from: //efaidnbmnnnibpcajpcglclefindmkaj/https://s3-us-west-2.amazonaws.com/drugbank/cite_this/attachments/files/000/004/661/original/FDA_Label_-_Lovastatin.pdf?1564095428)
   Google Scholar
• Zancanella P, Oliveira Daniele ML, de Oliveira BH, et al. Mitotane liposomes for potential treatment of adrenal cortical carcinoma: ex vivo intestinal permeation and in vivo bioavailability. Pharm Dev Technol. 2020;25(8):949–961. doi: 10.1080/10837450.2020.1762645
   PubMed Web of Science ®Google Scholar
• Deng F, Bae YH. Bile acid transporter-mediated oral drug delivery. JControlled Release. 2020;327:100–116. doi: 10.1016/j.jconrel.2020.07.034
   PubMed Web of Science ®Google Scholar
• Fattahi N, Shahbazi M-A, Maleki A, et al. Emerging insights on drug delivery by fatty acid mediated synthesis of lipophilic prodrugs as novel nanomedicines. J Controlled Release. 2020;326:556–598. doi: 10.1016/j.jconrel.2020.07.012
   PubMed Web of Science ®Google Scholar
• Halder J, Pradhan D, Kar B, et al. Nanotherapeutics approaches to overcome P-glycoprotein-mediated multi-drug resistance in cancer. Nanomedicine. 2022;40:102494. doi: 10.1016/j.nano.2021.102494
   PubMed Web of Science ®Google Scholar
• Neupane YR, Sabir MD, Ahmad N, et al. Lipid drug conjugate nanoparticle as a novel lipid nanocarrier for the oral delivery of decitabine: ex vivo gut permeation studies. Nanotechnology. 2013;24(41):415102. doi: 10.1088/0957-4484/24/41/415102
   PubMed Web of Science ®Google Scholar
• Yao M, McClements DJ, Xiao H. Improving oral bioavailability of nutraceuticals by engineered nanoparticle-based delivery systems. Curr Opin Food Sci. 2015;2:14–19. doi: 10.1016/j.cofs.2014.12.005
   Web of Science ®Google Scholar
• Hegazi OE, Alalalmeh SO, Alnuaimi GRH, et al. NAFLD and nutraceuticals: a review of completed phase III and IV clinical trials. Front Med. 2023;10:1227046. doi: 10.3389/fmed.2023.1227046
   Web of Science ®Google Scholar
• Zi Y, Yang K, He J, et al. Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms. Adv Drug Delivery Rev. 2022;188:114449. doi: 10.1016/j.addr.2022.114449
   PubMed Web of Science ®Google Scholar
• Ajeeshkumar KK, Aneesh PA, Raju N, et al. Advancements in liposome technology: preparation techniques and applications in food, functional foods, and bioactive delivery: a review. Compr Rev Food Sci Food Saf. 2021;20(2):1280–1306. doi: 10.1111/1541-4337.12725
   PubMed Web of Science ®Google Scholar
• Samadi M, Moradinazar M, Khosravy T, et al. A systematic review and meta‐analysis of preclinical and clinical studies on the efficacy of ginger for the treatment of fatty liver disease. Phytother Res. 2022;36(3):1182–1193. doi: 10.1002/ptr.7390
   PubMed Web of Science ®Google Scholar
• Albillos A, De Gottardi A, Rescigno M. The gut-liver axis in liver disease: pathophysiological basis for therapy. J Hepatol. 2020;72(3):558–577. doi: 10.1016/j.jhep.2019.10.003
   PubMed Web of Science ®Google Scholar
• Panjeshahin A, Mollahosseini M, Panbehkar‐Jouybari M, et al. Effects of garlic supplementation on liver enzymes: a systematic review and meta‐analysis of randomized controlled trials. Phytother Res. 2020;34(8):1947–1955. doi: 10.1002/ptr.6659
   PubMed Web of Science ®Google Scholar
• Fahmi A, Hassanen N, Abdur-Rahman M, et al. Phytochemicals, antioxidant activity and hepatoprotective effect of ginger (Zingiber officinale) on diethylnitrosamine toxicity in rats. Biomarkers. 2019;24(5):436–447. doi: 10.1080/1354750X.2019.1606280
   PubMed Web of Science ®Google Scholar