{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:45:52Z","timestamp":1776851152216,"version":"3.51.2"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Common Wealth Commission UK","award":["INCN-2013-44"],"award-info":[{"award-number":["INCN-2013-44"]}]},{"DOI":"10.13039\/501100000303","name":"INSPIRE","doi-asserted-by":"crossref","award":["IF120229"],"award-info":[{"award-number":["IF120229"]}],"id":[{"id":"10.13039\/501100000303","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This project aimed at the formulation of dual drug entrapped liposomes held as freeze-dried intravaginal rod insert (IVR), to be administered by vaginal route for uterine targeting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Liposomes were formulated by dehydration\u2013rehydration method using 3 : 1 molar ratio of1,2-distearoyl-sn-glycero-3-phosphocholine : Cholesterol. Characterization was done for vesicle size, zeta potential, entrapment efficiency, surface morphology and % loading.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Spherical and discrete vesicles of size 354 nm were observed in transmission electron microscopy (TEM) image. The entrapment efficiency of 90.91% and 74.3% w\/w was obtained for Raloxifene Hydrochloride (RLX) and Leuprolide acetate (LA) respectively. Drug release was sustained for 6 days. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed that dual drug entrapped liposomal formulation show significant cytotoxicity, as also confirmed by higher apoptosis in cell cycle analysis and apoptosis studies (FACS) analysis. Pharmacodynamic studies in New Zealand white female rabbits revealed that intravaginal administration of RLX-LA entrapped liposomal formulation shows considerable fibroid regression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Uterine targeting of liposomal RLX-LA suggests its potential to solve the limitations of the presently available therapeutic options.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgab003","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T20:11:46Z","timestamp":1611691906000},"page":"653-663","source":"Crossref","is-referenced-by-count":6,"title":["Development of intravaginal rod insert bearing liposomal raloxifene hydrochloride and Leuprolide acetate as a potential carrier for uterine targeting"],"prefix":"10.1093","volume":"73","author":[{"given":"Arpita","family":"Patel","sequence":"first","affiliation":[{"name":"Shri G.H. Patel Pharmacy Building, Centre for Postgraduate Studies in Pharmacy, TIFAC Core in NDDS, Donor\u2019s Plaza, Fatehgunj , Vadodara,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul","family":"Dhande","sequence":"additional","affiliation":[{"name":"Shri G.H. Patel Pharmacy Building, Centre for Postgraduate Studies in Pharmacy, TIFAC Core in NDDS, Donor\u2019s Plaza, Fatehgunj , Vadodara,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4825-9543","authenticated-orcid":false,"given":"Hetal","family":"Thakkar","sequence":"additional","affiliation":[{"name":"Shri G.H. Patel Pharmacy Building, Centre for Postgraduate Studies in Pharmacy, TIFAC Core in NDDS, Donor\u2019s Plaza, Fatehgunj , Vadodara,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"issue":"3","key":"2024103012060533500_CIT0001","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/S0015-0282(98)00208-8","article-title":"A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata","volume":"70","author":"Marshall","year":"1998","journal-title":"Fertil Steril."},{"issue":"1","key":"2024103012060533500_CIT0002","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1471-7697(02)00003-5","article-title":"The medical management of endometriosis","volume":"2","author":"Teirney","year":"2002","journal-title":"Rev Gynaecol Pract."},{"issue":"1\u20132","key":"2024103012060533500_CIT0003","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0303-7207(99)00199-9","article-title":"Expression of GnRH receptor gene in human ectopic endometrial cells and inhibition of their proliferation by leuprolide acetate","volume":"159","author":"Borroni","year":"2000","journal-title":"Mol Cell Endocrinol."},{"issue":"2","key":"2024103012060533500_CIT0004","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ddstr.2004.08.021","article-title":"Drug therapies for uterine fibroids: a new approach to an old problem","volume":"1","author":"Nowak","year":"2004","journal-title":"Drug Discov Today Ther Strateg."},{"issue":"3","key":"2024103012060533500_CIT0005","doi-asserted-by":"crossref","first-page":"276","DOI":"10.7150\/ijms.7627","article-title":"Comparison of the inhibitory effect of gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM), antiprogesterone on myoma cell proliferation in vitro","volume":"11","author":"Chung","year":"2014","journal-title":"Int J Med Sci."},{"key":"2024103012060533500_CIT0006","volume-title":"Vaginal Drug Delivery Systems","author":"Neves","year":"2008","edition":"eds."},{"key":"2024103012060533500_CIT0007","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1749-6632.1997.tb48550.x","article-title":"The first uterine pass effect","volume":"828","author":"Zeigler","year":"1997","journal-title":"Ann N Y Acad Sci."},{"issue":"1\u20132","key":"2024103012060533500_CIT0008","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ijpharm.2008.08.021","article-title":"Microemulsion based vaginal gel of fluconazole: formulation, in vitro and in vivo evaluation","volume":"365","author":"Bachhav","year":"2009","journal-title":"Int J Pharm."},{"issue":"2","key":"2024103012060533500_CIT0009","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0378-5173(97)00135-X","article-title":"Liposomes in drug delivery: progress and limitations","volume":"154","author":"Sharma","year":"1997","journal-title":"Int J Pharm."},{"issue":"11","key":"2024103012060533500_CIT0010","first-page":"979","article-title":"Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes","volume":"2","author":"Kirby","year":"1984","journal-title":"Biotechnology"},{"issue":"1","key":"2024103012060533500_CIT0011","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ejpb.2010.10.010","article-title":"Sustained release of proteins from a modified vaginal ring device","volume":"77","author":"Morrow","year":"2011","journal-title":"Eur J Pharm Biopharm."},{"issue":"5","key":"2024103012060533500_CIT0012","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ejps.2012.02.003","article-title":"Development of liposome gel based formulations for intravaginal delivery of the recombinant HIV-1 envelope protein CN54gp140","volume":"46","author":"Gupta","year":"2012","journal-title":"Eur J Pharm Sci."},{"issue":"9","key":"2024103012060533500_CIT0013","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1080\/10717544.2016.1177137","article-title":"A gamma scintigraphy study to investigate uterine targeting efficiency of raloxifene-loaded liposomes administered intravaginally in New Zealand white female rabbits","volume":"23","author":"Patel","year":"2016","journal-title":"Drug Deliv."},{"issue":"2","key":"2024103012060533500_CIT0014","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3109\/08982100903161449","article-title":"Development and characterization of minoxidil-loaded liposomal system for delivery to pilosebaceous units","volume":"20","author":"Jain","year":"2010","journal-title":"J Liposome Res."},{"key":"2024103012060533500_CIT0015","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.talanta.2014.01.034","article-title":"Experimental design and multiple response optimization. Using the desirability function in analytical methods development","volume":"124","author":"Candioti","year":"2014","journal-title":"Talanta."},{"issue":"1","key":"2024103012060533500_CIT0016","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.fertnstert.2004.12.058","article-title":"Antiproliferative and proapoptotic effects of raloxifene on uterine leiomyomas in postmenopausal women","volume":"84","author":"Palomba","year":"2005","journal-title":"Fertil Steril."},{"issue":"4","key":"2024103012060533500_CIT0017","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/humupd\/5.4.365","article-title":"New hypotheses. Transvaginal progesterone: evidence for a new functional\u2019portal system\u2019flowing from the vagina to the uterus","volume":"5","author":"Cicinelli","year":"1999","journal-title":"Hum Reprod Update."},{"issue":"1\u20132","key":"2024103012060533500_CIT0018","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ijpharm.2012.03.036","article-title":"Characterisation of protein stability in rod-insert vaginal rings","volume":"430","author":"Pattani","year":"2012","journal-title":"Int J Pharm."},{"issue":"1\u20132","key":"2024103012060533500_CIT0019","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0378-5173(02)00461-1","article-title":"Positively charged nanoparticles for improving the oral bioavailability of cyclosporin-A","volume":"249","author":"El-Shabouri","year":"2002","journal-title":"Int J Pharm"},{"issue":"10","key":"2024103012060533500_CIT0020","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1016\/j.bbamem.2007.05.003","article-title":"Lipid tail chain asymmetry and the strength of membrane-induced interactions between membrane proteins","volume":"1768","author":"Dan","year":"2007","journal-title":"Biochim Biophys Acta (BBA)-Biomembr."},{"issue":"1\u20132","key":"2024103012060533500_CIT0021","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijpharm.2004.07.010","article-title":"Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability","volume":"285","author":"Mohammed","year":"2004","journal-title":"Int J Pharm."},{"issue":"1","key":"2024103012060533500_CIT0022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-4165(85)90174-6","article-title":"Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection","volume":"839","author":"Senior","year":"1985","journal-title":"Biochim Biophys Acta (BBA)-Gen Subj."},{"issue":"1\u20132","key":"2024103012060533500_CIT0023","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J Immunol Meth."},{"issue":"13","key":"2024103012060533500_CIT0024","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1093\/jnci\/90.13.967","article-title":"Antiestrogenic action of raloxifene and tamoxifen: today and tomorrow","volume":"90","author":"Craig Jordan","year":"1998","journal-title":"J Nat Cancer Inst."},{"issue":"5","key":"2024103012060533500_CIT0025","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1210\/er.2012-1014","article-title":"GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies","volume":"33","author":"Limonta","year":"2012","journal-title":"Endocr Rev."},{"issue":"1","key":"2024103012060533500_CIT0026","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1021\/mp034002c","article-title":"Sustained cytoplasmic delivery of drugs with intracellular receptors using biodegradable nanoparticles","volume":"1","author":"Panyam","year":"2004","journal-title":"Mol Pharm."},{"issue":"3","key":"2024103012060533500_CIT0027","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s13346-015-0220-8","article-title":"Influence of cholesterol on liposome stability and on in vitro drug release","volume":"5","author":"Briuglia","year":"2015","journal-title":"Drug Deliv Transl Res."}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/73\/5\/653\/60218428\/rgab003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/73\/5\/653\/60218428\/rgab003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T16:47:54Z","timestamp":1730306874000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/73\/5\/653\/6144891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,1]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5,1]]},"published-print":{"date-parts":[[2021,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgab003","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,1]]},"published":{"date-parts":[[2021,5,1]]}}}