Tamoxifen guided liposomes for targeting encapsulated anticancer agent to estrogen receptor positive breast cancer cells: in vitro and in vivo evaluation.
Tamoxifen (TMX), an estrogen receptor (ER) antagonist, incorporated at surface of liposomes loaded with Doxorubicin (DOX), was hypothesized to serve as ligand for targeting overexpressed ERs on surface and cytosol of breast cancer cells, in addition to its synergism with DOX in killing MCF-7 cells. The TMX-DOX liposomes demonstrated mean size of 188.8±2.2nm and positive potential of+47mV, both suitable for better cellular interaction. TMX-DOX liposomes sustained DOX release in vitro (25.9%) in pH 7.4 at 48h, in comparison with 64.5% DOX release at pH 5.5. In vitro cell line studies demonstrated that TMX-DOX liposomes were more cytotoxic to ER+ve MCF-7 cells as compared to DOX liposomes, DOX solution and TMX-DOX solution (P<0.05). However, there was no statistical difference in cyto-toxicity of TMX-DOX liposomes and DOX liposomes towards ER-ve MDA-MB-231 cells. Flow cytometry and confocal studies in MCF-7 cells revealed greater cell and nuclear uptake of DOX, with TMX guided liposomes as compared to DOX liposomes and DOX solution. TMX-DOX liposomes demonstrated significantly increased inhibition of MCF-7 cell based tumor growth in nude mice (P<0.05) in comparison to DOX solution and DOX liposomes, indicative of target specificity and higher DOX accumulation at tumor site.
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400098, India.
Ankitkumar S
AS
Jain
Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai 410210, India.
Peeyush N
PN
Goel
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400098, India.
Sanket M
SM
Shah
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400098, India.
Vivek V
VV
Dhawan
Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai 410210, India.
Yuvraj
Y
Nikam
Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai 410210, India.
Rajiv P
RP
Gude
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400098, India. Electronic address: mangal.nagarsenker@gmail.com.
Mangal S
MS
Nagarsenker
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
D008024:Ligands; D011960:Receptors, Estrogen; C506643:liposomal doxorubicin; D013629:Tamoxifen; D011092:Polyethylene Glycols; D004317:Doxorubicin
Doxorubicin; Estrogen receptor; Liposomes; MCF-7 cells; Tamoxifen; Targeting