Inhibition of breast cancer with transdermal tamoxifen-encapsulated lipoplex

Abstract

BackgroundTamoxifen is currently used for the treatment of both early and advanced estrogen receptor (ER) positive breast cancer in pre- and post-menopausal women. However, using tamoxifen routinely to inhibit endogenous or exogenous estrogen effects is occasionally difficult because of its potential side effects.ObjectivesThe aim of this study is to design a local drug delivery system to encapsulate tamoxifen for observing their efficacy of skin penetration, drug accumulation and cancer therapy.MethodsA cationic liposome-PEG-PEI complex (LPPC) was used as a carrier for the encapsulation of tamoxifen and forming ‘LPPC/TAM’ for transdermal release. The cytotoxicity of LPPC/TAM was analyzed by MTT. The skin penetration, tumor growth inhibition and organ damages were measured in xenograft mice following transdermal treatment.ResultsLPPC/TAM had an average size less than 270 nm and a zeta-potential of approximately 40 mV. LPPC/TAM displayed dramatically increased the cytotoxic activity in all breast cancer cells, especially in ER-positive breast cancer cells. In vivo, LPPC drug delivery helped the fluorescent dye penetrating across the skim and accumulating rapidly in tumor area. Administration of LPPC/TAM by transdermal route inhibited about 86 % of tumor growth in mice bearing BT474 tumors. This local treatment of LPPC/TAM did not injury skin and any organs.ConclusionLPPC-delivery system provided a better skin penetration and drug accumulation and therapeutic efficacy. Therefore, LPPC/TAM drug delivery maybe a useful transdermal tool of drugs utilization for breast cancer therapy.

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“…22 LPPC can be administered through intravenous injection and/or transdermal treatment. 20,22,23 Both treatments display efficient tumor growth inhibition due to a large amount of drug accumulation. 20,22,23 The properties of LPPCs allow them to strongly capture antigens or immunomodulators on their surfaces and be used as an adjuvant to trigger Th2 immune responses and antibody class switch.…”

“…20,22,23 Both treatments display efficient tumor growth inhibition due to a large amount of drug accumulation. 20,22,23 The properties of LPPCs allow them to strongly capture antigens or immunomodulators on their surfaces and be used as an adjuvant to trigger Th2 immune responses and antibody class switch. 24 LPPCs also strongly captured antibodies for specific drug delivery 25 and captures proteins for intracellular protein therapy.…”

Novel Tamoxifen Nanoformulations for Improving Breast Cancer Treatment: Old Wine in New Bottles

“…This system achieved sustained release of TAM, with 50% drug molecules released within three hours, and 95% of drug released after 30 h, as evidenced using in vitro release experiments. In another study conducted by Lin et al, a cationic liposome-PEG-polyethylenimine (PEI) complex (LPPC) was used as a nanocarrier, designed specifically for the local delivery and transdermal release of TAM [60]. The LPPC/TAM demonstrated a dramatic increase of activity against all BC cases, especially in ER+ BC cells.…”

“…The LPPC/TAM demonstrated a dramatic increase of activity against all BC cases, especially in ER+ BC cells. Besides the efficacy of LPPC/TAM complexion to most breast cancer cell lines, the local administration of LPPC/TAM did not induce skin or organ injury, suggesting their significant potential as a transdermal treatment for breast cancer [60]. Passive delivery of TAM-loaded-nanosystems to tumours via the enhanced permeability and retention (EPR) effect.…”

The Effect of Solid Lipid Nanoparticles on Tamoxifen-Resistant Breast Cancer Cells

“…In the literature, different nanoparticle formulations (chitosan, liposome, polymeric nanoparticles, etc.) were developed for Tam [16][17][18]. SLN is especially a good carrier for Tam due to providing its anti-tumoral activity, increasing the solubility of the drug and facilitating the entrapment of high amounts of the drug in the nanoparticles [19].…”