Efficacy of Emu Oil Transfersomes for Local Transdermal Delivery of 4-OH Tamoxifen in the Treatment of Breast Cancer

Abstract

Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC–MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.

Influence of CYP2D6 and its polymorphic forms on the metabolism of tamoxifen in therapy of luminal forms of breast cancer

“…Patients with concentrations below 5.97 ng/ml had a significantly increased risk of recurrence, and conversely, patients with concentrations above 5.97 ng/ml had a significantly lower risk of breast cancer recurrence and progression. There is an opinion that it is possible that the problem of slow metabolizers could be solved by increasing the dose of tamoxifen from the standard 20 mg to 40 mg, and many literary sources claim this, because only 24% of slow metabolizers had the required level of endoxifen concentration in the blood plasma [6,35,40]. But there are researchers who did not get similar results and there is still no single complete and clear idea about the effect of different allelic variants of CYP2D6 on the effectiveness of tamoxifen treatment [5,7,10,11,15,16,22,30].…”

L-Cysteine-Modified Transfersomes for Enhanced Epidermal Delivery of Podophyllotoxin

“…A large amount of ethanol in a POD tinctur could promote drug penetration by damaging the stratum corneum of skin [46]. The dru permeation-promoting effect of the transfersomes might be attributed to the followin (1) The surfactant added in the formulation could increase the fluidity of the stratum corneum lipid and increase the space between the keratinocytes [47], (2) since the evap oration of water on the skin surface would cause it to lose some water, the transfersome would sense the penetration gradient and try to avoid dryness by moving toward th deeper skin along this gradient [48], (3) the transfersomes have ultra-deformable elasti ity and flexibility, enabling them to squeeze through the smaller pores betwee keratinocytes [49], and (4) the small size of the transfersomes could increase the absorbe surface area [50]. On the other hand, the POD-LCTs provided significantly lower dru penetration through the skin compared with the POD-Ts (p < 0.05).…”

Lycorine transfersomes modified with cell-penetrating peptides for topical treatment of cutaneous squamous cell carcinoma

“…In particular, nanoparticles, such as nanoemulsions [ 13 ], liposomes [ 14 , 15 ], lipid nanoparticles [ 16 , 17 ], and liquid crystals [ 18 ], are potential vehicles for delivering drugs through the skin because of their appropriate size, lipid composition with improved permeability, and easy surface modification [ 19 ]. Among them, transfersomes exhibit great potential in delivering anticancer drugs and improving skin penetration efficiency [ 20 – 23 ].…”