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Exploring uterine targeting potential of 99mTc-Paclitaxel loaded ultradeformable vesicles designed for endometrial cancer

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DOI: 10.1016/j.jddst.2023.104154

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Paclitaxel; Ultradeformable vesicles; Intravaginal route; Endometrial cancer

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The study aimed to investigate the uterine targeting potential of Paclitaxel (PTX) loaded ultradeformable vesicles (PTX-UDV) after intra-vaginal administration. PTX-UDV were formulated and characterized, and the radiolabeled PTX (99mTc-PTX) was evaluated for its stability and binding efficiency. The biodistribution of 99mTc-PTX loaded UDV and plain 99mTc-PTX was assessed in rabbits after intra-vaginal administration.
Purpose: The present investigation aimed to explore uterine targeting potential of Paclitaxel (PTX) loaded ultradeformable vesicles (PTX-UDV) after intra-vaginal administration.Methods: PTX-UDV were formulated by thin film hydration technique using phospholipids and edge-activator combination and characterized for drug entrapment, loading, vesicle size, zeta-potential, deformability index, shape and surface morphology and in-vitro drug release. PTX was radiolabelled using 99mTc and evaluated for its radiochemical purity, in-vitro stability and binding efficiency by DTPA transchelation study. 99mTc labelled PTX (99mTc-PTX) loaded UDV and plain 99mTc-PTX was assessed for biodistribution in New Zealand white female rabbits after intra-vaginal administration.Results: The formulation exhibited high entrapment efficiency of 91.27 +/- 1.26% with 8.92 +/- 0.12% drug loading. Vesicle size was 214.2 +/- 4.22 nm with-34.3 +/- 2.32 mV zeta-potential. Radiochemical Purity of 99mTc-PTX was 96.5 +/- 1.2% after 48h. In-vitro stability of 99mTc-PTX was 94.6 +/- 1.3% and 91.9 +/- 1.5% in normal saline and serum respectively after 48h. The targeting efficiency of 99mTc-PTX loaded UDV was 20 times higher with significantly low systemic absorption than plain labelled drug complex.Conclusion: The outcomes of study reveal favoured uptake of 99mTc-PTX loaded UDV formulation by uterus and localization for prolonged period of time when administered via intra-vaginal route.

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