Development of Tamoxifen In Situ Gel Nanoemulsion for Ocular Delivery in Photoreceptor Degeneration Disorder: In Vitro Characterization, 131I-Radiolabeling, and In Vivo Biodistribution Studies

Abstract

Abstract Purpose The aim of our work is to develop an in situ ocular gellan gum–based nanoemulsion (NE) of tamoxifen TAM as an alternative drug delivery system to the oral route for the treatment of photoreceptor degeneration disorder. Method Six pseudoternary phase diagrams were developed using oil (oleic acid), surfactants (Tween 80 or Tween 20), a co-surfactant (polyethylene glycol 400), and water. The particle size, polydispersity index, and zeta potential of the developed systems were all measured. The safety of ocular application of the optimum system was established via in vivo histopathological investigation. To track the biodistribution of the optimum gel, iodine-131 ( 131 I) was incorporated into the gel via coupling with TAM via direct electrophilic substitution reaction. Results Based on the obtained results, TAMNE-1 was chosen as the optimal system, with PS = 140.20 ± 1.50 nm, ZP = − 27.86 ± 1.13 mV, and PDI = 0.20 ± 0.00%. In vitro release displayed a prolonged and sustained release of TAMNE-1 gel compared to TAM solution (plain eye drop). Transparent in situ TAMNE-1 gel was developed after the incorporation of the TAMNE-1 system into gellan gum aqueous solution (0.3% w/w). In this study, TAM was successfully radiolabeled with 131 I for subsequent evaluation of the efficacy of the developed in situ gel system (TAMNE-1 gel) in vivo. The developed TAMNE-1 gel system was nonirritant and safe and the biodistribution studies showed better retention of TAMNE-1 gel than plain TAM eye drops. Conclusion The developed TAMNE-1 gel is able to enhance the ocular bioavailability of TAM and can go further with clinical evaluation. Graphic Abstract

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