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Thermo-reversible in situ forming implant with nanostructured lipid carriers (NLC) as a delivery system for the administration of estradiol valerate

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Abstract

A thermo-reversible in situ forming implant, based on the combination of Pluronic® F-127 and Pluronic® F-68 with nanostructured lipid carriers (NLC), was formulated with the aim of achieving the sustained release of estradiol valerate (EV). EV-loaded NLC, prepared by the hot high-pressure homogenization technique, presented an entrapment efficiency of 90 ± 2.9 %, a particle size (PS) of 122 ± 11.2 nm, a polydispersity index (PDI) of 0.344 ± 0.07, and a zeta potential (ZP) of − 10.5 ± 1.3 mV. Once obtained, NLC were then included in a thermo-reversible gel (EV-loaded NLC gel), which was characterized by its rheological behavior, gelation temperature, and injectability. The in vitro release tests showed that the EV-loaded NLC gel delayed the release significantly, in comparison with a solution of the drug and with the EV-loaded NLC. The EV-loaded NLC gel and a commercially available suspension containing estradiol were administered parenterally to rabbits. A 16.8-fold greater AUC and a 40-fold higher Cmax were obtained with the EV-loaded NLC gel, compared to the commercial suspension. A rapid initial release of EV in vivo, from the EV-loaded NLC gel, suggests that it is necessary to adjust the ratio of the copolymers or to include in the gel an additive that improves gelation time and gel strength, in order to achieve a sustained release. An interesting observation was that the in vitro profile, which has a three-phase behavior, coincides with what was observed in the in vivo study.

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Funding

The authors are grateful for the financial support provided by CONACyT (Mexico), PIAPI/UNAM (Ref. 1803), and PAPIIT/UNAM (Ref. IN226119). Likewise, they want to thank Dr. Gabriel Araujo-Silva for their excellent assistance with rabbit work.

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Authors and Affiliations

  1. División de Estudios de Posgrado (Tecnología Farmacéutica), Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, 54740, Cuautitlán Izcalli, Estado de México, Mexico

    María Teresa Pineda-Hernández & Adriana Ganem-Rondero

  2. Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico

    José Trinidad Pérez-Urizar

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  1. María Teresa Pineda-Hernández
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  2. José Trinidad Pérez-Urizar
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Correspondence to Adriana Ganem-Rondero.

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Pineda-Hernández, M.T., Pérez-Urizar, J.T. & Ganem-Rondero, A. Thermo-reversible in situ forming implant with nanostructured lipid carriers (NLC) as a delivery system for the administration of estradiol valerate. Drug Deliv. and Transl. Res. 10, 1393–1402 (2020). https://doi.org/10.1007/s13346-019-00704-4

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