Thermo-reversible in situ forming implant with nanostructured lipid carriers (NLC) as a delivery system for the administ
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ORIGINAL ARTICLE
Thermo-reversible in situ forming implant with nanostructured lipid carriers (NLC) as a delivery system for the administration of estradiol valerate María Teresa Pineda-Hernández 1 & José Trinidad Pérez-Urizar 2 & Adriana Ganem-Rondero 1
# Controlled Release Society 2020
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. Keywords Estradiol valerate . Nanostructured lipid carriers . Thermo-reversible . Hormone, replacement therapy . Pluronic
Introduction Estrogen replacement therapy in postmenopausal women has been widely used not only to relieve climacteric symptoms but also due to the beneficial effects for the prevention of osteoporosis and cardiovascular diseases. Different systems have been proposed for the administration of hormones, through a number of routes, seeking to achieve a sustained release, with constant plasma levels, which allows reducing the dosage frequency. The effect of these systems depends on the characteristics of the formulation (i.e., composition, physical form, and
* Adriana Ganem-Rondero [email protected] 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
2
Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
functional properties) and the route of administration. Oral dosage forms were for many years the most commonly used for the administration of hormones; however, alternative modes such as transdermal patches, subcutaneous implants, to
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