Introduction: Estradiol Valerate (EV), an estrogen, has been used in the post-menopausal hormone replacement therapy. Decreased levels of estradiol after menopause, results in different symptoms such as hot flashes, night sweats, insomnia, increased fatigue, irritability, depression, cardiovascular disease and osteoporosis.
NLC are composed by a mixture of solid and liquid lipids, resulting in a little-ordered crystal lattice, attaining high drug encapsulation.
Thermo-reversible in situ forming implants of Poloxamer 407 (P-407) consist of low viscosity transparent solutions, capable of being transformed into solid gels, once they reach the corporal temperature. This feature allows the formation of a sustained release reservoir.
The aim of this work was to develop EV loaded NLC, included in a thermo-reversible implant of in situ formation, capable of achieving the sustained release of EV.
Methods: NLC were prepared by the hot high pressure homogenization technique and were characterized by average particle size (PS), polydispersity index (PDI), zeta potential (ZP) by dynamic light scattering, and entrapment efficiency (EE) using a centrifugation method to separate the free drug from that encapsulated in the NLC.
P-407 gels were prepared by the cold method, with or without NLC. The sol-gel temperature was determined using the tube inversion method and by viscosity measurements, performed by placing gels on a digital viscometer plate in a temperature range of 10 to 40°C, at 50 rpm using no. 1 circular spindle.
Results and Discussion: NLC with an average PS of 242.73 nm, and PDI of 0.307, were obtained. A ZP of -10.3 mV translates into a system with good physical stability. The EE was 92.72%, attaining high drug encapsulation.
Below 37 °C the P-407 system was fluid enough to be injected, occurring the sol-gel transition at 37 °C, ensuring the in situ formation of an implant, and consequently the sustained release of EV.
Conclusions: NLC with good characteristics of PS, PDI and ZP were obtained, with high EE. Incorporation of NLC into a P-407 gel had the proper conditions to form a sustained delivery system for EV.
Acknowledgement: To PAPIIT/UNAM (Ref. IN216016).
Targeted drug delivery and nanocarriers , Nanobiology and nanobiosystems , Nanofabrication, nanoprocesing & nanomanufacturing
