Longer Acting Injectable: Continuous, Linear Release of a Progestin Contraceptive From an Oxidized Porous Silicon Host

Progestin drugs are loaded into a mesoporous silicon dioxide host by melt-infiltration. Drugs that decompose at or close to their melting point can be loaded by the addition of cholesterol, which acts as a melting point suppressor. High mass loading of the drug is achieved, and dissolution of the composite is controlled by the nanoscale properties of the oxide host, providing a linear, near zero-order drug release profile.

Abstract

Maintaining stable drug concentrations in the bloodstream is a challenge for injectable hydrophobic progestin contraceptives. This work investigates porous silicon dioxide (pSiO₂) microparticles as a delivery vehicle for progestins via melt-infiltration of drugs into the mesopores. The pSiO₂ is prepared through electrochemical anodization of single-crystalline silicon followed by thermal oxidation, yielding vertically oriented pores (≈50 nm diameter) with porosity varied (between 35–75%) to optimize drug loading and release. Among the progestins tested, etonogestrel and levonorgestrel (LNG) decompose near their melting points, preventing melt infiltration. However, addition of 20% cholesterol by mass suppresses the melting point of LNG sufficiently to enable loading without degradation. Mass loadings exceeding 50% (drug: drug + carrier) are achieved for segesterone acetate (SEG) and LNG, retaining drug crystallinity as confirmed by X-ray diffraction. In vitro, both SEG and LNG-loaded pSiO₂ display sustained drug release for up to 3 months, with reduced burst release, more constant steady-state concentrations, and a substantially reduced tail compared to pure LNG or SEG, or SEG loaded into pSiO₂ from a chloroform solution. In a pilot in vivo study, SEG-loaded pSiO₂ microparticles are well tolerated in 20-week-old female rats over a 25-week period, with no signs of toxicity.