Drospirenone (DROP) is a highly effective, low-toxicity, safe new generation progestin that counteracts estrogen-related sodium retention, is well tolerated, and has a positive effect on premenstrual syndrome (PMS). However, the low water solubility of DROP and its chemical instability resulted in low bioavailability. In this study, we developed a two-step delivery system to enhance drospirenone’s solubility and stability. We prepared a drospirenone liposome complex to optimize the encapsulation process and achieve an encapsulation efficiency of (84.9 ± 0.73) %, with an 878-fold increase in solubility under optimal conditions. To address the instability of high drug-loading liposomes, we immobilized the drospirenone liposome inclusion complex using a cellulose-based hydrogel. The system achieved uniform loading of liposomes in the hydrogel, as confirmed by SEM and FTIR analysis. 0.5 g hydrogel can be loaded with up to 96.48 mg drospirenone, and the encapsulation efficiency is (80.4 ± 1.17%). It was indicating the potential for wider application of drospirenone with enhanced water solubility and improved stability. At the same time, it also provides support for sustained-release systems or large dose drug delivery.
At present, contraceptive drugs such as Drospirenone (DROP) encounter challenges stemming from their abbreviated half-life and constrained efficacy. Therefore, the imperative arises to formulate innovative strategies that not only prolong the duration of action but also enhance the overall effectiveness of these drugs. This study introduces a two-step delivery system designed to overcome the limitations associated with DROP applications. Initially, a Drospirenone liposome (LIP/DROP) complex was meticulously prepared. Subsequently, this complex was immobilized within a cellulose-based hydrogel, constructed from aldehyde-replaced oxidized regenerated cellulose (AC) and chitosan (CS), employing Schiff base reaction crosslinking. The encapsulation efficiency achieved an impressive 84.9% (±0.73), accompanied by an 878-fold increase in solubility. Notably, each 0.35 g of the hydrogel demonstrated the capacity to load 96.48 mg of DROP. TEM was used to observe the particle size and morphology of LIP/DROP. SEM and FTIR were employed to investigate the structure and surface morphology of the prepared hydrogel and AC. The properties of the hydrogel related to the application of drug delivery, including swelling, mechanical, bacterial inhibition, and cytotoxicity were meticulously investigated. Moreover, the drug release rate of the prepared LIP hydrogel was assessed over 400 h (9%–40%), demonstrating its potential for sustained release of DROP. These improvements in solubility and stability offer promise for expanding the utilization of DROP in contraceptive applications.
Progestogens, primarily used in assisted reproduction and tocolytic therapy, have emerged as environmental pollutants due to their widespread use in medicine and aquaculture. Their release into various ecosystems has raised concerns about their potential neurodevelopmental effects. Drospirenone (DRS), an extensively used synthetic progestin, was identified in bioinformatic analysis as a potential disruptor of NMDA receptors (NMDARs), crucial for neuronal signaling. To investigate this, zebrafish embryos were exposed to DRS from 2 h post-fertilization (hpf) to 14 days post-fertilization (dpf). Behavioral assays revealed that DRS exposure impaired locomotor activity, reduced anxiety-like responses, and diminished social behaviors. Quantitative PCR and immunofluorescence staining showed that DRS disrupted the expression of several NMDAR subunits, suppressed apoptosis, and promoted neuronal proliferation in the embryonic brain. Co-exposure with NMDA, an NMDAR agonist, reversed the neurobehavioral deficits, normalized NMDARs expression, and restored apoptosis-proliferation balance. Molecular docking, DARTS assays, and downstream marker measurements indicated target engagement between DRS and the Grin1 and Grin2 subunits of NMDAR, suggesting that DRS may alter receptor conformation and function. In conclusion, DRS induces significant neurodevelopmental toxicity in zebrafish larvae, likely by suppressing NMDAR activity and disrupting neuronal apoptosis and proliferation. These findings highlight potential risks of DRS to aquatic life and human health.
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