Injectable Vaginal Hydrogels as a Multi-Drug Carrier for Contraception

Abstract

Injectable intravaginal hydrogels could deliver drugs systemically without hepatic first pass effect. This paper focuses on the contraceptive function of an injectable temperature-sensitive four-arm star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (4sPLGA-mPEG) block copolymer hydrogels as a carrier of three drugs. In vitro controlled release profiles were investigated via HPLC, and it showed that the cumulative release amounts of indomethacin (IMC), gestodene (GSD), and ethinyl estradiol (EE) from copolymer hydrogels could be regulated by adjusting the lactide/glycolide (LA/GA) mol ratio. In addition, in vitro release profiles of IMC, GSD, and EE well corresponded to Higuchi model. The acute toxicity of copolymer hydrogels loaded with different dosage contents multi-drug was evaluated in vivo. As to the high dosage group, the uterus was hydropic at day 1 and ulcerated at day 5, followed with intestinal adhesion. Regarding the middle dosage group, no festering of tissues was observed and, blood coagulum existed in the uterus at different days. For low dosage group, no significant tissue necrosis was found. Finally, the antifertility experiments confirmed that hydrogels loaded with the multi-drug had an excellent contraceptive effect. The above results indicated that injectable copolymer hydrogel as a multi-drug carrier was promising as a novel contraception method.

Composite Hydrogel of Poly(acrylamide) and Starch as Potential System for Controlled Release of Amoxicillin and Inhibition of Bacterial Growth

“…ese three-dimensional hydrophilic polymer networks, held together either by chemical or physical interactions [9,10], absorb large amounts of aqueous fluids [11] coupled with a high permeability to small molecules and a soft consistency, which makes them similar to living tissues [12].…”

“…eir applications encompass wound dressing uses [11], tissue engineering [13], and controlled drug delivery of a wide range of bioactive compounds [14], including antiviral drugs [10], contraceptives [12], and anticoagulants [15], among others.…”

Molecularly Imprinted Chitosan-Based Thin Films with Selectivity for Nicotine Derivatives for Application as a Bio-Sensor and Filter

“…Reports have presented cases where it was used to characterize substances like benzotriazole [ 44 ], tetracycline [ 45 ], b-estradiol, estradiol benzoate, ethynyl estradiol etc. [ 46 ], as well as the extent to which binding was feasible.…”

Application of Sol–Gels for Treatment of Gynaecological Conditions—Physiological Perspectives and Emerging Concepts in Intravaginal Drug Delivery

“…With these established benefits of VDDS, and the many limitations/unwanted effects associated with current modes of hormonal contraceptive administration, safer and more patient-friendly intravaginal hormonal contraceptives—specifically, stimuli-responsive in situ hydrogels—are gaining attention and interest [ 78 , 181 ]. It has been demonstrated that formulations containing multiple drugs are more efficient contraceptives compared to single-drug formulations [ 122 , 181 ]. In this context, an in situ pH-responsive hydrogel containing indomethacin, gestodene, and ethinyl estradiol prevented pregnancy completely compared to a control group, which presented 100% pregnancy.…”