Injectable In Situ Forming Depot Systems for Long‐Acting Contraception

Abstract

Up to date, no long‐acting reversible contraceptive (LARC) is developed to be injectable through needles smaller than 18 G and can also provide contraception for more than 3 months after single injection. In this study, injectable polymeric in situ forming depot (ISD) systems are developed to have injectability through 21–23 G needles, and capability of sustained release of levonorgestrel (LNG) for at least 7 months in vitro and in vivo after single subcutaneous injection in rats. The systems are polymeric solutions composed of biodegradable poly(lactide‐co‐glycolide) and poly(lactic acid) polymers dissolved in a mixture of solvents like N‐methyl‐2‐pyrrolidone and benzyl benzoate or triethyl citrate. LNG released from ISD systems successfully suppressed the estrous cycle of rats at plasma concentration above 0.35 ng mL−1. At the end of the treatment, when LNG plasma concentration drops down to be nondetectable, predictable return of fertility is observed in rats. The designed ISD systems have great potential to be further developed into robust injectable LARCs that can be injected through a 21 G or smaller needle and achieve a variety of contraception durations with high patient compliance and low cost.

Nanotechnology in reproductive medicine: Opportunities for clinical translation

“…The low-dose insemination of microfluidic sorted spermatozoa improved fertility, leading to successful production of live births. [137] 3. Contraception An in situ depot system was developed, composed of biodegradable poly(lactide-co-glycolide) and poly (lactic acid) polymers encapsulating a contraceptive agent (levonorgestrel) for sustained delivery via intravenous administration.…”

“…Contraception An in situ depot system was developed, composed of biodegradable poly(lactide-co-glycolide) and poly (lactic acid) polymers encapsulating a contraceptive agent (levonorgestrel) for sustained delivery via intravenous administration. [138] MRI, magnetic resonance imaging; NSAIDs, nonsteroidal anti-inflammatory drugs; hCG, human chorionic gonadotropin; SiNc, silicon naphthalocyanine; TP, treponema pallidum. Domain…”

Advances in microneedle patches for long-acting contraception

“…Polymeric biodegradable MN patches are also suitable for long-acting contraception because biodegradable polymers have been used in subcutaneous implants [50] or in in situ injections, thus forming a hormone depot [51]. Unlike dissolvable MN patches, biodegradable MN patches are usually made of biodegradable polymers, such as poly[lactide-co-glycolide] (PLGA) [52], poly-lactic acid (PLA) [53], or polycaprolactone (PCL) [54], that continuously release drug from embedded MNs in the skin due to their slow degradation [55].…”