Triptorelin nanoparticle-loaded microneedles for use in assisted reproductive technology

Abstract

Triptorelin is a first-line drug for assisted reproductive technology (ART), but the low bioavailability and frequent subcutaneous injection of triptorelin impair the quality of life of women preparing to become pregnant. We report silk fibroin (SF)-based microneedles (MNs) for transdermal delivery of triptorelin-loaded nanoparticles (NPs) to improve bioavailability and achieve safe and efficacious self-administration of triptorelin. Triptorelin was mixed into an aqueous solution of SF with shear force to prepare NPs to control the release and avoid the degradation of triptorelin by enzymes in the skin. Two-step pouring and centrifugation were employed to prepare nanoparticles-encapsulated polymeric microneedles (NPs-MNs). An increased β-sheet content in the conformation ensured that NPs-MNs had good mechanical properties to pierce the stratum corneum. Transdermal release of triptorelin from NPs-MNs was increased to ∼65%. The NPs-MNs exhibited a prolonged drug half-life and increased relative bioavailability after administration to rats. Surging levels of luteinizing hormone and estradiol in plasma and their subsequent prolonged downregulation indicate the potential therapeutic role of NPs-MNs in ART regimens. The triptorelin-loaded NPs-MNs developed in this study may reduce the physical and psychological burden of pregnant women using ART regimens.

Keywords:

• Assisted reproductive technology
• triptorelin
• silk fibroin
• nanoparticles
• microneedles

Author contributions

Xiaoyan Lu: conceptualization, methodology, investigation, writing – original draft writing – original draft, and writing – review and editing; Yiying Sun: software, resources, and writing – original draft; Meishan Han: formal analysis, investigation, and writing – original draft; Daoyuan Chen: investigation, methodology, and data curation; Xiaoyan He: project administration and data curation; Siqi Wang: methodology, investigation, and data curation; Kaoxiang Sun: conceptualization, writing – review and editing, supervision, project administration, and funding acquisition.

Ethical approval

All animal experiments were approved by the Animal Ethical and Welfare Committee of Yantai University (YTU-2012010) and were in accordance with the guidelines for the use of experimental animals set by the European Union. All animals were raised at constant temperature (25 ± 2 °C) and humidity (55 ± 5%) and fed with commercial aseptic food. All animals were employed to evaluate the therapeutic effects of triptorelin nanoparticle-loaded microneedles and every effort was made to minimize animal suffering and reduce the number of animals used in the experiments. The study has adhered to the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability statement

All data and materials of this study can be obtained from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the ‘Major New Drug Creation’ Major Science and Technology Project (2018ZX09301017003).