Undergraduate Research Assistant Stevens Institute of Technology Hoboken, New Jersey, United States
Introduction: Long-acting reversible contraceptives (LARCs), such as intrauterine devices (IUDs) and contraceptive implants, are utilized by one in four sexually active women. Subdermal implants are often favored for their less invasive insertion procedures, lower maintenance requirements, and immediate reversibility. A subdermal contraceptive is a small rod inserted into the arm, releasing a study dose of progestin and/or estrogel, providing contraception by thickening cervical mucus and thinning the cervical lining. The leading subdermal contraceptive implant, Nexplanon, is a progestin-only implant that lasts up to 3 years and is over 99% effective in preventing pregnancy. However, it has significant issues, with 1 in 10 users having the device removed due to unfavorable side effects including: prolonged bleeding, irritation, depression, vaginitis, and more. These side effects are believed to be a result of inconsistent dosing and lacking biocompatibility with the current plastic material, Poly Ethylene Vinyl Acetate (EVA). This study investigates the potential of enhancing these devices through the replacement of EVA with a natural polymer, Poly Lactic-co-Glycolic Acid (PLGA). This approach aims to improve effectiveness, offering a more biocompatible solution for implanted contraception. PLGA is an FDA-approved material, utilized in a diverse set of medical applications and drug-delivery devices. The tunability of PLGA allows for controlled degradation and drug release dependent on the formulation of the polymer. The integration of PLGA into etonogestrel implants could revolutionize the field of implanted contraception, enhancing the quality of life for millions of women by providing a safer, more comfortable contraceptive option.
Materials and
Methods: In this study, a literature review was performed in which the Nexplanon implant was examined, focusing on its essential device components, flexibility, durability, and biocompatibility. Over 50 articles detailing the mechanical, chemical, and surface properties of EVA and potential alternatives were reviewed. The inclusion criteria encompassed articles sourced from academic or professional platforms, the majority of which were peer-reviewed. The search incorporated keywords such as PEVA, PLGA, Implant, Drug Delivery, LARC, Contraceptive Implant, Biocompatibility, Nexplanon, Efficacy, and Properties. The exclusion criteria comprised structures frequently made of PLGA that were irrelevant to the study, including scaffolds, cancer, and ophthalmic structures. Numerous research articles were sourced from the reference sections of other credible articles. Following the literature review, PLGA was selected as a suitable alternative material (analyzed in Table 1). A model was developed in SolidWorks to compare the durability and flexibility of the two materials using a static finite element analysis. For this model, the external cylinder of the device was fixed, as the subdermal implant will be held in place by surrounding tissue. 100 Newtons of force were applied to each at the top, bottom, and sides of the implant. The analysis revealed a negligible difference in the flexibility and mechanical strength of the materials. Subsequently, a series of tables were constructed to compare the biocompatibility and efficacy of the materials. These tables provided a comparison of the mechanical properties of each material individually, as well as the bulk and surface properties, biocompatibility, and drug delivery efficacy.
Results, Conclusions, and Discussions: Research conducted on the Nexplanon device identified two major flaws that impact its effectiveness user experience: a lack of biocompatibility and inconsistent dosing. The current material used in the construction of this device is Ethylene-vinyl acetate (EVA), a non-degradable, biocompatible, insoluble, and non-toxic polymer known for its high toughness and yield strength. However, Poly Lactic co-glycolic acid (PLGA) has emerged as a promising alternative. PLGA is a biodegradable and biocompatible polymer that not only matches the strength of EVA, but also provides a controlled, long-duration drug release, ensuring a steady dosage over time. This unique property makes PLGA a suitable replacement for EVA in the construction of contraceptive implants. PLGA microspheres have gained popularity in the field of biomedicine due to their biodegradability and biocompatibility. These microspheres are safe for implantation and break down harmlessly within the body. The permeability of PLGA microspheres can be adjusted by modifying factors such as particle size, composition, and porosity, which contributes to the integrity and durability of implants. One major benefit of using PLGA is its tunability. By altering the ratio of glycolic acid to lactic acid, the mechanical properties of the polymer can be adjusted, including the degradation and drug release rates. This allows for more accurate and consistent dosing, making PLGA ideal for contraceptive implant applications. However, it’s important to note that PLGA degrades more quickly than EVA, requiring more frequent insertions.
Finite element analysis was performed to compare the mechanical properties of EVA and PLGA. The results (Figures 1 and 2) showed that the strain experienced by PLGA was negligible, indicating that the two materials had similar mechanical strength and flexibility. This allowed the research to focus on the biocompatibility and drug delivery efficacy, of the two materials compared in Table 2. In conclusion, the use of PLGA in the construction of contraceptive implants could revolutionize the field of women’s health. Its biodegradability, biocompatibility, and controlled drug release make it an excellent choice for biomedical applications. The potential impact on women’s health is considerable, promising safer, more comfortable, and more personalized contraceptive solutions that could transform women’s experience with contraception.
Acknowledgements (Optional): I would like to extend my deepest gratitude to Dr. Sally Shady for her guidance and encouragement throughout this research. Her expertise and unwavering support have been pivotal in my development as a student in this field.
