(T1030-05-26) 3D-Printed Short Nanofibers/Hydrogel-Based Vaginal Films as a Novel System for the Delivery of Anti-HIV Microbicide Drugs

Purpose: The study aims to contribute to combating the global AIDS epidemic by enhancing the prognosis of HIV patients. This will be achieved through the development of an innovative vaginal drug delivery system utilizing Combined Antiretroviral Therapy (cART). The system, based on advanced 3D-printed short nanofiber/film technology, is designed to administer a combination of ritonavir (RTV) and efavirenz (EFZ), tailored specifically for vaginal application. By integrating electrospinning and 3D printing technologies and optimizing formulations, the study endeavors to establish the reliability and efficacy of these 3D-printed nanocomposites in meeting therapeutic objectives, particularly in the realm of anti-HIV therapies as shown in Fig (1).

Methods: Ritonavir-loaded Polycaprolactone nanofibers were fabricated via electrospinning. Subsequently, the electrospun nanofibers were cryocut into uniform short nanofibers using the NX50 Cryostat. An optimized hydrogel matrix ink formulation containing Efavirenz was prepared by blending Efavirenz ethanolic solution with glycerin, PVP K40 solution, CS solution, and HPMC solution as shown in table1. The cryocut-prepared short nanofibers containing Ritonavir/PCL were then dispersed within the prepared EFZ/HG ink formulation. Using a 3D bioprinter, vaginal films were constructed and then tested for compatibility, mechanical properties, and drug release in a simulated vaginal medium at pH 4.5.

Results: The research investigated the development of 3D-printed short nanofiber-based vaginal films as a potential pre-exposure prophylaxis method against HIV transmission in women. An optimized formulation of 3D-printable short nanofibers/hydrogel was determined, as illustrated in Fig. (1). Subsequently, the produced vaginal films underwent various characterizations, including scanning electron microscopy studies and measurement of mechanical properties. In Fig. (2), the in vitro release profiles of Ritonavir from the formulated vaginal film revealed a gradual release of 25.8 ± 1.1% of the drug content after 45 minutes, while Efavirenz exhibited an immediate release of 59.3 ± 4.3% within the same timeframe.

Conclusion: The current study established the 3D-printing of short nanofiber-based vaginal films as a forefront pre-exposure prophylaxis approach against the sexual transmission of HIV to women. Electrospinning was used to effectively generate RIT-loaded nanofibers, which were then cryocutted into short nanofibers and disseminated into an EFZ-loaded hydrogel matrix, which was then 3D-printed into thin films using the extrusion process. The morphological and mechanical attributes of the film align with the intended characteristics of vaginal films, including thinness, ease of application, and resistance to ripping. The physicochemical properties of the 3D-printed films demonstrated Drug compatibility with the film-forming ingredients. Furthermore, the study pointed out the fast release of EFZ and some RIT that could provide immediate antiviral protection immediately following application, as well as the continuous release of RIT from the short nanofibers that could promote extended therapeutic effect.

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Zhang, Jun, et al. "Silk particles, microfibres and nanofibres: A comparative study of their functions in 3D printing hydrogel scaffolds." Materials Science and Engineering: C 103 (2019): 109784.
Xu, Tao, et al. "Electrospun polycaprolactone 3D nanofibrous scaffold with interconnected and hierarchically structured pores for bone tissue engineering." Advanced healthcare materials 4.15 (2015): 2238-2246.
Notario-Pérez, F., et al., Design, fabrication and characterisation of drug-loaded vaginal films: State-of-the-art. Journal of Controlled Release, 2020. 327: p. 477-499.
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Acknowledgements: The authors declare no financial conflict of interest.


Figure 1 Fabrication process for drug-loaded nanofibers and hydrogel ink.


Table 1. Compositions, printability, and disintegration time of different EFZ vaginal films loaded with RIT/SNFs prepared at constant concentrations of glycerol (10% w/w of the total polymeric content in the final ink formulation), and at different concentrations of HWH-PVA, LWH-PVA, PVP k40, HPMC and CS. Each component’s concentration is expressed as %w/w of the printing ink.


Figure 2. Release profiles of EFZ (a) and RIT (b) in vagina simulating medium (pH 4.5) for 72 h. Data are presented for triplicates.