Microneedle-Array-Mediated Transdermal Delivery of GCV-Functionalized Zeolitic Imidazolate Framework-8 Nanoparticles...

Area of Science:

• Biomedical Engineering
• Materials Science
• Virology

Background:

• Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gamma-herpesvirus linked to malignant tumors and a major cause of mortality in AIDS patients.
• Ganciclovir (GCV) is a primary antiviral drug for KSHV, but its clinical use is limited by poor specificity and transmembrane delivery, causing toxic side effects.
• Effective drug delivery systems are crucial to enhance GCV concentration in target cells and mitigate KSHV progression.

Purpose of the Study:

• To develop a novel nano-delivery system for improved GCV delivery against KSHV.
• To fabricate microneedle arrays loaded with GCV encapsulated in zeolite imidazole framework-8 (ZIF-8).
• To evaluate the efficacy of the microneedle arrays in inhibiting KSHV replication in vivo.

Main Methods:

• Zeolite imidazole framework-8 (ZIF-8), a biocompatible porous material, was synthesized and loaded with Ganciclovir (GCV).
• A polydimethylsiloxane (PDMS) microneedle mold was used to fabricate microneedle arrays containing GCV@ZIF-8 nanoparticles (MN/GCV@ZIF-8).
• The microneedle arrays were assessed for skin-piercing capability and in vivo anti-KSHV activity.

Main Results:

• The fabricated MN/GCV@ZIF-8 arrays demonstrated effective skin penetration through the stratum corneum.
• The microneedle system significantly inhibited KSHV replication and cleavage in vivo.
• The nano-delivery system successfully delivered GCV to the tumor site, exerting an anti-KSHV effect.

Conclusions:

• The developed microneedle array system loaded with GCV@ZIF-8 offers a promising strategy for targeted KSHV therapy.
• This approach overcomes the limitations of conventional GCV administration, improving drug efficacy and reducing toxicity.
• The study highlights the potential of ZIF-8 based microneedles for treating KSHV infections.