Formulation Development of Mucoadhesive Transnasal Microneedles for Naloxone and Atipamezole Delivery Toward Xylazine–Opioid Overdose Intervention
Abstract
The increasing prevalence of xylazine-adulterated opioid overdoses necessitates delivery strategies capable of providing rapid and sustained administration of multiple antagonists. Dissolving transnasal microneedles (MNs) represent a minimally invasive platform to enhance mucosal permeation; however, achieving adequate mucoadhesion while maintaining mechanical robustness remains a key formulation challenge. This work focuses on the development of mucoadhesive MN systems containing naloxone (NAL) and atipamezole (ATI) for potential field-deployable overdose intervention. Several Eudragit-based polymers, including Eudragit E PO Readymix, E PO, E 100, RS PO, and RL PO, were evaluated as candidate mucoadhesive matrices in disk and MN formats. While these systems produced structurally strong MN arrays, none demonstrated appreciable adhesion to hydrated nasal substrates. Blended formulations consisting of Eudragit (50%), polyvinylpyrrolidone (PVP, 40%), and glycerol (10%) exhibited minimal adhesion only upon hydration, suggesting that polymer charge density and hydration dynamics may limit mucosal interaction under physiological conditions. Due to limited mucoadhesion with Eudragit systems, dissolving PVP-based MN patches were fabricated as baseline formulations incorporating NAL and ATI at drug loadings of 10, 12.5, and 15 mg per patch. Although these formulations lacked intrinsic mucoadhesive properties, they maintained mechanical integrity and enabled ongoing evaluation of transnasal permeation across porcine nasal mucosa using Franz diffusion cells. Preliminary studies are currently underway to assess drug transport profiles and guide further optimization. Future work will investigate incorporation of chitosan into PVP-based MN matrices to enhance electrostatic interactions with negatively charged mucin and improve nasal residence time without compromising needle strength or dissolution behavior. Overall, these findings emphasize the complexity of balancing adhesion, mechanical performance, and drug release in transnasal MN systems and support continued formulation refinement toward rapid and sustained reversal of xylazine–opioid overdose.
Start Time
15-4-2026 9:00 AM
End Time
15-4-2026 12:00 PM
Room Number
Culp Ballroom 316
Poster Number
30
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Health
Student Type
Graduate and Professional Degree Students, Residents, Fellows
Faculty Mentor
Ashana Puri
Formulation Development of Mucoadhesive Transnasal Microneedles for Naloxone and Atipamezole Delivery Toward Xylazine–Opioid Overdose Intervention
Culp Ballroom 316
The increasing prevalence of xylazine-adulterated opioid overdoses necessitates delivery strategies capable of providing rapid and sustained administration of multiple antagonists. Dissolving transnasal microneedles (MNs) represent a minimally invasive platform to enhance mucosal permeation; however, achieving adequate mucoadhesion while maintaining mechanical robustness remains a key formulation challenge. This work focuses on the development of mucoadhesive MN systems containing naloxone (NAL) and atipamezole (ATI) for potential field-deployable overdose intervention. Several Eudragit-based polymers, including Eudragit E PO Readymix, E PO, E 100, RS PO, and RL PO, were evaluated as candidate mucoadhesive matrices in disk and MN formats. While these systems produced structurally strong MN arrays, none demonstrated appreciable adhesion to hydrated nasal substrates. Blended formulations consisting of Eudragit (50%), polyvinylpyrrolidone (PVP, 40%), and glycerol (10%) exhibited minimal adhesion only upon hydration, suggesting that polymer charge density and hydration dynamics may limit mucosal interaction under physiological conditions. Due to limited mucoadhesion with Eudragit systems, dissolving PVP-based MN patches were fabricated as baseline formulations incorporating NAL and ATI at drug loadings of 10, 12.5, and 15 mg per patch. Although these formulations lacked intrinsic mucoadhesive properties, they maintained mechanical integrity and enabled ongoing evaluation of transnasal permeation across porcine nasal mucosa using Franz diffusion cells. Preliminary studies are currently underway to assess drug transport profiles and guide further optimization. Future work will investigate incorporation of chitosan into PVP-based MN matrices to enhance electrostatic interactions with negatively charged mucin and improve nasal residence time without compromising needle strength or dissolution behavior. Overall, these findings emphasize the complexity of balancing adhesion, mechanical performance, and drug release in transnasal MN systems and support continued formulation refinement toward rapid and sustained reversal of xylazine–opioid overdose.
