Nanocarrier-Integrated Topical Dosage Forms for Biofilm-Infected Wounds: Balancing Wound Retention, Biofilm Matrix Penetration, and Translational Feasibility.

Abstract

Biofilm-infected wounds are difficult to treat because extracellular polymeric substance (EPS) matrices, wound exudate, polymicrobial spatial organization, impaired antimicrobial penetration, persistent inflammation, and antimicrobial tolerance limit the efficacy of conventional topical therapy. Nanocarriers can protect antimicrobial payloads, enable controlled and stimuli-responsive release, and improve interactions with biofilm matrices; however, their clinical performance also depends on the final topical dosage form that governs wound residence, local exposure, usability, and translation. This review critically examines nanocarrier-integrated topical dosage forms for biofilm-infected wounds by linking nanoscale carrier design with macroscale platform performance. Hydrogels and in situ gels, films, membranes, wound dressings, nanofibers, sprays, foams, and multifunctional systems are discussed in relation to wound retention, exudate management, EPS access, and controlled antimicrobial release. Key strategies, including pH-, enzyme-, ROS-, and light-responsive delivery, EPS disruption, matrix penetration, photothermal and photodynamic therapy, ion-mediated killing, quorum-sensing interference, and wound-adaptive regenerative support, are integrated with translational considerations such as polymicrobial biofilm models, cytocompatibility, recurrence prevention, sterilization, storage stability, manufacturing scalability, regulatory classification, and patient-centered usability. By bridging nanocarrier engineering with topical dosage-form design, this review provides a formulation-oriented roadmap for clinically feasible antibiofilm nanomedicine for chronic and infected wounds, supporting control of infectious diseases, healthcare innovation, and sustainable manufacturing considerations.