Behrad Yadolahi, Mehdi Taghian, Leyli Sadri
Advanced polymeric drug delivery systems, particularly electrospun nanofibers and mucoadhesive patches, are promising platforms for the local treatment of periodontal and oral mucosal diseases. However, evidence regarding fabrication reproducibility, mucosal interactions, therapeutic efficacy, and stability has not been systematically synthesized. This systematic review evaluated novel polymeric carriers for dental and oral applications, with emphasis on fabrication parameters, drug loading, mucoadhesion, release behavior, immunomodulatory effects, clinical outcomes, and safety. Following PRISMA guidelines and the PICO framework, two independent reviewers searched PubMed, Scopus, Web of Science, the Cochrane Library, and Google Scholar for English-language studies published between 2015 and 2025. Eligible studies investigated novel polymeric carriers, primarily electrospun or composite systems, and reported fabrication parameters, including polymer type, preparation method, and drug loading, along with relevant biological or clinical outcomes. Risk of bias was assessed using SYRCLE/OHAT tools for original studies and AMSTAR-2 for review articles. Eight studies (four original research studies and four review articles) met the inclusion criteria. The included studies evaluated polymers, such as PLA/nano-HAP, chitosan/PVA/PCL, and PLLA/PEO, in combination with active agents including doxycycline, neem extract, curcumin, diclofenac sodium, and binahong extract. Electrospinning consistently generated porous, uniform carriers with fiber diameters of approximately 250-500 nm, sustained release ranging from 82% over 8 h to 60-80% over 7 days, mucoadhesive strength up to 0.34 N, immunomodulatory effects reflected by reduced IL-1, TNF-α, and MMP-8 levels, and antibacterial efficacy up to 98%. These systems also maintained mucosa-compatible pH values (6.5-7.0) and showed no evidence of irritation or toxicity. Needleless electrospinning variants further improved scalability. However, heterogeneity in fabrication parameters and moderate overall risk of bias, mainly from review-based evidence, limited direct comparisons across studies. Overall, electrospun nanofibers and mucoadhesive patches demonstrated promising potential as biocompatible platforms for targeted local drug delivery in dentistry, with the capacity to enhance immunomodulatory and antimicrobial effects in periodontitis, aphthous stomatitis, and oral ulcers. Further studies incorporating standardized fabrication validation and long-term stability testing are recommended to support clinical translation.