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Polymeric nanoparticles have demonstrated sustained and effective drug delivery in a variety of topical formulations. The aim of this project was to develop polymeric antifungal nanospheres containing terbinafine hydrochloride (TBH) to be loaded into a hydrogel formulation for topical nail drug delivery. A quality by design (QbD) approach was used to achieve optimized particles with the desired quality target product profile (QTPP). Polyvinyl alcohol (PVA) at 2% w\/v and a drug to polymer ratio of 1:4, together with a robust set of processes and material attributes, resulted in nanoparticles of 108.7 nm with a polydispersity index (PDI) of 0.63, 57.43% recovery, and other desirable characteristics such as zeta potential (ZP), particle shape, aggregation, etc. The nanospheres were incorporated into a carbomer-based gel, and the delivery of TBH through this formulation was evaluated by means of in vitro drug release testing (IVRT) and ex vivo nail permeation study. The gel containing the TBH nanospheres demonstrated a slower and controlled drug release profile compared with the control gel, in addition to a more efficient delivery into the nail. These antifungal nanospheres can be utilized for topical therapy of a multitude of superficial fungal infections.<\/jats:p>","DOI":"10.3390\/pharmaceutics14102170","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T05:31:18Z","timestamp":1665552678000},"page":"2170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Quality by Design Guided Development of Polymeric Nanospheres of Terbinafine Hydrochloride for Topical Treatment of Onychomycosis Using a Nano-Gel Formulation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3957-2378","authenticated-orcid":false,"given":"Vinam","family":"Puri","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA"},{"name":"Center for Dermal Research, Life Science Building, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-1329","authenticated-orcid":false,"given":"Anna","family":"Froelich","sequence":"additional","affiliation":[{"name":"Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parinbhai","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA"},{"name":"Center for Dermal Research, Life Science Building, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shernelle","family":"Pringle","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Graduate Studies, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA"},{"name":"Center for Dermal Research, Life Science Building, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bozena","family":"Michniak-Kohn","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA"},{"name":"Center for Dermal Research, Life Science Building, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hossain, A.S.M.M.A., Sil, B.C., Iliopoulos, F., Lever, R., Hadgraft, J., and Lane, M.E. 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