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Item Clindamycin-modified Triple Antibiotic Nanofibers: A Stain-free Antimicrobial Intracanal Drug Delivery System(Elsevier, 2018-01) Karczewski, Ashley; Feitosa, Sabrina A.; Hamer, Ethan I.; Pankajakshan, Divya; Gregory, Richard L.; Spolnik, Kenneth J.; Bottino, Marco C.; Biomedical Sciences and Comprehensive Care, School of DentistryINTRODUCTION: A biocompatible strategy to promote bacterial eradication within the root canal system after pulpal necrosis of immature permanent teeth is critical to the success of regenerative endodontic procedures. This study sought to synthesize clindamycin-modified triple antibiotic (metronidazole, ciprofloxacin, and clindamycin [CLIN]) polymer (polydioxanone [PDS]) nanofibers and determine in vitro their antimicrobial properties, cell compatibility, and dentin discoloration. METHODS: CLIN-only and triple antibiotic CLIN-modified (CLIN-m, minocycline-free) nanofibers were processed via electrospinning. Scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and tensile testing were performed to investigate fiber morphology, antibiotic incorporation, and mechanical strength, respectively. Antimicrobial properties of CLIN-only and CLIN-m nanofibers were assessed against several bacterial species by direct nanofiber/bacteria contact and over time based on aliquot collection up to 21 days. Cytocompatibility was measured against human dental pulp stem cells. Dentin discoloration upon nanofiber exposure was qualitatively recorded over time. The data were statistically analyzed (P < .05). RESULTS: The mean fiber diameter of CLIN-containing nanofibers ranged between 352 ± 128 nm and 349 ± 128 nm and was significantly smaller than PDS fibers. FTIR analysis confirmed the presence of antibiotics in the nanofibers. Hydrated CLIN-m nanofibers showed similar tensile strength to antibiotic-free (PDS) nanofibers. All CLIN-containing nanofibers and aliquots demonstrated pronounced antimicrobial activity against all bacteria. Antibiotic-containing aliquots led to a slight reduction in dental pulp stem cell viability but were not considered toxic. No visible dentin discoloration upon CLIN-containing nanofiber exposure was observed. CONCLUSIONS: Collectively, based on the remarkable antimicrobial effects, cell-friendly, and stain-free properties, our data suggest that CLIN-m triple antibiotic nanofibers might be a viable alternative to minocycline-based antibiotic pastes.Item Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug(Springer, 2022) Stein Gold, Linda; Baldwin, Hilary; Kircik, Leon H.; Weiss, Jonathan S.; Pariser, David M.; Callender, Valerie; Lain, Edward; Gold, Michael; Beer, Kenneth; Draelos, Zoe; Sadick, Neil; Pillai, Radhakrishnan; Bhatt, Varsha; Tanghetti, Emil A.; Dermatology, School of MedicineBackground: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. Objectives: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. Methods: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. Results: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. Conclusions: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne.