Co-encapsulated Apigenin and Clove Oil in Nanostructured Lipid Carriers for Enhanced Periodontal Disease Therapy

Ashfaq, Rabia and Kovács, Anita and Berkó, Szilvia and Katona, Gábor and Paróczai, Dóra and Szécsényi, Mária and Burián, Katalin and Vályi, Péter and Veres, Katalin and Girst, Gábor and Hunyadi, Attila and Polgár, Tamás Ferenc and Budai-Szűcs, Mária (2026) Co-encapsulated Apigenin and Clove Oil in Nanostructured Lipid Carriers for Enhanced Periodontal Disease Therapy. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 115. No. 107644. ISSN 1773-2247

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Abstract

Periodontitis is a chronic inflammatory disease that compromises the integrity of the periodontal tissues and affects tooth retention. This study introduces a localized treatment strategy using nanostructured lipid carriers (NLCs) co-loaded with apigenin (AP) and clove oil (CO) to enhance antibacterial, anti-inflammatory, and antioxidant efficacy. The CO-loaded optimized nanoformulation, developed via Box–Behnken design, exhibited a particle size of 196.4 nm, polydispersity index of 0.24, zeta potential of − 19.5 mV, high entrapment efficiency (90.6 %), and reduced crystallinity index (14.06 %). The crystallinity index, systematically evaluated during the optimization process, provided insights into the behavior of the lipid matrix, release rate, and long-term performance. Following this optimization, AP was incorporated into the NLCs, and the resulting formulation underwent further evaluation. Morphological analysis confirmed the nanorange smooth surface and well-dispersed particles. Antioxidant activity, assessed via DPPH and ORAC assays, improved significantly with nanoencapsulation. In vitro testing on LPS-stimulated MRC-5 fibroblasts showed downregulation of COX-2, IL-1β, and IL-6, confirming strong anti-inflammatory potential. MTT assay indicated ≥80 % cell viability, demonstrating good cytocompatibility. Antimicrobial studies demonstrated the enhanced efficacy of co-loaded NLCs against Aggregatibacter actinomycetemcomitans and Streptococcus mutans, with synergistic effects (FIC <0.5) and reduced MIC/MBC values compared to single-loaded active agents. This co-encapsulation approach presents a promising, multifunctional nanosystem for targeted periodontal therapy, offering enhanced stability, improved bioactivity, and reduced systemic toxicity.

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