Thermoresponsive Azithromycin-Loaded Niosome Gel Based on Poloxamer 407 and Hyaluronic Interactions for Periodontitis Treatment.

Azithromycin (AZM) is a potential antimicrobial drug for periodontitis treatment. However, a potential sustained-release system is needed for intra-periodontal pocket delivery. This study focused on the development and evaluation of a thermoresponsive azithromycin-loaded niosome gel (AZG) to search for a desirable formulation for periodontitis treatment. AZG was further developed from an AZM-loaded niosomal formulation by exploiting the advantages of poloxamer 407 (P407) and hyaluronic acid (HA) interactions. The results showed that the addition of HA decreased the gelation temperature and gelation time of AZG. HA was found to increase the viscosity as well as mucoadhesive and tooth-root surface adhesive properties. The AZG solution state was injectable and exhibited pseudoplastic shear-thinning behavior. P407-HA interactions in AZG could contribute to gel strength. AZG showed 72 h of continuous drug release following the Korsmeyer-Peppas model and potentially enhanced drug permeation. The formulations apparently presented more efficient antibacterial activity against major periodontal pathogens than the standard AZM solution. AZM intra-periodontal pocket formulation and the remarkable properties of niosomes exhibited potential characteristics, including ease of administration, bioadhesion to the anatomical structure of the periodontal pocket, and sustained drug release with competent antimicrobial activity, which could be beneficial for periodontitis treatment.

Polymeric Micelles Enhance Mucosal Contact Time and Deposition of Fluocinolone Acetonide.

This study used polymeric micelles to improve quality by increasing drug solubility, extending mucosal drug retention time, enhancing mucoadhesiveness, and promoting drug permeation and deposition. Fluocinolone acetonide (FA) was loaded into polymeric micelles (FPM), which were composed of poloxamer 407 (P407), sodium polyacrylate (SPA), and polyethylene glycol 400, and their physicochemical properties were examined. Small-angle X-ray scattering (SAXS) revealed a hexagonal micellar structure at all temperatures, and the concentrations of P407 and SPA were shown to significantly affect the solubility, mucoadhesion, release, and permeation of FPMs. The proportion of P407 to PEG at a ratio of 7.5:15 with or without 0.1% w/v of SPA provided suitable FPM formulations. Moreover, the characteristics of FPMs revealed crystalline states inside the micelles, which was consistent with the morphology and nano-hexagonal structure. The results of ex vivo experiments using focal plane array (FPA)-based Fourier transform infrared (FTIR) imaging showed that the FPM with SPA penetrated quickly through the epithelium, lamina propria, and submucosa, and remained in all layers from 5-30 min following administration. In contrast, the FPM without SPA penetrated and passed through all layers. The FPM with extended mucoadhesion, improved drug-mucosal retention time, and increased FA permeation and deposition were successfully developed, and could be a promising innovation for increasing the efficiency of mouth rinses, as well as other topical pharmaceutical and dental applications.

Efficacy and safety of two artificial saliva-based polymers containing 0.1% pilocarpine for treatment of xerostomia: A randomized clinical pilot trial.

BACKGROUND: Topical agents are the mainstay in the treatment of xerostomia, a common complaint most frequently associated with salivary dysfunction. This study aimed to compared the efficacy and safety for xerostomia treatment of 2 artificial saliva preparations containing 0.1% pilocarpine, and, either sodium carboxymethylcellulose (SCMC), or, sodium polyacrylate (SPA). MATERIAL AND METHODS: Thirty-one xerostomia patients were randomly allocated into either a SCMC-treated group (15 patients), or, a SPA-treated group (16 patients). The formulations were taken 0.5 ml, 4 times daily for 6 weeks and double-blinded assessed before and after treatments using Xerostomia Inventory (XI) and Clinical Oral Dryness Score (CODs). Unstimulated and stimulated whole salivary flow rates were measured. RESULTS: After treatment, the SCMC-treated group had significantly lower CODs and higher unstimulated and stimulated whole salivary flow rates (p<0.001, p=0.035, and p=0.013, respectively), while the SPA-treated group showed significantly lower CODs only (p=0.004). In contrast, SCMC-treated and SPA-treated groups at the 6th week after treatments showed non-significant differences in all assessments (p>0.05, all). Some adverse events (AEs) were reported, e.g., burning tongue, dizziness and watery eyes, but no severe AEs. CONCLUSIONS: This randomized controlled pilot trial demonstrated superior efficacy of SCMC-formula over a SPA-formula after 6 weeks of xerostomia treatment. These formulations with topical pilocarpine proved safe in clinical use with minimal reported AE. Key words:Xerostomia, artificial saliva, sodium carboxymethylcellulose, sodium polyacrylate, pilocarpine.

Formulation development and evaluation of lidocaine hydrochloride loaded in chitosan-pectin-hyaluronic acid polyelectrolyte complex for dry socket treatment.

The main purpose of this study was to assess a lidocaine hydrochloride-loaded chitosan-pectin-hyaluronic polyelectrolyte complex for rapid onset and sustained release in dry socket wound treatment. Nine formulations (LCs) of lidocaine hydrochloride (LH) loaded into a chitosan-pectin-hyaluronic polyelectrolyte complex (PEC) were assessed using full factorial design (two factors × three levels). The formulations ranged between 4 and 10% w/w LH and 0.5-1.5% w/w HA. The following physicochemical properties of LCs were characterized: size, zeta potential, % entrapment efficiency, viscosity, mucoadhesiveness, % drug release, morphology, storage stability, and cytotoxicity. The particle size, zeta potential, % EE, viscosity, and % mucoadhesion increased with increasing LH and HA concentrations. Rapid release of LH followed a zero-order model, and a steady-state percentage of the drug was released over 4 h. LCs were found to be non-cytotoxic compared to LH solution. LH loaded into PEC demonstrated appropriate characteristics-including suitable rate of release-and fit a zero-order model. Furthermore, it was not cytotoxic and showed good stability in a high-HA formula, making it a promising candidate for future topical oral formulations.

Anthocyanin complex niosome gel accelerates oral wound healing: In vitro and clinical studies.

An anthocyanin complex (AC), composed of extracts of purple waxy corn and blue butterfly pea petals, and AC niosomes, bilayered vesicles of non-ionic surfactants, were compared in in vitro and clinical studies. Cultured fibroblasts subjected to a scratch wound were monitored for cell viability, cell migration, nuclear morphology and protein expression. Scratched cells showed accelerated wound healing activity, returning to normal 24 h after treatment with AC niosomes (0.002 mg/mL). Western blots and immunocytochemistry indicated upregulation of type I, III and IV collagens, fibronectin and laminins in AC niosome-treated scratched cells. A randomized block placebo-controlled double-blind clinical trial in 60 volunteers (18-60 years old) with oral wounds indicated that AC niosome gel accelerated wound closure, reduced pain due to the oral wounds and improved participants' quality of life more than AC gel, triamcinolone gel and placebo gel. These data are consistent with enhanced delivery of AC to fibroblasts by use of niosomes. AC niosomes activated fibroblasts within wounded regions and accelerated wound healing, indicating that AC niosomes have therapeutic potential.

Topical oral wound healing potential of anthocyanin complex: animal and clinical studies.

AIM: An anthocyanin complex (AC), combined Zea mays and Clitoria ternatea extracts, was evaluated for topical oral wound healing in rats and a clinical trial in orthodontic patients. METHODS/RESULTS: AC enhanced anthocyanin permeation in vitro. In rats, 10% w/w of AC in a mucoadhesive gel (AG) reduced erythema and sizes of oral wounds after topical applications at higher extent than its placebo gel. Acute orthodontic wounds in 68 volunteers were randomly assigned to topically receive either AG or placebo gel and double-blind assessed. Wound size reduction and wound closure enhancement were obvious in AG-treated group on day 3 (p < 0.05). CONCLUSION: At 10% w/w, AC promoted wound closure and possessed a potential in healing stimulation of acute oral wounds.

Topical Niosome Gel Containing an Anthocyanin Complex: a Potential Oral Wound Healing in Rats.

Anthocyanins from dietary sources showing potential benefits as anti-inflammatory in oral lesions were developed as an anthocyanin complex (AC), comprised of extracts of Zea mays (CC) and Clitoria ternatea (CT), and formulated into a niosome gel to prove its topical oral wound healing in vitro and in vivo investigations. The AC formed nano-sized clusters of crystalline-like aggregates, occurring through both intra- and inter-molecular interactions, resulting in delivery depots of anthocyanins, following encapsulation in niosomes and incorporation into a mucoadhesive gel. In vitro permeation of anthocyanins was improved by complexation and further enhanced by encapsulation in niosomes. Collagen production in human gingival fibroblasts was promoted by AC and AC niosomes, but not CC or CT. The in vivo wound healing properties of AC gel (1 and 10%), AC niosome gel (1 and 10%), fluocinolone acetonide gel, and placebo gel were investigated for incisional wounds in the buccal cavities of Wistar rats. AC gel and AC niosome gel both reduced wound sizes after 3 days. AC niosome gel (10%) gave the highest reduction in wound sizes after day 3 (compared to fluocinolone acetonide gel, p < 0.05), and resulted in 100% wound healing by day 5. Histological observations of cross-sectioned wound tissues revealed the adverse effects of fluocinolone gel and wound healing potential of AC niosome gel. Topical application of AC niosome gel exhibited an anti-inflammatory effect and promoted oral wound closure in rats, possibly due to the improved mucosal permeability and presence of delivery depots of AC in the niosome gel.

Intranasal melatonin nanoniosomes: pharmacokinetic, pharmacodynamics and toxicity studies.

AIM: Intranasal melatonin encapsulated in nanosized niosomes was preclinically evaluated. METHODOLOGY: A formula of melatonin niosomes (MN) was selected through physicochemical and cytotoxic data for pharmacokinetic, pharmacodynamics and toxicity studies in male Wistar rats. RESULTS: Intranasal MN was bioequivalent to intravenous injection of melatonin, providing therapeutic level doses. Acute and subchronic toxicity screening showed no abnormal signs, symptoms or hematological effects in any animals. Transient nasal irritations with no inflammation were observed with intranasal MN, leading it to be categorized as relatively harmless. CONCLUSION: The intranasal MN could deliver melatonin to the brain to induce sleep and provide delayed systemic circulation, relative to intravenous injection and also distribute to peripheral tissue.