Curcumin is one of the most promising natural therapeutics for use against Alzheimer’s disease. The major limitations of curcumin are its low oral bioavailability and difficulty in permeating the blood–brain barrier. Therefore, designing a delivery system of curcumin to overcome its limitations must be employed. KLVFF, a peptide known as an amyloid blocker, was used in this study as a targeting moiety to develop a targeted drug delivery system. A prototype of transnasal KLVFF conjugated microemulsions containing curcumin (KLVFF-Cur-ME) for the nose-to-brain delivery was fabricated. The KLVFF-Cur-ME was developed by a titration method. A conjugation of KLVFF was performed through a carbodiimide reaction, and the conjugation efficiency was confirmed by FTIR and DSC technique. KLVFD-Cur-ME was characterized for the drug content, globule size, zeta potential, and pH. A transparent and homogeneous KLVFF-Cur-ME is achieved with a drug content of 80.25% and a globule size of 76.1 ± 2.5 nm. The pH of KLVFF-Cur-ME is 5.33 ± 0.02, indicating non-irritation to nasal tissues. KLVFD-Cur-ME does not show nasal ciliotoxicity. An ex vivo diffusion study revealed that KLVFF-Cur-ME partitions the porcine nasal mucosa through diffusion, following the Higuchi model. This investigation demonstrates the successful synthesis of a bifunctional KLVFF-Cur-ME as a novel prototype to deliver anti-Aβ aggregation via an intranasal administration.

Pathological mandibular fracture after dental extraction usually occurs in dogs with moderate to severe periodontitis. A nanohydroxyapatite-based hydrogel (HAP hydrogel) was developed to diminish the limitations of hydroxyapatite for post-extraction socket preservation (PSP). However, the effect of the HAP hydrogel in dogs has still not been widely investigated. Moreover, there are few studies on PSP in dogs suffering from clinical periodontitis. The purpose of this study was to evaluate the effectiveness of the HAP hydrogel for PSP in dogs with periodontitis. In five dogs with periodontitis, the first molar (309 and 409) of each hemimandible was extracted. Consequently, all the ten sockets were filled with HAP-hydrogel. Intraoral radiography was performed on the day of operation and 2, 4, 8 and 12 weeks post operation. The Kruskal–Wallis test and paired t-test were adopted for alveolar bone regeneration analysis. The results demonstrated that the radiographic grading, bone height measurement, and bone regeneration analysis were positively significant at all follow-up times compared to the day of operation. Moreover, the scanning electron microscopy with energy-dispersive X-ray spectroscopy imaging after immersion showed a homogeneous distribution of apatite formation on the hydrogel surface. Our investigation suggested that the HAP hydrogel effectively enhances socket regeneration in dogs with periodontitis and can be applied as a bone substitute for PSP in veterinary dentistry.

Oxidative stress plays a crucial role in chronic nasal disorders, contributing to inflammation, tissue damage, and impaired mucosal function, highlighting the need for targeted therapies. Recent advancements in nasal drug delivery systems have expanded their applications for treating respiratory and inflammatory conditions. Among these, hydrogel-based systems offer prolonged release of active pharmaceutical ingredients (APIs), enhancing therapeutic efficacy and reducing dosing frequency. This study initially evaluates the antioxidant, anti-inflammatory, antimicrobial, and cytotoxic properties of Nanotriphala, followed by its incorporation into a thermoresponsive in situ hydrogel system, which was subsequently developed and characterized as a novel formulation. Nanotriphala exhibited >90% cell viability and significantly reduced nitric oxide (NO) levels by 40.55 µg/mL at 250 µg/mL. The hydrogel was characterized by key parameters, including viscosity, gelling time, pH, gelling temperature, texture analysis, and ex vivo spreadability. Stability was assessed under various conditions, and mutagenicity and antimutagenicity were evaluated using the Ames test. Results showed that the hydrogel gelled at 34 °C, exhibited good spreadability (10.25 ± 0.28 cm), a viscosity of 227 ± 22 cP, and maintained a pH of 5.75 ± 0.01, with optimal hardness and adhesiveness suitable for nasal application. It demonstrated antimicrobial activity against E. coli, P. aeruginosa, S. aureus, and S. epidermidis at minimal bactericidal concentrations (MBCs) of 32, 2, 4, and 8 µg/mL, respectively, with low mutagenicity (mutagenic index < 2) and strong antimutagenic activity (>60%). The gallic acid content was 0.5796 ± 0.0218 µg/100 mL. Stability studies confirmed optimal storage at 4 °C. These findings suggest that in situ hydrogel loaded with Nanotriphala is a promising nasal drug delivery system for managing oxidative stress and related inflammatory conditions.

Songaksorn N, et al. J Vet Sci. 2021 May;22(3):e38. https://doi.org/10.4142/jvs.2021.22.e38

Curcumin is a potent natural compound used to treat Alzheimer’s disease (AD). However, the clinical usefulness of curcumin to treat AD is restricted by its low oral bioavailability and difficulty permeating the blood-brain barrier. To overcome such drawbacks, various alternative strategies have been explored, including the transnasal route. However, rapid mucociliary clearance in the nasal cavity is a major hindrance to drug delivery. Thus, designing a delivery system for curcumin to lengthen the contact period between the drug and nasal mucosa must be employed. This study describes the optimization of KLVFF conjugated curcumin microemulsion-base hydrogel (KCMEG) to formulate a prototype transnasal preparation using the response surface method to improve a mucoadhesive property. A central composite design was employed to optimize and evaluate two influencing factors: the concentration of carbopol 940 and the percentage of KLVFF conjugated curcumin microemulsion (KCME). The physicochemical properties, anti-cholinesterase activity, and anti-aggregation activities of KCME were investigated in this study. The studied factors, in terms of main and interaction effects, significantly (p < 0.05) influenced hardness and adhesiveness. The optimized KCMEG was evaluated for pH, spreadability, and mucoadhesive properties. Ex vivo nasal ciliotoxicity to optimize KCMEG was performed through the porcine nasal mucosa. KCME was transparent, with a mean globule size of 70.8 ± 3.4 nm and a pH of 5.80 ± 0.02. The optimized KCMEG containing 2% carbopol 940 showed higher in vitro mucoadhesive potential (9.67 ± 0.13 min) compared with microemulsion and was also found to be free from nasal ciliotoxicity during histopathologic evaluation of the porcine nasal mucosa. The result revealed that both the concentration of carbopol 940 and the percentage of KCME play a crucial role in mucoadhesive properties. In conclusion, incorporating a mucoadhesive agent in a microemulsion can increase the retention time of the formulation, leading to enhanced brain delivery of the drug. Findings from the investigation revealed that KCMEG has the potential to constitute a promising approach to treating AD via transnasal administration.

This pilot study aimed to investigate the effects of gallic acid-containing mouth spray on oral microbiota in healthy cat subjects. Forty healthy cats were recruited and randomly allocated to the control (G1; n = 20) and treatment groups (G2; n = 20). The cats were treated with mouth spray twice daily for 42 days. The changes in the gingival index (GI) and plaque index (PI) were measured at baseline (day 0) and end of the study (42nd day). The changes in the oral microbial composition of representative animals (control, n = 9; and treatment, n = 8) were also evaluated at baseline and end of the study. Oral microbial composition was assessed by amplifying the V1–V3 region of the 16S rRNA gene from supragingival dental plaque DNA extracts. The sequences were annotated using the QIIME 2.0. The GI and PI were significantly reduced after 42 days of treatment. The deep sequencing revealed that mouth spray influenced the cats’ oral microbiome and was significantly diverse. About 20 phyla and 59 species were observed after 42 days of mouth spray usage in cats’ oral microbiota. The number of operational taxonomic units (OTUs) of post-treatment samples (PoTS) of G2 was greatly reduced compared to other samples. Further analysis revealed that mouth spray acts substantially against Desulfomicrobium orale, one of the known pathogens in periodontal disease. The mouth spray efficiently reduced the growth of 22 species and uprooted 17 species. Moreover, the mouth spray supported the growth of normal oral microbiota, including Moraxella and Neisseria species. The preliminary study suggested that the gallic acids-containing mouth spray could be an essential oral product to improve the oral hygiene of the cats. Moreover, further studies are needed to confirm the beneficial effect of mouth spray on cats.