ABSTRACT
Chitosan or polyvinyl pyrrolidone (PVP) were used in combination with hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407) as gelling agents for oral drug delivery. The performance interaction with mucin of chitosan-composed gel (F1) and PVP-composed gel (F2) was compared using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy at controlled temperatures of 25 and 37 °C for 1 and 5 min. F1 containing niosome-entrapped melatonin or its derivatives was investigated for mucoadhesive interaction on mucosa by ATR-FTIR spectroscopy under the same conditions. The results showed that F1-treated mucin gave a significantly lower amide I/amide II ratio than untreated mucin and F2-treated mucin did within 1 min, suggesting improved rapid affinity between mucin and chitosan. The spectra of mucosa treated with F1 incorporating niosomes of melatonin or its derivatives showed peak shifts at C=O (amide I), N-H (amide II), and carbohydrate regions and an associated decrease in the amide I/amide II ratio and increase in the carbohydrate/amide II ratio. These results indicated electrostatic interaction and hydrogen bonding between chitosan and mucin on the mucosa. In conclusion, the molecular interaction between gels and mucin/mucosa detected at amide I and amide II of proteins and the carbohydrate region could lead to an improved mucoadhesive property of the gel on the mucosa.
ABSTRACT
AIM: A transmucosal niosome gel was developed to improve the pharmacokinetics of exogenous melatonin. MATERIALS & METHODS: The melatonin niosomes (MN) gel was characterized and melatonin levels were determined in healthy volunteers. RESULTS: Micron-sized MN in a gel, mean ex vivo residence time of more than 3 h with maximum adhesiveness at 25 and 37°C showed similar in vitro release but different in vitro permeation to melatonin gel. Oral transmucosal MN gels, at 2.5, 5 and 10 mg, topically applied in 14 healthy volunteers in a randomized double-blinded crossover design with 7-day washout, gave dose-proportional pharmacokinetics, with improved absorption and prolonged systemic circulation. CONCLUSION: The transmucosal MN gel provides a topical option for melatonin administration with substantial prolonged systemic delivery.
Subject(s)
Melatonin/administration & dosage , Sleep Aids, Pharmaceutical/administration & dosage , Sleep/drug effects , Administration, Mucosal , Adult , Animals , Cross-Over Studies , Esophageal Mucosa/metabolism , Gels , Healthy Volunteers , Humans , Liposomes , Male , Melatonin/pharmacokinetics , Oral Mucosal Absorption , Prospective Studies , Sleep Aids, Pharmaceutical/pharmacology , Swine , Young AdultABSTRACT
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.
