Issara Sramala

Water-soluble β-cyclodextrin grafted with chitosan and its inclusion complex as a mucoadhesive eugenol carrier

Inclusion complex between water-soluble βCD-grafted chitosan derivatives (QCD-g-CS) and eugenol (EG) was investigated as a new type of mucoadhesive drug carrier. The QCD-g-CSs were synthesized with various βCD moieties ranging from 5 to 23%. Spontaneous inclusion complex of these derivatives and EG were found and confirmed by FTIR and simulation study. Self-aggregated formations of QCD-g-CS were found, according to fluorescence and TEM studies, where the formations were preferable for QCD11g-CS and QCD5-g-CS. EG can be included in both βCD hydrophobic cavity and hydrophobic core of QCD-g-CS self-aggregates, resulting in varying entrapment efficiencies. Degree of QCD substitution on QCD-g-CS plays an important role on their physical properties, due to steric hindrance. The QCD11-g-CS showed excellent mucoadhesion, compared to the QCD5-g-CS and QCD23-g-CS. Moreover, the inclusion complex between QCD-g-CS and EG tend to express higher antimicrobial activities against Candida albicans, Streptococcus oralis and Streptococcus mutans, than the native QCD-g-CS.

Self-aggregates formation and mucoadhesive property of water-soluble β-cyclodextrin grafted with chitosan.

Water-soluble β-cyclodextrin grafted with chitosan (CD-g-CS) was carried out by quaternizing the CD-g-CS with glycidyltrimethyl ammonium chloride (GTMAC) under mild acidic condition, corresponding to the quaternized CD-g-CS (QCD-g-CS). The degrees of substitution (DS) and quaternization (DQ), ranging from 5% to 23% and 66% to 80%, respectively, were determined by (1)H NMR spectroscopy. Self-aggregates formation of all QCD-g-CSs were investigated in water using dynamic light scattering (DLS), atomic force microscopy (AFM), and transmission electron microscopy (TEM) techniques. The result revealed that all QCD-g-CSs are able to form self-aggregates in water. Large particle sizes ranged from 800 to 3000nm were obtained by DLS while zeta-potentials were ranging from 25 to 40mV. AFM and TEM depicted a spherical shape with particle sizes ranging from 100 to 900nm. Mucoadhesive and cytotoxic properties of all QCD-g-CSs were evaluated using a mucin particle method and MTT assay compared to quaternized chitosan (QCS). It was found that the mucoadhesive property increased with decreasing DS due to less quaternary ammonium moiety into the chitosan backbone. On the other hand, the cytotoxicity increased with increasing DS even though the DQ is decreased.

A comparison of spacer on water-soluble cyclodextrin grafted chitosan inclusion complex as carrier of eugenol to mucosae

In this study two types of water-soluble βCD grafted chitosan were synthesized and compared based on similar degree of N-substitution of βCD moiety; QCD23-g-CS contained methylene spacer and QCDCA22-g-CS contained citric acid spacer. The QCD23-g-CS demonstrated greater eugenol (EG) encapsulation efficiency than that of QCDCA22-g-CS. The micelle-like assemblies of QCD23-g-CS led to slower release of EG while it did not observe in case of QCDCA22-g-CS. It was found that EG could absorb on chitosan backbone according to in silico modeling. Cytotoxicity of both derivatives against buccal mucosa cell is concentration-dependent. The QCDCA22-g-CS demonstrated stronger mucoadhesive response than that of QCD23-g-CS, due to hydrogen bonding according to mucin particle and SPR methods. Our results revealed that the spacer on both derivatives played an important role on binding affinity with EG, releasing profile and mucoadhesive property. These derivatives could be considered as promising carriers for mucosal delivery system.

Encapsulation of Citral Isomers in Extracted Lemongrass Oil with Cyclodextrins: Molecular Modeling and Physicochemical Characterizations

The complexation between two isomers of citral in lemongrass oil and varying types of cyclodextrins (CDs), α-CD, β-CD, and HP-β-CD, were studied by molecular modeling and physicochemical characterization. The results obtained revealed that the most favorable complex formation governing between citrals in lemongrass oil and CDs were found at a 1:2 mole ratio for all CDs. Complex formation between E-citral and CD was more favorable than between Z-citral and CD. The thermal stability of the inclusion complex was observed compared to the citral in the lemongrass oil. The release time course of citral from the inclusion complex was the diffusion control, and it correlated well with Avrami’s equation. The release rate constants of the E- and Z-citral inclusion complexes at 50 °C, 50% RH were observed at 1.32×10−2 h−1 and 1.43×10−2 h−1 respectively.

A comparison of eugenol and menthol on encapsulation characteristics with water-soluble quaternized β-cyclodextrin grafted chitosan

Two guest molecules (eugenol and (-)-menthol) were investigated on inclusion complex formation with water-soluble quaternized β-CD grafted with chitosan (QCD-g-CS). The inclusion complexes were prepared at varying mole ratios between eugenol or (-)-menthol and β-CD (substituted on QCD-g-CS) by a conventional shaking method and obtained as solid powder by freeze-drying process. The results showed that encapsulation efficiency %EE decreased with increasing of initial eugenol or (-)-menthol loading whereas %loading increased with increasing of initial eugenol or (-)-menthol loading. The results indicated that inclusion complex formation between eugenol and QCD-g-CS was more favorable than that of (-)-menthol. To clarify this mechanism, molecular dynamics simulations were performed to explore their binding energy, solvation energy and total free energy of those complexes. It was found that the total free energy (ΔG) of eugenol and (-)-menthol against QCD-g-CS (mole ratio of 1) in water-explicit system were -2108.91 kJ/mol and -344.45 kJ/mol, respectively. Moreover, molecular dynamic simulation of eugenol absorbed on surface QCD-g-CS (-205.73 kJ/mol) was shown to have a higher negative value than that of (-)-menthol on QCD-gCS (3182.31 kJ/mol). Furthermore, the release characteristics of the encapsulated powder were also investigated in simulated saliva pH 6.8 at 32 °C. The results suggested that (-)-menthol had higher release rate from the complexes than eugenol. In all cases, the release characteristics for those guest molecules could be characterized by the limited-diffusion kinetics.

Enhanced stability and in vitro bioactivity of surfactant-loaded liposomes containing Asiatic Pennywort extract

The objective of this work has been the microencapsulation of Asiatic Pennywort (AP) extract with lecithin from soybean. The effect of various quantities of non-ionic surfactant (Montanov82®) on liposomes upon physicochemical characteristics as well as their in vitro bio-activities was investigated. An addition of surfactant resulted in a decrease in particle size and an increase in percentage AP entrapment efficiency of liposomes. The surfactant-loaded liposomes demonstrated higher stability than surfactant-free liposomes where higher percentage AP remaining of liposomes can be achieved depending on surfactant concentration. No significant difference was found on AP release profiles among varied surfactant concentrations, although a presence of surfactant resulted in prolonged AP release rate. Liposomal AP with 20% w/w surfactant or higher demonstrated low cytotoxicity, a stronger anti-oxidation effect and collagen production on dermal fibroblast cells when compared with free AP and surfactant-free liposomes, possibly due to better cell internalization and less AP degradation in cells.

Development of an in Vitro System to Simulate the Adsorption of Self-Emulsifying Tea (Camellia oleifera) Seed Oil

In this study, tea (Camellia oleifera) seed oil was formulated into self-emulsifying oil formulations (SEOF) to enhance the aqueous dispersibility and intestinal retention to achieve higher bioavailability. Self-emulsifying tea seed oils were developed by using different concentrations of lecithin in combination with surfactant blends (Span®80 and Tween®80). The lecithin/surfactant systems were able to provide clear and stable liquid formulations. The SEOF were investigated for physicochemical properties including appearance, emulsion droplets size, PDI and zeta potential. The chemical compositions of tea seed oil and SEOF were compared using GC-MS techniques. In addition, the oil adsorption measurement on artificial membranes was performed using a Franz cell apparatus and colorimetric analysis. The microscopic structure of membranes was observed with scanning electron microscopy (SEM). After aqueous dilution with fed-state simulated gastric fluid (FeSSGF), the droplet size of all SEOF was close to 200 nm with low PDI values and the zeta potential was negative. GC-MS chromatograms revealed that the chemical compositions of SEOF were not significantly different from that of the original tea seed oil. The morphological study showed that only the SEOF could form film layers. The oil droplets were extracted both from membrane treated with tea seed oil and the SEOF in order to evaluate the chemical compositions by GC-MS.

Improved anti-dust mite properties of textiles by eugenol loaded chitosan nanoparticles

Recently polymeric nanoparticles have been widely explored as a carrier for a wide application including drug delivery. Eugenol loaded chitosan nanoparticles were prepared by ionic gelation method between cationic chitosan and anionic tripolyphosphate (TPP). The size and eugenol entrapment efficiency of prepared nanoparticles were strongly dependent on molecular weight of chitosan, degree of deacetylation of chitosan, weight ratio between chitosan and TPP and % loading of eugenol. The nanoparticles coated cotton fabric demonstrated activity against dust mite viability, indicating improved anti-dust mite properties of textile materials.

Synthesis and characterization of ²-cyclodextrin-grafted chitosan derivatives on its mucoadhesion and antibacterial activities

The aims of this study were to synthesize and determine the biological activities of two types of water-soluble βCD-grafted chitosan derivatives; βCD-grafted chitosan with spacer (QCDCA22-g-CS) and βCD-grafted chitosan without spacer (QCD23-g-CS) as a novel biomaterial for mucosal delivery. Difference in their chemical structure were defined by 1H-NMR According to mucin particle method, QCD23-g-CS showed stronger mucoadhesion towards mucin. Although both QCDCA22-g-CS and QCD23-g-CS demonstrated high antibacterial activity towards Candida albicans at 24 hours, QCD23-g-CS demonstrated much higher activity than QCDCA22-g-CS.