PREPARATION AND CHARACTERIZATION OF MODIFIED COLORED RICE AS A GELLING CARRIER FOR BUCCAL DRUG DELIVERY SYSTEM

Objective: The present study was to prepare and characterize the chemically modified rice from the colored rice grains as a gelling agent for buccal gel preparation.Methods: The colored rice grains from two different varieties, Homnil (HN) and Kum-Doisket (KD), were compared. The chemically modified rice was prepared by etherification. The obtained modified samples were investigated for their solid structure using scanning electron microscope and X-ray diffractometer. The solubility and swelling property in water were also investigated. Rice gel bases and drug loading gels were prepared by hydration and levigation methods, respectively. The obtained gels were evaluated for rheological, adhesive, and drug release properties.Results: The HN and KD rice varieties yielded modified rice powders with different morphology, crystallinity, aqueous solubility, and swelling characteristics. The amylose content in different rice variety significantly affected the internal crystalline structure of the rice powders and adhesive as well as rheological properties of the respectively derived gels. Rheological behavior of the colored rice gels was pseudoplastic non-Newtonian flow. The drug release property of HN and KD gels was influenced by swelling property of the gel base. Different gel properties reflected the different rice varieties used for gel preparation.Conclusion: The variety of rice can affect the properties of the gelling agent from colored rice grains. The chemical modified colored rice grain can be feasible to be the good gelling agents in Pharmaceutical buccal gel preparation.Keyword: Rice variety, Rice gel, buccal gel, Amylose content, Carbamide peroxid

ANTIFUNGAL EFFECT OF HYPTIS SUAVEOLENS OIL MICROEMULSION BASED CARBOXYMETHYL MUNGBEAN GEL FOR TOPICAL DELIVERY

Objective: Conventional topical antifungal formulations limit the effectiveness of antifungal therapy. The aim of this study was to formulate effective antifungal microemulsion of H. suaveolens oil based carboxymethyl mungbean (CMMS) gel.Methods: H. suaveolens oil was obtained by steam distillation. Standard of H. suaveolens oil was performed by gas chromatography mass spectrometry (GC/MS). A high-viscosity CMMS was prepared and its mucoadhesive property was determined using modified USP dissolution test apparatus. H. suaveolens oil microemulsion based CMMS gel as transdermal drug carrier was then developed. Finally, in vitro drug release study and antifungal activity were determined.Results: GC/MS analysis exhibited that b-Caryophyllene, Sabinene and Limonene are the major components of H. suaveolens oil. CMMS gel revealed good mucoadhesive potential which depended on pH of the medium. A higher retention time in pH 4.5 medium than pH 10 medium was observed. Clotrimazole-loaded H. suaveolens oil microemulsions based CMMS gel was successful prepared and in vitro sustained release of clotrimazole was determined. Clotrimazole-loaded H. suaveolens oil microemulsions based CMMS gel had potent antifungal activity against all studied dermatophytes and Candida albican with higher inhibition zone than H. suaveolens oil microemulsions based CMMS gel, H. suaveolens oil and commercial clotrimazole cream.Conclusion: H. suaveolens oil microemulsions based CMMS gel present promising as an effective alternative for topical delivery of antifungal agents.Â

Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells.

BackgroundWilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compound from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, WT1 protein and mRNA stability, and cell proliferation in K562 cell line.MethodsM. siamensis seeds were obtained from the region of Chiang Mai (North of Thailand). Mammea E/BB was extracted from seeds of M. siamensis. WT1 protein expression and stability were evaluated by Western blot analysis. WT1 mRNA stability was assessed by qRT-PCR. WT1-DNA binding and WT1 promoter activity were assayed by ChIP assay and luciferase-reporter assay, respectively. Cell cycle arrest was studied by flow cytometry.ResultsTreatment with mammea E/BB led to down-regulation of WT1 expression. The suppression of WT1 expression did not involve protein and mRNA degradation. Rather, WT1 protein was down-regulated through disruption of transcriptional auto-regulation of the WT1 gene. Mammea E/BB inhibited WT1-DNA binding at the WT1 promoter and decreased luciferase activity. It also disrupted c-Fos/AP-1 binding to the WT1 promoter via ERK1/2 signaling pathway and induced S phase cell cycle arrest in K562 cells.ConclusionMammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation

Preparation of Lipid Nanoemulsions Incorporating Curcumin for Cancer Therapy

The aim of this study was to develop a new formulation of a curcumin lipid nanoemulsion having the smallest particle size, the highest loading, and a good physical stability for cancer chemotherapy. Curcumin lipid nanoemulsions were prepared by a modified thin-film hydration method followed by sonication. Soybean oil, hydrogenated L-α-phosphatidylcholine from egg yolk, and cosurfactants were used to formulate the emulsions. The resultant nanoemulsions showed mean particle diameter of 47–55 nm, could incorporate 23–28 mg curcumin per 30 mL, and were stable in particle size for 60 days at 4°C. The cytotoxicity studies of curucumin solution and curcumin-loaded nanoemulsion using B16F10 and leukemic cell lines showed IC50 values ranging from 3.5 to 30.1 and 22.2 to 53.7 μM, respectively. These results demonstrated the successful incorporation of curcumin into lipid nanoemulsion particles with small particle size, high loading capacity, good physical stability, and preserved cytotoxicity

ANTI-INFLAMMATORY, ANTIBACTERIAL, AND ANTIOXIDANT ACTIVITIES OF THAI MEDICINAL PLANTS

Objective: Acacia farnesiana (L.) Willd, Senna alata (L.) Roxb., Sesbania grandiflora (L.) Pers., Syzygium cumini (L.) Skeels and Tabernaemontana divaricate (L.) R. Br. ex Roem. & Schult. are used in Thai traditional remedies to treat various disorders ranging from fever and pain to inflammation or microbial infections. However, there is a lack of scientific data on some of the biological activities. Methods: The present study was designed to compare the antibacterial, antioxidant, and anti-inflammatory effects of the five plants. Ethanolic extracts of A. farnesiana, S. alata, S. grandiflora, S. cumini, T. divaricata were firstly compared for antioxidant activity using free radical scavenging of 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power tests. Antibacterial activity indicated by minimum bactericidal concentration (MBC) was determined using broth and agar dilution tests against aerobic and anaerobic pathogenic bacterial strains. The anti-inflammatory activity was evaluated in vitro using a lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage model.Results: All the tested extracts exerted antioxidant, antibacterial and anti-inflammatory effects. S. cumini and S. grandiflora extracts showed the highest free radical scavenging activities. S. cumini extract showed the highest activity against Staphylococcus aureus, S. epidermidis, and Corynebacterium diphtheriae. All extracts exerted anti-inflammatory activity as indicated by a reduction of interleukin (IL)-6 secretion and/or tumor necrosis factor (TNF)-α production.Conclusion: Taken together, these findings suggest that the tested plants can be developed as effective herbal remedies for the treatment and prevention of inflammation or associated diseases as well as against bacterial infections.Â

BIOACTIVITIES OF THE THAI MEDICINAL AND EDIBLE PLANTS C. CAJAN, M. CITRIFOLIA AND O. AMERICANUM

Objective: Inflammation and oxidative stress are closely related and play a role in various diseases. If an infectious component plays a role, an antibacterial effect is of advantage. Thus, natural remedies which combine different bioactivities have a broader range of application.Methods: Here we elucidate the anti-inflammatory, antioxidant and antibacterial effects of three edible and traditionally used Thai plants including leaves of Cajanus cajan, Morinda citrifolia and Ocimum americanum.Results: The extracts exerted significant anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated macrophages. C. cajan extract shows a broad spectrum of antibacterial activity against Gram positive and negative, aerobic and anaerobic bacteria, whereas M. citrifolia and O. americanum possess antibacterial activity only against anaerobic bacteria. Extracts of all three plants showed significant antioxidant effects.Conclusion: The three plants are potential herbal remedies or supplements for functional food for the treatment and prevention of inflammation, oxidative imbalance, and bacterial infections or associated diseases.Â

LFA-1 on Leukemic Cells as a Target for Therapy or Drug Delivery

Leukemia therapeutics are aiming for improved efficacy by targeting molecular markers differentially expressed on cancerous cells. Lymphocyte function-associated antigen-1 (LFA-1) expression on various types of leukemia has been well studied. Here, the role and expression of LFA-1 on leukemic cells and the possibility of using this integrin as a target for drug delivery is reviewed. To support this rationale, experimental results were also included where cIBR, a cyclic peptide derived from a binding site of LFA-1, was conjugated to the surface of polymeric nanoparticles and used as a targeting ligand. These studies revealed a correlation of LFA-1 expression level on leukemic cell lines and binding and internalization of cIBR-NPs suggesting a differential binding and internalization of cIBR-NPs to leukemic cells overexpressing LFA-1. Nanoparticles conjugated with a cyclic peptide against an accessible molecular marker of disease hold promise as a selective drug delivery system for leukemia treatment

Doxorubicin-Loaded Polymeric Micelles Conjugated with CKR- and EVQ-FLT3 Peptides for Cytotoxicity in Leukemic Stem Cells

Doxorubicin (Dox) is the standard chemotherapeutic agent for acute myeloblastic leukemia (AML) treatment. However, 40% of Dox-treated AML cases relapsed due to the presence of leukemic stem cells (LSCs). Thus, poloxamer 407 and CKR- and EVQ-FLT3 peptides were used to formulate Dox-micelles (DMs) and DM conjugated with peptides (CKR and EVQ) for improving AML-LSC treatment. Results indicated that DMs with a weight ratio of Dox to P407 of 1:200 had a particle size of 23.3 ± 1.3 nm with a high percentage of Dox entrapment. They were able to prolong drug release and maintain physicochemical stability. Following effective DM preparation, P407 was modified and conjugated with FLT3 peptides, CKR and EVQ to formulate DM-CKR, DM-EVQ, and DM-CKR+DM-EVQ. Freshly synthesized DMs displaying FLT3 peptides showed particle sizes smaller than 50 nm and a high drug entrapment level, comparable with DMs. DM-CKR+DM-EVQ was considerably more toxic to KG-1a (AML LSC-like cell model) than Dox-HCl. These FLT3-targeted DMs could increase drug uptake and induce apoptosis induction. Due to an increase in micelle-LSC binding and uptake, DMs displaying both peptides tended to improve the potency of Dox compared to a single peptide-coupled micelle

Antibacterial and Antioxidant Activities of Acid and Bile Resistant Strains of Lactobacillus fermentum Isolated from Miang

Miang is a kind of traditional fermented tea leaves, widely consumed in northern Thailand as a snack. It contains several kinds of Lactobacilli spp. The aim of this study was to isolate strains of Lactobacillus fermentum from miang and to investigate their antibacterial and antioxidant activities. The agar spot and well assays were used for determination of antibacterial power. The antibacterial mechanism was investigated by cell morphologic change under scanning electron microscope (SEM). Antioxidant activity was studied by means of free radical scavenging and ferric reducing power assays. The acid and bile screening tests indicated that L. fermentum FTL2311 and L. fermentum FTL10BR presented antibacterial activity against several pathogenic bacteria: Listeria monocytogenes DMST 17303, Salmonella Typhi DMST 5784, Shigella sonnei DMST 561 (ATCC 11060)and Staphylococcus aureus subsp. aureus DMST 6512 (ATCC 6538Ptm). The results from SEM suggested that the antibacterial action was due to the destruction of cell membrane which consequently caused the pathogenic cell shrinking or cracking. The antioxidant study suggested that both L. fermentum FTL2311 and L. fermentum FTL10BR strains could liberate certain substances that possessed antioxidant activity expressed as trolox equivalent antioxidant capacity (TEAC) and equivalent concentration (EC) values for free radical scavenging and reducing mechanisms, respectively. The supernatant of L. fermentum FTL2311 broth revealed TEAC and EC values of 22.54±0.12 and 20.63±0.17 µM.mg-1 respectively, whereas that of L. fermentum FTL10BR yielded TEAC and EC values of 24.09±0.12 and 21.26±0.17 µM.mg-1 respectively. These two strains isolated from miang present high potential as promising health-promoting probiotics

Enhancement of Cholinesterase Inhibition of Alpinia galanga (L.) Willd. Essential Oil by Microemulsions

This study aimed to investigate the chemical composition and reveal the selective inhibitory activity of Alpinia galanga (L.) Willd. essential oil (AGO) on acetylcholinesterase (AChE) compared to butyrylcholinesterase (BChE). The chemical composition of AGO was investigated by means of gas chromatography–mass spectrometry. Ellman’s method was used to determine the inhibitory activities against AChE and BChE. Microemulsion systems with desirable anticholinesterase effects were developed. Methyl cinnamate and 1,8-cineole were reported as the major component of AGO. The IC50 values of A. galanga oil against AChE and BChE were 24.6 ± 9.6 and 825.4 ± 340.1 µg/mL, respectively. The superior selectivity of AGO on AChE (34.8 ± 8.9) compared to galantamine hydrobromide (6.4 ± 1.5) suggested AGO to be an effective ingredient with fewer side effects for Alzheimer’s treatment. Interestingly, the microemulsion of AGO possessed significantly higher anticholinesterase activity than that of native oil alone. Therefore, microemulsion of AGO is a promising alternative approach for the treatment of Alzheimer’s disease