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Nanoparticulate assembly of mannuronic acid- and guluronic acid-rich alginate: oral insulin carrier and glucose binder

Kadir A, Mokhtar MT, Wong TW

J Pharm Sci, 2013 Dec;102(12):4353-63.
PMID: 24258282 DOI: 10.1002/jps.23742

The relationship of high and low molecular weight mannuronic acid (M)- and guluronic acid (G)-rich alginate nanoparticles as oral insulin carrier was elucidated. Nanoparticles were prepared through ionotropic gelation using Ca(2+) , and then in vitro physicochemical attributes and in vivo antidiabetic characteristics were examined. The alginate nanoparticles had insulin release retarded when the matrices had high alginate-to-insulin ratio or strong alginate-insulin interaction via OH moiety. High molecular weight M-rich alginate nanoparticles were characterized by assemblies of long polymer chains that enabled insulin encapsulation with weaker polymer-drug interaction than nanoparticles prepared from other alginate grades. They were able to encapsulate and yet release and have insulin absorbed into systemic circulation, thereby lowering rat blood glucose. High molecular weight G- and low molecular weight M-rich alginate nanoparticles showed remarkable polymer-insulin interaction. This retarded the drug release and negated its absorption. Blood glucose lowering was, however, demonstrated in vivo with insulin-free matrices of these nanoparticles because of the strong alginate-glucose binding that led to intestinal glucose retention. Alginate nanoparticles can be used as oral insulin carrier or glucose binder in the treatment of diabetes as a function of its chemical composition. High molecular weight M-rich alginate nanoparticles are a suitable vehicle for future development into oral insulin carrier.
Blood glucose lowering property of water in oral insulin-fed diabetic rats

Wong TW, Sumiran N, Mokhtar MT, Kadir A

Pharm Biol, 2012 Nov;50(11):1463-6.
PMID: 22889006 DOI: 10.3109/13880209.2012.679985

In oral insulin delivery, blood glucose profiles of a subject can be a function of complicated transfer of water and insulin between gastrointestinal and blood compartments.
Fulltext Genotoxicity following Organophosphate Pesticides Exposure among Orang Asli Children Living in an Agricultural Island in Kuala Langat, Selangor, Malaysia

Sutris JM, How V, Sumeri SA, Muhammad M, Sardi D, Mohd Mokhtar MT, et al.

Int J Occup Environ Med, 2016 Jan;7(1):42-51.
PMID: 26772597 DOI: 10.15171/ijoem.2016.705

BACKGROUND: Agriculture is an important sector for the Malaysian economy. The use of pesticides in agriculture is crucial due to its function in keeping the crops from harmful insects. Children living near agricultural fields are at risk of pesticide poisoning.
OBJECTIVE: To evaluate the genotoxic risk among children who exposed to pesticides and measure DNA damage due to pesticides exposure.
METHODS: In a cross-sectional study 180 Orang Asli Mah Meri children aged between 7 and 12 years were studied. They were all living in an agricultural island in Kuala Langat, Selangor, Malaysia. The data for this study were collected via modified validated questionnaire and food frequency questionnaire, which consisted of 131 food items. 6 urinary organophosphate metabolites were used as biomarkers for pesticides exposure. For genotoxic risk or genetic damage assessment, the level of DNA damage from exfoliated buccal mucosa cells was measured using the comet assay electrophoresis method.
RESULTS: Out of 180 respondents, 84 (46.7%) showed positive traces of organophosphate metabolites in their urine. Children with detectable urinary pesticide had a longer tail length (median 43.5; IQR 30.9 to 68.1 μm) than those with undetectable urinary pesticides (median 24.7; IQR 9.5 to 48.1 μm). There was a significant association between the extent of DNA damage and the children's age, length of residence in the area, pesticides detection, and frequency of apple consumption.
CONCLUSION: The organophosphate genotoxicity among children is associated with the amount of exposure (detectability of urinary pesticide) and length of residence in (exposure) the study area.

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