2,4-Dichlorophenoxy Acetic Acid as an Antidiabetic Drug: In silico, Preformulation and in vivo Approaches

Abstract:

Background: 2,4-Dichlorophenoxy acetic acid (2,4-D) was recently rediscovered as new anti-inflammatory agent through an in silico molecular modeling and in vivo anti-inflammatory inspection. Further computational investigations showed very close similarity between 2,4-D and pioglitazone in the mode of binding to PPAR_γ ligand binding pocket, suggesting an antidiabetic activity. Aim: To evaluate the binding strength of 2,4-D to PPAR_γ binding pocket and to improve the low water solubility of 2,4-D in formulation. Methods: particle size reduction via Nano Spray Dryer B-90 was chosen as possible technique to enhance the drug solubility and in turn facilitating its formulation. Chemical and physical properties of both raw and micronized forms of 2,4-D were investigated utilizing FTIR and DSC respectively. Additionally, dissolution profiles in different dissolution media were evaluated. Finally, the antidiabetic activity of micronized 2,4-D was investigated using streptozotocin (STZ)-induced animal model. Results: Revealed enhanced dissolution profiles for the micronized form of the drug on all media under investigation compared to its raw form. The in vivo antidiabetic activity for micronized 2,4-D form indicated no significant difference in its blood sugar lowering activity compared to pioglitazone as reference drug. Conclusion: the previous results could suggest micronized 2,4-D as a cheap antidiabetic agent with similar activity to pioglitazone.

Key words: 2,4-D, Micronized, Pioglitazone, Repositioning, Streptozotocin.