Discipline: Chemistry and Chemical Sciences
Subcategory: Chemistry (not Biochemistry)
Michael Arocho - University of Puerto Rico at Aguadilla
Co-Author(s): Rahul K. Keswani and Gus R. Rosania, University of Michigan - College of Pharmacy, Ann Arbor, MI
Clofazimine (CFZ), a weak basic lipophilic drug, is an FDAapproved leprostatic (interferes with proliferation of the bacterium that causes leprosy, Mycobacterium leprae) antibiotic and anti-inflammatory drug. CFZ drug massively accumulates in macrophages forming an insoluble intracellular crystal-like drug inclusions (CLDIs) during long-term oral dosing. Based on previous investigations, the main cellular effect of CLDIs is that macrophages acquire a more anti-inflammatory, wound-healing phenotype. The many interesting chemical, physical, and biological properties of CLDIs could serve as a starting point for developing new kinds of CFZ-based solid-state nanoderivatives with potential applications in diagnostics, drug delivery, and therapeutics. Therefore, is very important to study the physicochemical properties and the surface properties of CFZ crystals. That way we also understand the interactions of CLDIs with the cell as a first point contact. Accordingly, we hypothesized that CFZ crystals have hydrophilic and/or hydrophobic surfaces. To study the surface characteristics of the lipophilic drug crystal, we used polymeric microspheres (plain polystyrene and surface modified with COOH and NH2 group) to identify surface interaction patterns with CFZ crystals and probe surface hydrophilicity. The results revealed that there was more binding to the pointed edges (0.06) of CFZ-HCl relative to long edges (0.01) by the COOH microspheres with a (0.06/0.01=) 6fold difference in the binding. In addition, our data show that there was more binding by the NH2 (0.03) and plain (0.02) microspheres to the long edges of CFZ-HCl crystals relative to the long edges (0.01) by the COOH microspheres with a (0.03/0.01=) 3-fold and (0.02/0.01=) 2-fold difference in the binding. Whereas the interactions of the microspheres in CLDIs, it is not that different amongst the samples. Differences in binding of polystyrene microspheres CLDIs and CFZ-HCl crystals suggest different surface structures leading to different interface interactions.
Funder Acknowledgement(s): NSF - National Science Foundation; University of Michigan - College of Pharmacy
Faculty Advisor: Gus Rosania,