Andrographolide-Soya-L-α-Phosphatidyl Choline Complex Augmented Solubility and Drug Delivery in Leishmania donovani, a Causative Agent for Cutaneous and Visceral Leishmaniasis.

Abstract

The utility of andrographolide (AN) in visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) is limited owing to poor solubility, hindered permeation, and unstable structure under physiological conditions. The present study mainly focuses on synthesizing of andrographolide-Soya-L-α-phosphatidyl choline (ANSPC) complex in ethanol and its characterization using various spectral and analytical techniques. Results from FT-IR, 1H NMR, ROSEY, and in silico docking techniques suggest ANSPC complex formation due to inter-molecular interaction between the hydrophilic head of SPC and hydroxyl group of AN present at 24th position. ANSPC complex demonstrated the solubility of 113.93 ± 6.66μg/mL significantly (P < 0.05) greater than 6.39 ± 0.47μg/mL of AN. The particle size of ANSPC complex was found to be 182.2 ± 2.69nm. The IC50 value of AN suspension (PBS, pH ~ 7.4) at 24, 48, and 72h against Leishmania donovani (L. donovani) was noticed to be 32.76 ± 4.53, 20.87 ± 2.37, and 17.71 ± 3.06μM/mL, respectively. Moreover, augmented aqueous solubility of ANSPC complex led to significant (P < 0.05) reduction in IC50 value, i.e., 25.02 ± 4.35, 11.31 ± 0.60, and 8.33 ± 2.71μM/mL at 24, 48, and 72h, respectively. The IC50 values for miltefosine were noted to be 9.84 ± 2.65, 12.13 ± 7.26, and 6.56 ± 0.61μM/mL at similar time periods. Moreover, ANSPC complex demonstrated augmented cellular uptake at 24h as compared to 6h in L. donovani. We suppose that submicron size and phospholipid-mediated complexation might have endorsed the permeation of ANSPC complex across the plasma membrane of L. donovani parasite by transport mechanisms such as P-type ATPase. ANSPC complex warrants further in-depth in vivo studies under a set of stringent parameters for translating the product into a clinically viable form.