TY - JOUR

T1 - Pharmacological safety of dimethoxy curcumin-human serum albumin conjugate for potential therapeutic purpose

AU - Korah, Mejo C.

AU - Harikrishnan, V. S.

AU - Deepa, S.

AU - Arya, Anil

AU - Sabareeswaran, A.

AU - Mohanan, P. V.

AU - Krishnan, Lissy K.

PY - 2023

Y1 - 2023

N2 - Medicinal properties of curcumin are widely published. Previously, researchers used curcuminoid mixture comprising three chemical forms, out of which, the highest quantity is the most active molecule-dimethoxy curcumin (DMC). Reduced bioavailability, poor aqueous solubility, and quick hydrolytic degradation of DMC have projected challenges limiting its therapeutic value. However, selective conjugation of DMC with human serum albumin (HSA) enhances drug stability and solubility by several folds. Studies using animal models demonstrated potential anti-cancer/anti-inflammatory effects of DMCHSA; both studies showed results of local administration in peritoneal cavity and rabbit knee joint. DMC has prospects as intravenous therapeutic agent because carrier is HSA. However, before in vivo testing, important preclinical data required are toxicological safety and bioavailability of soluble forms of DMC. This study evaluated absorption, distribution, metabolism, and excretion of DMCHSA. Imaging technology and molecular analysis proved bio-distribution. The study also assessed the pharmacological safety of DMCHSA in mice in terms of its acute and sub-acute toxicity, complying with regulatory toxicology. Overall, the study demonstrated the safety pharmacology of DMCHSA upon intravenous infusion. This is a novel study establishing the safety of highly soluble and stable formulation of DMCHSA, qualifying it for intravenous administration and further efficacy evaluation in suitable disease models.

AB - Medicinal properties of curcumin are widely published. Previously, researchers used curcuminoid mixture comprising three chemical forms, out of which, the highest quantity is the most active molecule-dimethoxy curcumin (DMC). Reduced bioavailability, poor aqueous solubility, and quick hydrolytic degradation of DMC have projected challenges limiting its therapeutic value. However, selective conjugation of DMC with human serum albumin (HSA) enhances drug stability and solubility by several folds. Studies using animal models demonstrated potential anti-cancer/anti-inflammatory effects of DMCHSA; both studies showed results of local administration in peritoneal cavity and rabbit knee joint. DMC has prospects as intravenous therapeutic agent because carrier is HSA. However, before in vivo testing, important preclinical data required are toxicological safety and bioavailability of soluble forms of DMC. This study evaluated absorption, distribution, metabolism, and excretion of DMCHSA. Imaging technology and molecular analysis proved bio-distribution. The study also assessed the pharmacological safety of DMCHSA in mice in terms of its acute and sub-acute toxicity, complying with regulatory toxicology. Overall, the study demonstrated the safety pharmacology of DMCHSA upon intravenous infusion. This is a novel study establishing the safety of highly soluble and stable formulation of DMCHSA, qualifying it for intravenous administration and further efficacy evaluation in suitable disease models.

KW - acute toxicity

KW - albumin-drug conjugation

KW - dimethoxy curcumin

KW - in vivo imaging

KW - repeated dose toxicity

KW - safety pharmacology

U2 - 10.1139/cjpp-2022-0408

DO - 10.1139/cjpp-2022-0408

M3 - Journal article

C2 - 36867858

AN - SCOPUS:85160965127

VL - 101

SP - 304

EP - 315

JO - Canadian Journal of Physiology and Pharmacology

JF - Canadian Journal of Physiology and Pharmacology

SN - 0008-4212

IS - 6

ER -