Tags

Type your tag names separated by a space and hit enter

Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs.
Pharmaceutics. 2020 Jun 16; 12(6)P

Abstract

Interactions between drugs and melanin pigment may have major impacts on pharmacokinetics. Therefore, melanin binding can modify the efficacy and toxicity of medications in ophthalmic and other disease of pigmented tissues, such as melanoma. As melanin is present in many pigmented tissues in the human body, investigation of pigment binding is relevant in drug discovery and development. Conventionally, melanin binding assays have been performed using an equilibrium binding study followed by chemical analytics, such as LC/MS. This approach is laborious, relatively slow, and limited to facilities with high performance quantitation instrumentation. We present here a screening of melanin binding with label-free microscale thermophoresis (MST) that utilizes the natural autofluorescence of melanin. We determined equilibrium dissociation constants (Kd) of 11 model compounds with melanin nanoparticles. MST categorized the compounds into extreme (chloroquine, penicillin G), high (papaverine, levofloxacin, terazosin), intermediate (timolol, nadolol, quinidine, propranolol), and low melanin binders (atropine, methotrexate, diclofenac) and displayed good correlation with binding parameter values obtained with the conventional binding study and LC/MS analytics. Further, correlation was seen between predicted melanin binding in human retinal pigment epithelium and choroid (RPE-choroid) and Kd values obtained with MST. This method represents a useful and fast approach for classification of compounds regarding melanin binding. Thus, the method can be utilized in various fields, including drug discovery, pharmacokinetics, and toxicology.

Authors+Show Affiliations

School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland.School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland.Drug Research Programme, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland.Drug Research Programme, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland.School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland.School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland. Drug Research Programme, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland. Laboratory of Biohybrid Technologies, Institute of Chemistry, St. Petersburg State University, Peterhoff, St. Petersburg 198504, Russia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32560065

Citation

Hellinen, Laura, et al. "Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs." Pharmaceutics, vol. 12, no. 6, 2020.
Hellinen L, Bahrpeyma S, Rimpelä AK, et al. Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs. Pharmaceutics. 2020;12(6).
Hellinen, L., Bahrpeyma, S., Rimpelä, A. K., Hagström, M., Reinisalo, M., & Urtti, A. (2020). Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs. Pharmaceutics, 12(6). https://doi.org/10.3390/pharmaceutics12060554
Hellinen L, et al. Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs. Pharmaceutics. 2020 Jun 16;12(6) PubMed PMID: 32560065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs. AU - Hellinen,Laura, AU - Bahrpeyma,Sina, AU - Rimpelä,Anna-Kaisa, AU - Hagström,Marja, AU - Reinisalo,Mika, AU - Urtti,Arto, Y1 - 2020/06/16/ PY - 2020/05/21/received PY - 2020/06/10/revised PY - 2020/06/11/accepted PY - 2020/6/21/entrez PY - 2020/6/21/pubmed PY - 2020/6/21/medline KW - drug delivery KW - eye KW - melanin KW - microscale thermophoresis KW - pigment KW - pigment-binding KW - retina KW - screening KW - targeting JF - Pharmaceutics JO - Pharmaceutics VL - 12 IS - 6 N2 - Interactions between drugs and melanin pigment may have major impacts on pharmacokinetics. Therefore, melanin binding can modify the efficacy and toxicity of medications in ophthalmic and other disease of pigmented tissues, such as melanoma. As melanin is present in many pigmented tissues in the human body, investigation of pigment binding is relevant in drug discovery and development. Conventionally, melanin binding assays have been performed using an equilibrium binding study followed by chemical analytics, such as LC/MS. This approach is laborious, relatively slow, and limited to facilities with high performance quantitation instrumentation. We present here a screening of melanin binding with label-free microscale thermophoresis (MST) that utilizes the natural autofluorescence of melanin. We determined equilibrium dissociation constants (Kd) of 11 model compounds with melanin nanoparticles. MST categorized the compounds into extreme (chloroquine, penicillin G), high (papaverine, levofloxacin, terazosin), intermediate (timolol, nadolol, quinidine, propranolol), and low melanin binders (atropine, methotrexate, diclofenac) and displayed good correlation with binding parameter values obtained with the conventional binding study and LC/MS analytics. Further, correlation was seen between predicted melanin binding in human retinal pigment epithelium and choroid (RPE-choroid) and Kd values obtained with MST. This method represents a useful and fast approach for classification of compounds regarding melanin binding. Thus, the method can be utilized in various fields, including drug discovery, pharmacokinetics, and toxicology. SN - 1999-4923 UR - https://www.unboundmedicine.com/medline/citation/32560065/Microscale_Thermophoresis_as_a_Screening_Tool_to_Predict_Melanin_Binding_of_Drugs L2 - https://www.mdpi.com/resolver?pii=pharmaceutics12060554 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.