Influence of Melanin Characteristics on Drug Binding Properties

Abstract

Melanins are biopolymers encompassing a high degree of chemical heterogeneity. Binding of small-molecule drugs to ocular melanin significantly affects the ocular pharmacokinetics, and could serve as a strategy for prolonged drug retention in the eye. The influence of the structural and physical characteristics of melanins originating from different sources on their drug binding properties has not yet been methodically investigated. We performed physical characterization of Sepia officinalis, synthetic and porcine melanin. The particle size distribution was analyzed by laser diffractometry. A dynamic vapor sorption method, requiring small amounts of the material, was developed to analyze the differences in the specific surface area of the melanins. The extent of melanin binding at equilibrium was determined for a set of 34 small-molecule drugs and compared across different melanin types. Despite systematic shifts in the extent of binding within a twofold range, binding data were highly correlated across the melanins. These moderate differences in binding could not be directly explained by the substantial differences in particle size and were more in line with the relatively similar specific surface area of these different melanin materials. Overall, these results suggest that the specific surface area reflects the actual accessibility of a small molecule in the melanin structure and could serve as a surrogate to explain the binding differences observed for the respective melanin materials.

Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs

“…Overall, the preparation of melanin nanoparticles was crucial for the use of MST, because aggregation and adsorption were seen with unmodified synthetic and isolated melanin (porcine RPE [ 9 ]; data not shown). Furthermore, the previous work of Jakubiak et al [ 36 ] showed correlation among the drug binding to different melanin types (porcine RPE-choroid, sepia, and synthetic), supporting the notion that melanin binding is a robust phenomenon over melanin from different sources.…”

Melanin, the What, the Why and the How: An Introductory Review for Materials Scientists Interested in Flexible and Versatile Polymers

“…Similar to its ability to bind ions, melanin is known to bind and accumulate drugs within its structure, with this property known since at least the 1960s. For examples, see references [39,[114][115][116][117][118][119][120].…”

Rutin Exerts Cytotoxic and Senescence-Inducing Properties in Human Melanoma Cells

“…Melanin is a negatively charged biopolymer that colors various human structures such as skin, hair, and eyes [ 38 ]. The main biological function of melanin is to exert a cytoprotective effect against noxious UV radiations by serving as a physical barrier and absorbent filter that reduces their penetration through the epidermis [ 39 ], as well as against oxidative stress damage by scavenging free radicals [ 40 ]. Hence, melanin can bind small molecules, leading to their retention in the pigmented tissues [ 40 ] followed by a slow release of the accumulated toxins [ 37 ].…”

“…The main biological function of melanin is to exert a cytoprotective effect against noxious UV radiations by serving as a physical barrier and absorbent filter that reduces their penetration through the epidermis [ 39 ], as well as against oxidative stress damage by scavenging free radicals [ 40 ]. Hence, melanin can bind small molecules, leading to their retention in the pigmented tissues [ 40 ] followed by a slow release of the accumulated toxins [ 37 ]. In particular, melanin interacts by hydrogen and π−π bonding with small aromatic molecules [ 40 ] such as RUT.…”