4.7 Article

Encapsulating melittin from animal venom by finely tuned charge compensation with polymer carriers

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EUROPEAN POLYMER JOURNAL
卷 190, 期 -, 页码 -

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.eurpolymj.2023.111996

关键词

Melittin; Encapsulation; Polyanion; Block copolymer

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This paper presents an efficient platform for forming polypeptide complexes from cationic amphiphilic animal venoms, such as melittin. The platform utilizes supramolecular charge compensation between melittin and nanoparticles composed of hydrophobic glassy polystyrene core and hydrophilic poly(meth)acrylic acid corona. The study demonstrates the successful complexation of melittin with nanoparticles at low concentrations and discusses the influence of nanoparticle structures on their potency.
Due to their wide availability, polypeptide/protein venoms produced by certain insects are of high interest as potential active pharmacological ingredients; however, the number of clinical studies on these venoms remains poor. In this paper, we describe an extremely efficient platform to form polyplexes from cationic amphiphilic animal venoms, such as the hemolytic poison melittin. The idea is based on supramolecular melittin cationic charge compensation with nanoparticles (micelles composed of hydrophobic glassy polystyrene core and hy-drophilic poly(meth)acrylic acid corona, PMA and PAA acid homopolymers) with high anion charge density at physiological pH. An instant mix and go process and efficient melittin complexation with nanoparticles at concentrations down to micrograms per milliliter of PBS solution was achieved and proven by inhibition of melittin-induced hemolysis. We studied in detail how the structural features of the nanoparticles influence their potency; we found that the most important parameter is the number of carboxylates in the polyanion chain (proportional to the molecular weight and length of the anionic poly(meth)acrylic acid block). The poly(meth) acrylic acid-based polymer nanoparticles may be useful as melittin (and possibly other cationic amphiphilic animal venoms) antidotes but also as models for constructing future delivery systems to apply the venoms therapeutically.

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