Influence of Molecular Weight on the Biological Effects of Benzocaine Modified Maleic Anhydride Copolymer

Abstract

A new series of polyanionic polymers with antitumor activity were synthesized by conjugating ethyl 4-aminobenzoate onto a series of maleic anhydride (MA) copolymers of vinyl acetate, methyl methacrylate, and styrene. The molecular weight of these copolymers ranged from 18 ϫ 10 3 to 2 ϫ 10 5 . The in vivo and in vitro biological tests showed that the maleic anhydride synthesized copolymers exhibit prolonged half-life in serum, accumulate in K 562 erythroleukemia solid tumors, and inhibit tumor growth. The antitumor activity appears to be increased by the enhanced permeability and retention (EPR) effect which is related to the macromolecular size of the antitumor agent.

Antitumoral Activity Induced by Alkylating Agents Conjugated to Poly(maleic anhydride-alt-vinyl acetate)

“…Consequently, macromolecules may accumulate in the tumor due to the vascular permeability and the decreased tissue drainage. This effect has been extensively studied and reported by Maeda [27][28][29] and recently, by Uglea [18,30]; the process is called 'enhanced permeability and retention effect' (EPR effect).…”

“…This process is influenced by several parameters, such as, the chemical structure of the monomers, molecular weight, and the ratio between the hydrophilic and hydrophobic parts of the polymer structure [18]. Consequently, the presence of bulky and hydrophobic side groups, such as the p-sulfonated anilide substituents in Conjugates I and III enhanced the EPR effect more than Conjugate II which did not have this substituent in its structure (Table 2).…”

“…In this regard, maleoyl copolymers of ampicillin, acriflavine [14,15], 4-aminobenzoic, 4-hydroxybenzoic acids, and 4-aminophenol [16,17] have provided effective conjugates. In addition, the authors have used poly(VA-alt-MA) to bind benzocaine and other heterocyclic compounds that have biologic activity [18,19]. For example, phenothiazine bound to poly(MA-alt-N-vinyl pyrrolidone) shows anti-inflammatory, antiallergenic, antibacterial, or anticancer activity [20].…”

Preparation, acidolysis kinetics and scale inhibition performance of low molecular weight poly(maleic anhydride‐alt‐vinyl acetate) based on self‐stabilized precipitation polymerization

“…Owing to the specific steric hindrance, maleic anhydride (MAH) can specifically construct alternating copolymers with vinyl acetate (VAc) with equimolar ratio of MAH to VAc in PMV chains 1 by charge transfer complex (CTC) effect. Over the past few decades, PMV has been extensively employed in the fields of biomedical, [2][3][4][5][6] blood dialysis 7 and immobilization of enzymes, 8 and so on. As the cluster luminescence of anhydride C O being discovered, 9 a series of PMV derivatives [10][11][12][13] have been researched successively.…”