International Business Machines Corporation

Agency for Science, Technology and Research

Jye Yng Teo

James L Hedrick

Yi Yan Yang

Nathaniel H Park

Chuan Yang

Xin Ding

Mu San Zhang

Robert J Ono

Julian M W Chan

Jiayu Leong

Cherylette Anne Alexander

Yiran Zhen

Jeannette M Garcia

Gregory Breyta

Alshakim Nelson

Amanda Catherine Engler

Wei Han

Daniel Joseph Coady

Willy Chin

Min-Han Tan

Shaoqiong Liu

Xiyu Ke

Yukti Choudhury

Shujun Gao

Techniques regarding a chemical composition that can be utilized within one or more combination therapies to treat a microbial infection are provided. For example, one or more embodiments described herein can comprise a chemical composition that includes a first triblock polymer comprising a quaternary ammonium functionalized polycarbonate block and exhibiting anticancer activity via a lytic mechanism. The chemical composition can also include a second triblock polymer comprising a guanidinium functionalized polycarbonate block and exhibiting anticancer activity via a translocation mechanism.

Combination therapies that enhance antimicrobial/anticancer activities

Amphiphilic block copolymers (BCPs) were prepared comprising a poly(ethylene oxide) block and a biodegradable polycarbonate block functionalized with disulfide groups and carboxylic acid groups. The BCPs form self-assembled micellar particles in aqueous solution that can be loaded with hydrophobic drugs for therapeutic drug delivery. The loaded particles have small particle sizes (&#x3c;100 nm), narrow particle size distributions, and high drug loading capacity (up to about 50 wt %) based on total dry weight of the loaded particles. Particles loaded with DOX released the DOX in response to changes in pH and glutathione (GSH) redox chemistry. The loaded particles efficiently delivered and released DOX within tumor cells, effectively suppressing growth of the tumor cells at a similar or even lower drug concentration than free DOX. Blank particles containing no DOX did not induce cytotoxicity to cells.

Block copolymers for therapeutic drug delivery

Cationic antimicrobial polymers have been synthesized by a bulk addition polymerization of a nucleophilic agent comprising two tertiary amines and an electrophilic agent that comprises two leaving groups and an aromatic ring between the leaving groups. The reaction solvent for the polymerization is chosen to allow precipitation of the cationic polymer at the polymerization temperature, thereby limiting molecular weight. Quaternization and polymerization occur concurrently. The cationic polymers can be highly active against Gram-negative and Gram-positive microbes, and/or fungi. The cationic polymers can also be non-hemolytic and non-cytotoxic at the effective concentration against the microbes.

Antimicrobial polymers formed by bulk polyaddition

A number of cationic antimicrobial polymers have been synthesized by a condensation polymerization in bulk. The initial polymer formed has backbone tertiary nitrogens, which are subsequently quaternized using a suitable quaternizing agent (e.g., alkyl halide). The cationic polymers include polyamides, polycarbonates, polypolyureas and polyguanidiniums having a cationic repeat unit comprising the quaternary ammonium nitrogen as a backbone nitrogen. The cationic polymers can be active against Gram-negative, Gram-positive microbes, and/or fungi.

Condensation polymers for antimicrobial applications

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Jye Yng Teo