International Business Machines Corporation

Agency for Science, Technology and Research

Coral Bay Ii, Llc.

Institute of Bioengineering and Nanotechnology, Biomedical Sciences Institute

Willy Chin

James L Hedrick

Yi Yan Yang

Dylan J Boday

Rudy J Wojtecki

Jeannette M Garcia

Ashlynn L Z Lee

Robert J Ono

Qingxing Xu

Zhi Xiang Voo

Xiyu Ke

Nathaniel H Park

Mareva B Fevre

Victoria A Piunova

Noah F Fine Nathel

Nor Lizawati Ibrahim

Eunice Leong

Amanda Catherine Engler

Daniel Joseph Coady

Victor W L Ng

Min-Han Tan

Shrinivas Venkataraman

Jye Yng Teo

Zhan-Yuin Ong

Yukti Choudhury

Eunice Leong Jiayu

Shujun Gao

Techniques regarding star polymers with enhanced antimicrobial functionality are provided. For example, a polymer is provided that can comprise a core that can have a singlet oxygen generator and that can generate a singlet oxygen species upon irradiation with light. The polymer can also comprise a plurality of polycarbonate arms covalently bonded to the core. The plurality of polycarbonate arms can be degradable and can comprise a cation. Further, the plurality of polycarbonate arms can have antimicrobial functionality.

Star polymers with enhanced antimicrobial activity in response to light

Antimicrobial cationic polycarbonates and polyurethanes have been prepared comprising one or more pendent guanidinium and/or isothiouronium groups. Additionally, antimicrobial particles were prepared having a silica core linked to surface groups comprising a guanidinium and/or isothiouronium group. The cationic polymers and cationic particles can be potent antimicrobial agents against Gram-negative microbes, Gram-positive microbes, and/or fungi.

Antimicrobial guanidinium and thiouronium functionalized polymers

Polythioaminal polymers are made from hexahydrotriazine precursors and dithiol precursors. The precursors are blended together and subjected to mild heating to make the polymers. The polymers have the general structure wherein each Ris independently an organic or hetero-organic group, each Ris independently a substituent having molecular weight no more than about 120 Daltons, X and Z are each a sulfur-bonded species, at least one of X and Z is not hydrogen, and n is an integer greater than or equal to 1. X and Z may be hydrogen or a functional group, such as a thiol-reactive group. The reactive thiol groups of the polythioaminal may be used to attach thiol-reactive end capping species. By using water soluble or water degradable dithiols, such as polyether dithiols, water soluble polythioaminals may be made. Some such polymers may be used to deliver therapeutics with non-toxic aqueous degradation products.

Method of making sulfur-containing polymers from hexahydrotriazine and dithiol precursors

The subject matter of this invention relates to block copolymers (BCPs) and, more particularly, to block copolymers capable of self-assembly into nanoparticles for the delivery of hydrophobic cargos. The BCPs include a hydrophobic block that contains a thioether functional group that is susceptible to oxidation, transforming the solubility of the block from hydrophobic to hydrophilic, thereby releasing the hydrophobic cargo of the nanoparticle.

Block copolymers and self-assembling nanoparticles formed therefrom

The present disclosure relates to polythioaminals with applications as carriers or delivery vehicles for therapeutic agents or other small molecule cargo. Polythioaminal block copolymer coupled to a therapeutic agent is a polymer-therapeutic conjugate that exhibits higher stability and longer life time in aqueous environments. The polythioaminal block copolymer coupled to a therapeutic agent can be synthesized by reacting hexahydrotriazines with a hydrophobic block precursor, a hydrophilic block precursor, a particle stabilizing segment precursor, and a cargo, such as a therapeutic agent, in a one pot synthesis. The ease of synthesizing the resulting polythioaminal block copolymer coupled to the therapeutic agent while offering the extended stability and polymer life time in aqueous environments make the polythioaminal block copolymer particularly attractive for therapeutic carriers.

Preparation of robust polythioaminal carriers

Sulfur-containing polymers from hexahydrotriazine and dithiol precursors as a carrier for active agents

Antimicrobial cationic polymers having one or two cationic polycarbonate chains were prepared by organocatalyzed ring opening polymerization. One antimicrobial cationic polymer has a polymer chain consisting essentially of cationic carbonate repeat units linked to one or two end groups. The end groups can comprise a covalently bound form of biologically active compound such as cholesterol. Other antimicrobial cationic polymers have a random copolycarbonate chain comprising a minor mole fraction of hydrophobic repeat units bearing a covalently bound form of a vitamin E and/or vitamin D2. The cationic polymers exhibit high activity and selectivity against Gram-negative and Gram-positive microbes and fungi.

Antimicrobial cationic polycarbonates

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

Growing community of inventors

Singapore, Singapore

Willy Chin