International Business Machines Corporation

Agency for Science, Technology and Research

Universidad Del París Vasco/euskal Herriko Unibertsitatea

Victor W L Ng

James L Hedrick

Yi Yan Yang

Ashlynn L Z Lee

Amanda Catherine Engler

Daniel Joseph Coady

Zhan-Yuin Ong

Mareva B Fevre

Richard Anthony Dipietro

Robert J Ono

Jeremy P K Tan

Shrinivas Venkataraman

Chuan Yang

Wei Cheng

Willy Chin

Zhi Xiang Voo

Julian M W Chan

Xiyu Ke

Haritz Sardon

Nor Lizawati Ibrahim

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

Gel-forming block copolymers were prepared comprising i) a central hydrophilic block consisting essentially of a divalent poly(ethylene oxide) chain and ii) two peripheral monocarbonate or polycarbonate hydrophobic blocks linked to the central block by linking groups bearing one or more hydrogen bond forming *&#x2014;N(H)&#x2014;* groups. The hydrophobic blocks comprise one or more vitamin-bearing subunits. The gel-forming block copolymers can be used to prepare various biodegradable and/or biocompatible hydrogel and organogel drug compositions, in particular antimicrobial and/or anti-tumor drug compositions. The hydrogel compositions have utility in depot injections for drug delivery. The hydrogen bonding *&#x2014;N(H)&#x2014;* group(s) provide longer in vivo lifetime of the hydrogel before degradation and a more prolonged and controlled release rate of a hydrophobic drug compared to similar hydrogels prepared from poly(ethylene glycol).

Vitamin functionalized gel-forming block copolymers for biomedical applications

Eight-membered ring cyclic carbonates having an oxygen or an acylated nitrogen at position 6 were prepared by reaction of precursor diols with ethyl chloroformate. The cyclic carbonates undergo organocatalyzed ring opening polymerization. In one instance, the initial polymer formed comprises a carbonate repeat unit having a Boc-protected nitrogen in the polymer backbone. Deprotecting the nitrogen with acid forms a cationic carbonate repeat unit having a positive charged secondary ammonium nitrogen in the polymer backbone.

Cyclic carbonate monomers and ring opened polycarbonates therefrom

Nanoparticles comprise a drug, a first block polymer and a second block polymer. The first block polymer has a poly(ethylene oxide) (PEO) block and a polycarbonate block bearing a side chain aromatic nitrogen-containing heterocycle (N-heterocycle). The N-heterocycle can be in the form of a base, a hydrosalt of the base, a sulfobetaine adduct of the base, or a combination thereof. The second block polymer has a PEO block and a polycarbonate block bearing a side chain catechol group, which can be present as a catechol, oxidized form of a catechol, and/or a polymerized form of a catechol. The nanoparticles can be dispersed in water and are capable of controlled release of the drug.

Polycarbonates bearing aromatic N-heterocycles for drug delivery

Gel-forming block copolymers were prepared comprising i) a central hydrophilic block consisting essentially of a divalent poly(ethylene oxide) chain and ii) two peripheral monocarbonate or polycarbonate hydrophobic blocks. The hydrophobic blocks comprise one or more vitamin-bearing subunits. The vitamin-bearing subunits comprise a carbonate backbone portion and a side chain comprising a covalently bound form of a vitamin. The gel-forming block copolymers can be used to prepare various biodegradable and/or biocompatible hydrogel and organogel drug compositions, in particular antimicrobial and/or anti-tumor drug compositions. The hydrogel compositions can be suitable for depot injections. Synergistic enhancement of toxicity to microbes was observed with compositions comprising an antimicrobial cationic polymer and an antimicrobial compound.

Growing community of inventors

Singapore, Singapore

Victor W L Ng