4.8 Article

Highly Effective and Safe Polymeric Inhibitors of Herpes Simplex Virus in Vitro and in Vivo

Journal

ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 30, Pages 26745-26752

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b10302

Keywords

herpes simplex virus; polymeric inhibitors; PEG(x)-b-PMAPTAC(y); antiviral activity; polymer cell membrane interaction; in vitro and in vivo experiments

Funding

  1. National Science Center, Poland [UMO-2014/13/B/ST5/04510, UMO-2012/07/E/NZ6/01712]
  2. Ministry of Science and Higher Education

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A series of poly(ethylene glycol)-block-poly(3(-methacryloylamino)propyl trimethylammonium chloride) (PEG-b-PMAPTAC) water-soluble block copolymers consisting of PEG and PMPTAC were obtained by reversible addition-fragmentation chain transfer (RAFT) polymerization and demonstrated to function as highly effective herpes simplex virus type 1 (HSV-1) inhibitors as shown by in vitro tests (Vero E6 cells) and in vivo experiments (mouse model). Half maximal inhibitory concentration (IC50) values were determined by quantitative polymerase chain reaction to be 0.36 +/- 0.08 mu g/mL for the most effective polymer PEG(45)-b-PMAPTAC(52) and 0.84 +/- 1.24 mu g/mL for the less effective one, PEG(45)-b-PMAPTAC(74). The study performed on the mouse model showed that the polymers protect mice from lethal infection. The polymers are not toxic to the primary human skin fibroblast cells up to the concentration of 100 mu g/mL and to the Vero E6 cells up to 500 mu g/mL. No systemic or topical toxicity was observed in vivo, even with mice treated with concentrated formulation (100 mg/mL). The mechanistic studies indicated that polymers interacted with the cell and blocked the formation of the entry/fusion complex. Physicochemical and biological properties of PEG(x)-b-PMAPTAC(y) make them promising drug candidates.

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