- Full text PDF available (2)
Hydrogel nanoparticles (HNP) are an emerging tool of biomedicine with unique materials characteristics, scope, and utility. These hydrated, soft colloidal carriers can penetrate through voids with dimensions narrower than the size of the particle, provide stabilization for fragile biological cargo and allow diffusion and exchange of solutes with external… (More)
Due to its versatility and ease of use the layer-by-layer (LbL) assembly technique has been under intensive investigation for drug and gene delivery applications. Especially the development of responsive LbL materials has advanced significantly in recent years. Responsiveness plays an important role in many delivery applications, either for loading of… (More)
Chemi-enzymatic synthesis of ribavirin acrylate and subsequent RAFT co-polymerization with acrylic acid afforded a formulation of a broad spectrum antiviral drug which avoids accumulation in erythrocytes, the origin of the main side effect of ribavirin. In cultured macrophages the macromolecular prodrugs exhibited decreased toxicity while maintaining the… (More)
Ribavirin (RBV), a broad-spectrum antiviral agent, is a standard medication against hepatitis C virus (HCV). However, despite the decades of clinical success, the mechanism of action of this drug against HCV remains a subject of debate. Furthermore, the appeal of this therapeutic agent is considerably lessened by unfavorable pharmacokinetics. This… (More)
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) represent tremendous healthcare burdens with a large proportion of patients hosting the two viruses at the same time. An altered hepatic function and immunity as well as cross-interference of drugs make treatment of co-infection increasingly challenging. Herein we report the first design of… (More)
Macromolecular prodrugs are developed as multiarmed agents against diverse viral pathogens. Lead candidates inhibit infectivity and replication of HIV, Ebola, influenza, measles, RSV, etc-thus being broad-spectrum antiviral agents.
The release of azidothymidine from macromolecular prodrugs was designed to respond to the intracellular disulfide reshuffling. This drug has no thiol groups, and a response to this trigger was engineered using a self-immolative linker. The resulting formulations were fast-acting, efficacious, and highly potent with regards to suppressing the infectivity of… (More)
We report the first successful implementation of transfection agents to facilitate the delivery of non-nucleic acid based anti-inflammatory and anti-viral drugs. In doing so, we illustrate a new paradigm in the intracellular delivery of polyanionic drugs and also extend the scope and utility of successful tools of gene transfer into a new area of biomedical… (More)
Polymers in tune. Automated parallel polymer synthesis is developed to obtain libraries of macromolecular prodrugs of ribavirin, a broad-spectrum antiviral agent. As many as 10 identified lead polymer conjugates exhibit therapeutic efficacy matching that of the pristine drug and at the same time suppressed the origin of the main side effect of ribavirin.
Efficacious, potent, and at the same time nontoxic macromolecular prodrugs of ribavirin are designed taking advantage over prodrug activation by the intracellular milieu. Activity of these prodrugs is illustrated in the cells hosting hepatitis C virus replication and also in the cells implicated in the inflammatory response to the viral infection.