ABSTRACT
More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(dl-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections.
Subject(s)
Drug Carriers/chemistry , Herpesvirus 2, Human/physiology , Lactic Acid/chemistry , Polyesters/chemistry , Polyglycolic Acid/chemistry , Acyclovir/chemistry , Acyclovir/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Chlorocebus aethiops , Elastic Modulus , Electric Conductivity , Microscopy, Electron, Scanning , Polylactic Acid-Polyglycolic Acid Copolymer , Vero Cells , Virus Internalization/drug effects , ViscosityABSTRACT
A study of the in vitro nanoparticle-templated assembly of a mutant of cowpea chlorotic mottle virus lacking most of the N-terminal domain (residues 4-37), NDelta34, is presented. Mutant empty proteins assemble into empty capsids with a much broader distribution of sizes than the wild-type virus. This increased flexibility in the assembly outcomes is known to be detrimental for the assembly process in the presence of molecular polyanions. However, when rigid polyanionic cores are used, such as nanoparticles, the assembly process is restored and virus-like particles form. Moreover, the breadth of the nanoparticle-templated capsid size distribution becomes comparable with the wild-type virus size distribution.
Subject(s)
Bromovirus/chemistry , Bromovirus/ultrastructure , Capsid/chemistry , Capsid/ultrastructure , Crystallization/methods , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Macromolecular Substances/chemistry , Materials Testing , Molecular Conformation , Mutation , Nanotechnology/methods , Particle Size , Surface PropertiesABSTRACT
A perspective on abiotic material encapsulation inside virus capsids is provided. The emphasis is on the physical principles of virus assembly relevant to packaging, strategies for encapsulation and capsid modification, and on emerging applications.
ABSTRACT
Efficient encapsulation of functionalized spherical nanoparticles by viral protein cages was found to occur even if the nanoparticle is larger than the inner cavity of the native capsid. This result raises the intriguing possibility of reprogramming the self-assembly of viral structural proteins. The iron oxide nanotemplates used in this work are superparamagnetic, with a blocking temperature of about 250 K, making these virus-like particles interesting for applications such as magnetic resonance imaging and biomagnetic materials. Another novel feature of the virus-like particle assembly described in this work is the use of an anionic lipid micelle coat instead of a molecular layer covalently bound to the inorganic nanotemplate. Differences between the two functionalization strategies are discussed.
