RESUMO
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.
Assuntos
Portadores de Fármacos/química , Herpesvirus Humano 2/fisiologia , Ácido Láctico/química , Poliésteres/química , Ácido Poliglicólico/química , Aciclovir/química , Aciclovir/farmacologia , Animais , Antivirais/química , Antivirais/farmacologia , Chlorocebus aethiops , Módulo de Elasticidade , Condutividade Elétrica , Microscopia Eletrônica de Varredura , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Células Vero , Internalização do Vírus/efeitos dos fármacos , ViscosidadeRESUMO
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.
Assuntos
Bromovirus/química , Bromovirus/ultraestrutura , Capsídeo/química , Capsídeo/ultraestrutura , Cristalização/métodos , Nanopartículas/química , Nanopartículas/ultraestrutura , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Mutação , Nanotecnologia/métodos , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
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.