RESUMEN
The development of potent antibiotic alternatives with rapid bactericidal properties is of great importance in addressing the current antibiotic crisis. One representative example is the topical delivery of predatory bacteria to treat ocular bacterial infections. However, there is a lack of suitable methods for the delivery of predatory bacteria into ocular tissue. This work introduces cryomicroneedles (cryoMN) for the ocular delivery of predatory Bdellovibrio bacteriovorus (B. bacteriovorus) bacteria. The cryoMN patches are prepared by freezing B. bacteriovorus containing a cryoprotectant medium in a microneedle template. The viability of B. bacteriovorus in cryoMNs remains above 80% as found in long-term storage studies, and they successfully impede the growth of gram-negative bacteria in vitro or in a rodent eye infection model. The infection is significantly relieved by nearly six times through 2.5 days of treatment without substantial effects on the cornea thickness and morphology. This approach represents the safe and efficient delivery of new class of antimicrobial armamentarium to otherwise impermeable ocular surface and opens up new avenues for the treatment of ocular surface disorders.
Asunto(s)
Bdellovibrio bacteriovorus/fisiología , Infecciones del Ojo/microbiología , Inyecciones Intraoculares/métodos , Administración Tópica , Animales , Bdellovibrio bacteriovorus/crecimiento & desarrollo , Córnea/anatomía & histología , Córnea/fisiología , Modelos Animales de Enfermedad , Infecciones del Ojo/diagnóstico por imagen , Infecciones del Ojo/terapia , Bacterias Gramnegativas/fisiología , Inyecciones Intraoculares/instrumentación , Masculino , Ratones , Ratones Endogámicos C57BL , Agujas , Tomografía de Coherencia ÓpticaRESUMEN
Topical drug delivery has inherent advantages over other administration routes. However, the existence of stratum corneum limits the diffusion to small and lipophilic drugs. Fortunately, the advancement of nanotechnology brings along opportunities to address this challenge. Taking the unique features in size and surface chemistry, nanocarriers such as liposomes, polymeric nanoparticles, gold nanoparticles, and framework nucleic acids have been used to bring drugs across the skin barrier to epidermis and dermis layers. This article reviews the development of these formulations and focuses on their applications in the treatment of skin disorders such as acne, skin inflammation, skin infection, and wound healing. Existing hurdles and further developments are also discussed.
Asunto(s)
Fármacos Dermatológicos/administración & dosificación , Portadores de Fármacos/química , Nanopartículas/química , Enfermedades de la Piel/tratamiento farmacológico , Administración Cutánea , Animales , Fármacos Dermatológicos/farmacocinética , Modelos Animales de Enfermedad , Composición de Medicamentos , Liberación de Fármacos , Oro/química , Humanos , Ácidos Nucleicos/química , Polímeros/química , Dióxido de Silicio/química , Piel/metabolismoRESUMEN
Small interfering RNA (siRNA) is a promising tool for the treatment of skin disorders including skin squamous cell carcinoma (SCC). This article develops a topical formulation for the transdermal delivery of siRNA. The formulation is built on mesoporous silica nanoparticles (MSNPs) with a loading capacity of 1.4 µg of oligonucleotide per mg of MSNPs. Cell experiments are employed to study the functionality of the formulation including the cellular uptake, the qualitative and quantitative detection of specific gene biomarkers. The clinical potential of this system is examined by topically delivering siRNA targeting TGFßR-1 (TGFßR-1) to the SCC in a mouse xenograft model. In comparison to the controls, MSNPs containing TGFßR-1 siRNA show a 2-fold suppression of TGFßR-1.