RESUMEN
In this study, we present transcutaneous influenza vaccination using a novel tip-separable microneedle system called insertion-responsive microneedles (IRMNs). IRMNs are composed of dissolvable hyaluronic acid (HA) tips and biocompatible polycaprolactone (PCL) bases, the tip of which is instantly separated from the base during microneedle insertion and retraction. Vaccine antigens derived from canine influenza virus (A/canine/VC378/2012; H3N2) were successfully coated on HA tips by rapidly freezing the tips prior to coating. An ex vivo porcine skin insertion test showed that IRMNs were capable of penetrating the skin without tip breakage and releasing the coated materials within the skin. The thermal stability of the vaccine as determined by hemagglutination assay revealed that the coated vaccine partially maintained its activity when stored at 50⯰C for 3â¯weeks, whereas the liquid form completely lost the activity. Immunization in guinea pigs showed that hemagglutination inhibition (HI) antibodies induced by IRMNs were two times higher than those induced by intramuscular (IM) injections. When challenged with influenza A/canine/Korea/01/2007 (H3N2) wild-type virus 2â¯weeks after the second vaccination, viral shedding was completely eliminated at 8â¯days post infection in both IRMNs and IM injection groups. Our results suggest that IRMNs have great potential for rapid and convenient vaccination, which will be particularly attractive for animal vaccinations.
Asunto(s)
Enfermedades de los Perros/prevención & control , Vacunas contra la Influenza/administración & dosificación , Infecciones por Orthomyxoviridae/prevención & control , Vacunación/instrumentación , Animales , Línea Celular , Enfermedades de los Perros/inmunología , Perros , Sistemas de Liberación de Medicamentos/economía , Sistemas de Liberación de Medicamentos/instrumentación , Diseño de Equipo , Femenino , Cobayas , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/uso terapéutico , Inyecciones Intradérmicas , Microinyecciones/economía , Microinyecciones/instrumentación , Agujas , Infecciones por Orthomyxoviridae/inmunología , Porcinos , Factores de Tiempo , Vacunación/economíaRESUMEN
OBJECTIVE: Currently available measles vaccines are administered by subcutaneous injections and require reconstitution with a diluent and a cold chain, which is resource intensive and challenging to maintain. To overcome these challenges and potentially increase vaccination coverage, microneedle patches are being developed to deliver the measles vaccine. This study compares the cost-effectiveness of using microneedle patches with traditional vaccine delivery by syringe-and-needle (subcutaneous vaccination) in children's measles vaccination programs. METHODS: We built a simple spreadsheet model to compute the vaccination costs for using microneedle patch and syringe-and-needle technologies. We assumed that microneedle vaccines will be, compared with current vaccines, more heat stable and require less expensive cool chains when used in the field. We used historical data on the incidence of measles among communities with low measles vaccination rates. RESULTS: The cost of microneedle vaccination was estimated at US$0.95 (range US$0.71-US$1.18) for the first dose, compared with US$1.65 (range US$1.24-US$2.06) for the first dose delivered by subcutaneous vaccination. At 95 % vaccination coverage, microneedle patch vaccination was estimated to cost US$1.66 per measles case averted (range US$1.24-US$2.07) compared with an estimated cost of US$2.64 per case averted (range US$1.98-US$3.30) using subcutaneous vaccination. CONCLUSIONS: Use of microneedle patches may reduce costs; however, the cost-effectiveness of patches would depend on the vaccine recipients' acceptability and vaccine effectiveness of the patches relative to the existing conventional vaccine-delivery method. This study emphasizes the need to continue research and development of this vaccine-delivery method that could boost measles elimination efforts through improved access to vaccines and increased vaccination coverage.
Asunto(s)
Vacuna Antisarampión/administración & dosificación , Vacuna Antisarampión/economía , Microinyecciones/economía , Agujas/economía , Parche Transdérmico/economía , Preescolar , Análisis Costo-Beneficio , Humanos , Inyecciones SubcutáneasRESUMEN
Millions of people die of infectious diseases each year, mostly in developing countries, which could largely be prevented by the use of vaccines. While immunization rates have risen since the introduction of the Expanded Program on Immunization (EPI), there remain major challenges to more effective vaccination in developing countries. As a possible solution, microneedle patches containing an array of micron-sized needles on an adhesive backing have been developed to be used for vaccine delivery to the skin. These microneedle patches can be easily and painlessly applied by pressing against the skin and, in some designs, do not leave behind sharps waste. The patches are single-dose, do not require reconstitution, are easy to administer, have reduced size to simplify storage, transportation and waste disposal, and offer the possibility of improved vaccine immunogenicity, dose sparing and thermostability. This review summarizes vaccination challenges in developing countries and discusses advantages that microneedle patches offer for vaccination to address these challenges. We conclude that microneedle patches offer a powerful new technology that can enable more effective vaccination in developing countries.
Asunto(s)
Control de Enfermedades Transmisibles/métodos , Países en Desarrollo , Microinyecciones/métodos , Agujas , Parche Transdérmico , Vacunación/métodos , Animales , Control de Enfermedades Transmisibles/economía , Control de Enfermedades Transmisibles/normas , Enfermedades Transmisibles/economía , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/terapia , Países en Desarrollo/economía , Humanos , Inyecciones Intradérmicas , Microinyecciones/economía , Microinyecciones/normas , Agujas/economía , Agujas/normas , Parche Transdérmico/economía , Parche Transdérmico/normas , Vacunación/economía , Vacunación/normasRESUMEN
BACKGROUND: In in vitro electrophysiological studies, a quick application of picoliters of drug within milliseconds is required to avoid the desensitization of membrane receptors. However, conventional gravity-fed drug delivery devices sometime fail to achieve this. Moreover, the high financial cost of the advanced drug delivery system often limits the application of commercial instruments in academic research. NEW METHOD: Taking advantage of the availability of data acquisition system and software in almost every electrophysiology laboratory, a simple puffing device was designed and assembled using low-cost commercially off-the-shelf components to inject picoliter amounts of drugs. RESULTS: An optimal drug delivery with precise timing and volume was achieved using the custom made puffing device. The glutamate-evoked currents of cortical neurons recorded with patch-clamp technique were maintained for a prolonged period of time. Similarly, puffed inhibitory transmitters including GABA and glycine also produced satisfactory currents. COMPARISON WITH EXISTING METHOD(S): Our custom-made puffing system holds the advantage over conventional gravity-fed systems in operating within milliseconds of time. The channel number of the new device can easily be increased by simply adding more identical modules in parallel, and thus offering more flexibility than commercial puffing devices. CONCLUSIONS: This custom-made puffing device can be characterized as reliable, modular and inexpensive system for modern drug delivery research and application.
Asunto(s)
Sistemas de Liberación de Medicamentos/instrumentación , Sistemas de Liberación de Medicamentos/métodos , Técnicas de Placa-Clamp/instrumentación , Animales , Células Cultivadas , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiología , Sistemas de Liberación de Medicamentos/economía , Diseño de Equipo , Ácido Glutámico/administración & dosificación , Glicina/administración & dosificación , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Microinyecciones/economía , Microinyecciones/instrumentación , Microinyecciones/métodos , Morfolinas , Neuronas/efectos de los fármacos , Neuronas/fisiología , Neurotransmisores/administración & dosificación , Técnicas de Placa-Clamp/economía , Técnicas de Placa-Clamp/métodos , Presión , Ratas Sprague-Dawley , Programas Informáticos , Ácido gamma-Aminobutírico/administración & dosificaciónRESUMEN
With interest in microneedles as a novel drug transdermal delivery system increasing rapidly since the late 1990s (Margetts and Sawyer Contin Educ Anaesthesia Crit Care Pain. 7(5):171-76, 2007), a diverse range of microneedle systems have been fabricated with varying designs and dimensions. However, there are still very few commercially available microneedle products. One major issue regarding microneedle manufacture on an industrial scale is the lack of specific quality standards for this novel dosage form in the context of Good Manufacturing Practice (GMP). A range of mechanical characterisation tests and microneedle insertion analysis techniques are used by researchers working on microneedle systems to assess the safety and performance profiles of their various designs. The lack of standardised tests and equipment used to demonstrate microneedle mechanical properties and insertion capability makes it difficult to directly compare the in use performance of candidate systems. This review highlights the mechanical tests and insertion analytical techniques used by various groups to characterise microneedles. This in turn exposes the urgent need for consistency across the range of microneedle systems in order to promote innovation and the successful commercialisation of microneedle products.
Asunto(s)
Microinyecciones/instrumentación , Agujas/normas , Transferencia de Tecnología , Tecnología Farmacéutica/normas , Humanos , Inyecciones Intradérmicas , Microinyecciones/economía , Agujas/economía , Tecnología Farmacéutica/economía , Tecnología Farmacéutica/métodosRESUMEN
Neurons are functionally segregated into discrete populations that perform specific computations. These computations, mediated by neuron-neuron electrochemical signaling, form the neural basis of behavior. Thus fundamental to a brain-based understanding of behavior is the precise determination of the contribution made by specific neurotransmitters to behaviorally relevant neural activity. To facilitate this understanding, we have developed a cannulated microelectrode array for use in behaving rats that enables simultaneous neural ensemble recordings and local infusion of drugs in the same brain nucleus. The system is inexpensive, easy to use, and produces robust and quantitatively reproducible drug effects on recorded neurons.
Asunto(s)
Conducta Animal/fisiología , Encéfalo/fisiología , Cateterismo/instrumentación , Electrodos Implantados , Bombas de Infusión , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Cateterismo/economía , Cateterismo/métodos , Electrodos Implantados/economía , Bombas de Infusión/economía , Lidocaína/administración & dosificación , Masculino , Microelectrodos/economía , Microinyecciones/economía , Microinyecciones/instrumentación , Microinyecciones/métodos , Ratas , Ratas Long-EvansRESUMEN
Intracytoplasmic sperm injection (ICSI) with in vitro fertilization represents one of the most significant advances in fertility technology. In this relatively new procedure, a single viable sperm is microinjected into an oocyte that has been extracted transvaginally. After fertilization occurs, the embryo is transferred into the uterus. This procedure now affords men who were previously thought to be irreversibly infertile the chance to initiate their own biologic pregnancy. However, because of the procedure's significant costs and its potential risk to the mother, careful selection of couples following a thorough male factor evaluation is mandatory.
Asunto(s)
Fertilización In Vitro/métodos , Infertilidad Masculina/terapia , Oocitos , Espermatozoides , Anomalías Congénitas/etiología , Costos y Análisis de Costo , Femenino , Fertilización In Vitro/economía , Humanos , Masculino , Edad Materna , Ciencia del Laboratorio Clínico , Microinyecciones/economía , Microinyecciones/métodos , Oligospermia/patología , Oocitos/ultraestructura , Selección de Paciente , Embarazo , Factores de Riesgo , Capacitación Espermática , Motilidad Espermática , Interacciones Espermatozoide-Óvulo , Transferencia Intrafalopiana del CigotoRESUMEN
Central to the process of making transgenic mice is the physical introduction of cloned DNA fragments into fertilized one-cell mouse eggs. First described 10 years ago by a number of investigators, microinjection remains the most popular and successful of the methods currently available for generating transgenic animals. Microinjection continues to be the method of choice, because the advantages of speed and reliability far outweigh the demands placed on the investigator for precise technical skill and expensive equipment.
Asunto(s)
ADN/química , ADN/genética , Microinyecciones/métodos , Cigoto/citología , Cigoto/metabolismo , Animales , Clonación Molecular , ADN/metabolismo , Femenino , Ratones , Microinyecciones/economía , Microinyecciones/instrumentaciónRESUMEN
In recent years, a number of automatic microinjection systems have appeared on the market. These systems replace the simple manual syringe system for forcing the DNA solution out of the microinjection pipet and into the pronucleus of a fertilized one-cell egg. The advantages of such automatic systems are twofold: (1) Because injection is triggered by a foot-operated peddle, the hands are left free to operate the joy-stick controls of the micromanipulators. Since the hands are not constantly moving from one piece of apparatus to another, the process of microinjection is speeded up considerably. (2) Through the application of a low, constant (balance) pressure, DNA solution is flowing out of the holding pipet throughout the injection session. This prevents back-flow of M2 medium into the injection pipet, which would otherwise considerably dilute the DNA solution, and it also prevents blockage of the pipet. Using an automatic injection system, it is found that pipets need not be changed as often as required when using a manually operated system. This chapter describes the operation of an economical injection system supplied by the Narishige company (Tokyo).
Asunto(s)
ADN/química , ADN/genética , Microinyecciones/métodos , Cigoto/citología , Cigoto/metabolismo , Animales , Automatización , Clonación Molecular , ADN/metabolismo , Ratones , Microinyecciones/economía , Microinyecciones/instrumentaciónRESUMEN
A picoliter pressure ejection system, which is constructed from readily available and inexpensive components, is described. Pressure pulse duration and interpulse interval are controllable by either internal circuitry or by external signals from stimulators or computers. The control features and linearity of ejection volumes are similar to those of more expensive commercial units.