No description available.

Transdermal drug delivery systems (TDS) are pharmaceutical devices that are designed to deliver specific drugs to the human body by diffusion through skin. The TDS effectiveness suffers from crystallization in the patch when they are kept in storage for more than two years. It has been reported that there are two types of crystals in the patch: needle and aggregate, and growth of drug crystals in TDS generally occurs only in the middle third of the polymer layer. In our study, fluorescence microscopy, EDS (SEM) and Raman microspectroscopy were used to further characterize the crystals. The results show that the needle crystals most probably contain estradiol and acrylic resin conjugate. The FTIR spectrum of the model sample proved the occurrence of a reaction between estradiol and acrylic resin. Crystal growth in an unstressed matrix of a dissolved crystallizable drug component was simulated using a kinetic Monte Carlo model. Simulation using Potts model with proper boundary condition gives the crystals in the middle of matrix in the higher temperature. Bond fluctuation model is also being implemented to study representative dense TDS polymer matrix. This model can account for the size effect of polymer chain on the crystal growth. The drug release profile from TDS was also studied by simulating the diffusion of drug molecules using Monte Carlo techniques for different initial TDS microstructure. The release rate and profile of TDS depend on the dissolution process of the crystal. At low storage temperature, the grains are evenly distributed throughout the thickness of the TDS patch, thus the release rate and profile is similar to the randomly initiated system. Further work on stress induced crystallization is currently under development. Although the study was specifically done for drug in a polymer medium, the techniques developed in this investigation is in general applicable to any constrained crystallization in a polymer medium.

No description available.

CNT membrane platforms are biomimetic polymeric membranes imbedded with carbon nanotubes which show fast fluid flow, electric conductivity, and the ability to be grafted with chemistry. A novel micro-dialysis probe nicotine concentration sampling technique was proposed and proved in vitro, which could greatly improve the efficiency and accuracy of future animal transdermal studies. To enhance the scope of transdermal drug delivery which was limited to passive diffusion of small, potent lipophilic drugs, a wire mesh lateral electroporation design was also proposed which could periodically disrupt the skin barrier and enhance drug flux. It was shown that AMP binding aptamer at the tip of carbon nanotubes may act as gatekeepers and regulate ionic transport through CNT membrane. Multiple cycle gating of ionic transport upon AMP binding/unbinding which changes the aptamer conformation was displayed. This CNT membrane-aptamer system closely mimics how protein ion channels modulate ion flow by responding to stimuli, which may have significant impact on active membrane transport. Finally an enhanced electroosmosis concept by “ratchet” functionalization at both ends of carbon nanotubes in was discussed. Direct observation of water transport by electroosmosis was made possible through enhanced flow in vertically aligned high flux CNT membranes.

This dissertation presents the development of electrically-powered, lamination-based microactuators for the realization of large arrays of high impulse and short duration micro-jets with potential applications in the field of micro-electro-mechanical systems (MEMS). Microactuators offer unique control opportunities by converting the input electrical or chemical energy stored in a propellant into useful mechanical energy. This small and precise control obtained can potentially be applied towards aerodynamic control and transdermal drug delivery applications. This thesis discusses the development of both chemical and physical microactuators and characterizes their performance with focus towards the feasibility of using them for a specific application. The development of electrically powered microactuators starts by fabricating an array of radially firing microactuators using lamination-based micro fabrication techniques that potentially enable batch fabrication at low cost. The microactuators developed in this thesis consist of three main parts: a micro chamber in which the propellant is stored; two electrode structures through which electrical energy is supplied to the propellant; and a micro nozzle through which the propellant or released gases from the propellant are expanded as a jet. The fabricated actuators are then integrated with MEMS-process-compatible propellants and optimized to produce rapid ignition of the propellant and generate a fluidic jet. This rapid ignition is achieved either by making the propellant itself conductive, thus, passing an electric current directly through the propellant; or by discharging an arc across the propellant by placing it between two closely spaced electrodes. The first concept is demonstrated with chemical microactuators for the application of projectile maneuvering and the second concept is demonstrated with physical microactuators for transdermal drug delivery application. For both the actuators, the propellant integrated microactuators are characterized for performance in terms of impulse delivered, thrust generated and duration of the jet. The experimentally achieved results are validated by comparing with results from theoretical modeling. Finally, the feasibility of using chemical microactuators for maneuvering the path of a 25 mm projectile spinning at 500 Hz is discussed and the feasibility of applying the physical microactuators for increasing skin's permeability to drug analog molecules is studied.

Transdermal drug delivery systems (TDDSs) play important roles in therapy due to distinct advantages over other forms and types of drug application. While common TDDS patches mainly consist of polymeric matrices so far, inorganic carriers show numerous advantages such as high mechanical stability, possible re-use and re-loading of drugs, and a broad chemical compatibility with therapeutically relevant compounds and chemical enhancers. Mesoporous glasses can be prepared in different monolithic shapes, and offer a particularly wide range of possible pore volumes, pore diameters, and specific surface areas. Further, they show high loading capacities and favorable physical, technical, and biological properties. Here, we explored for the first time monolithic SiO2- based carriers as sustained release systems of therapeutic drugs. In an ideally stirred vessel as model system, we systematically analyzed the influence of pore diameter, pore volume, and the dimensions of glass monoliths on the loading and sustained release of different drugs, including anastrozole, xylazine, imiquimod, levetiracetam, and flunixin. Through multilinear regression, we calculated the influence of different parameters on drug loading and diffusion coefficients. The systematic variation of the mesoporous glass properties revealed pore volumes and drug loading concentrations, but not pore diameter or pore surface area as important parameters of drug loading and release kinetics. Other relevant effectors include the occurrence of lateral diffusion within the carrier and drug-specific properties such as adsorption. The structure–property relationships derived from our data will allow further fine-tuning of the systems according to their desired properties as TDDS, thus guiding towards optimal systems for their use in transdermal drug applications

O objetivo do presente trabalho foi de analisar, experimentalmente, a variação do índice de transmissão e o coeficiente de atenuação ultra-sônica no meio diclofenaco gel, bem como, a penetração do fármaco em amostras de gelatina semelhante a pele humana através da fonoforese. A variação destes parâmetros foi investigada em 120 amostras de agar-agar, (modo contínuo, 1 MHz de freqüência, nas intensidades de 1,0 e 1,5 W/\'CM POT.2\'), por 5 minutos. Os corpos de prova forma divididos em grupos referentes as intensidades de ultra-som utilizadas, e cada um destes grupos, foi subdividido em sub-grupos correspondendo aos diferentes meios utilizados para irradiação. A investigação da transmissão ultra-sônica foi medida a partir de um dosímetro de precisão ULTRASONIC POWER METER, modelo UPM-DT 10. O cálculo do coeficiente de atenuação foi realizado a partir dos dados de leitura da transmissão ultra-sônica. A penetração ou não da droga foi estudada por análise macroscópica e microscópica. Segundo os resultados obtidos não houve variação significativa nos índices de transmissão e nos coeficientes de atenuação do diclofenaco gel em comparação ao gel neutro. A penetração do medicamento foi de 3 mm para as amostras irradiadas com a intensidade de 1,0 W/\'CM POT.2\' e de 5 mm para as amostras irradiadas com 1,5 W/\'CM POT.2\', não houve evidência de penetração do fármaco no grupo controle. Os resultados obtidos neste estudo sugerem que a fonoforese do diclofenaco gel é efetiva nas intensidades 1,0 e 1,5 W/\'CM POT.2\'. / The objective of the present work was of analyzing, experimentally, the variation of the transmission index and the coefficient of ultrasonic reduction in the half diclofenaco gel, as well as, the penetration of the drug in samples of similar jelly the human skin through the phonophoresis. The variation of these parameters was investigated in 120 agar-agar samples, (continuous way, 1 MHz of frequency, in the intensities of 1,0 and 1,5 W/\'CM POT.2\'), for 5 minutes. The proof bodies form divided in referring groups the ultrasound intensities used, and each one of these groups, it was subdivided in sub-groups corresponding to the different means used for irradiation. The investigation of the ultrasonic transmission was measured starting from a ULTRASONIC POWER METER, model UPM-DT 10. The calculate it of the reduction coefficient was accomplished starting from the data of reading of the ultrasonic transmission. The penetration or not of the drug it was studied for it analyzes macroscopic and microscopic. According to the obtained results there was not significant variation in the transmission indexes and in the coefficients of reduction of the diclofenaco gel in comparison with the neutral gel. The penetration of the medicine went of 3 mm to the samples irradiated with the intensity of 1,0 W/\'CM POT.2\' and of 5 mm for the samples irradiated with 1,5 W/\'CM POT.2\', there was not evidences of penetration of the drug in the group control. The results obtained in this study suggest that the phonophoresis of the diclofenaco gel is effective in the intensities 1,0 and 1,5 W/\'CM POT.2\'.

A proposta deste estudo foi comparar a eficácia de tratamento da aplicação tópica de hidrocortisona, do ultra-som terapêutico e da fonoforese no processo de reparo do tendão de Aquiles (tendo calcaneus) de ratos, após tenotomia. O grupo controle foi definido como tenotomizados com simulação da aplicação sônica e tendões não tenotomizados. Os dois grupos tratados com ultra-som terapêutico foram no modo pulsado. A irradiação do ultra-som terapêutico foi realizada na freqüência de 1 MHz e uma intensidade de 0.5 Watts por centímetro ao quadrado (SATA), por cinco minutos cada sessão. No 13° dia de pós-operatório, os tendões foram removidos e analisados por meio da microscopia de luz polarizada, com o propósito de investigar e medir a organização das fibras de colágeno, por meio da birrefringência. Os resultados demonstraram que o grupo tratado com a aplicação tópica de hidrocortisona apresentou valores estatísticos similares ao grupo que recebeu simulação sônica, indicando que não houve penetração da hidrocortisona e que as moléculas de colágeno responderam a estimulação ultra-sônica. Tal fato acontece provavelmente originado pelo efeito piezoelétrico que o ultra-som causa no tecido. O tratamento com fonoforese demonstrou ser o método mais eficiente, devido a maior birrefringência, revelando melhor organização e agregação das fibras de colágeno. Esses achados permitem concluir que o ultra-som terapêutico estimula a aceleração do processo de reparo tecidual e induz a penetração transcutânea da hidrocortisona a 10% numa concentração terapêutica / The purpose of this study was to compare the treatment efficacy of topic hydrocortisone appliance, therapeutic ultrasound and phonophoresis on the rats’ Achilles tendon (tendo calcaneus) repair process after tenotomy. The control group was designed in tenotomized with sham sonic application and non-tenotomized tendons. The two treated groups with therapeutic ultrasound was made in a pulsed mode. The irradiation of therapeutic ultrasound was performed at a frequency of 1 MHz and an intensity of 0.5 Watts for square centimeter (SATA), for five minutes each session. On the 13 th postoperative day, the tendons were removed and analyzed using the polarized light microscopy, with the purpose to detect and measure the organization of collagen fibers through birefringence. The results showed that the treated group with the hydrocortisone topic appliance showed similar statistician values of group that received sham sonic treatment, indicating that not have delivery transdermal and that the molecule of collagen respond to the ultrasonic stimulation. This fact occurs probably by piezoelectric effect originated by ultrasound on the tissue. The treatment with phonophoresis demonstrated being the method more efficient, due the high birefringence, revealing the best organization and aggregation of collagen fibers. These findings allow conclude that the therapeutic ultrasound stimulate the acceleration of tissue repair process and induce the transdermal delivery of hydrocortisone 10% in a therapeutic concentration

The world-wide transdermal drug delivery market is quite large, but only a small number of agents have FDA approval. The primary reason for such limited development is the difficulty in permeating the stratum corneum layer of human skin. In our study, we developed a novel percutaneous delivery enhancing approach. Magainin peptide was previously shown to disrupt vesicles from stratum corneum lipid components and this ability of magainin allows us to propose that magainin can increase skin permeability. Therefore, we tested the hypothesis that magainin, a pore-forming peptide, can increase skin permeability by disrupting stratum corneum lipid structure and that magainin¡¯s enhancement requires co-administration of a surfactant chemical enhancer to increase magainin penetration into the skin. In support of these hypotheses, synergistic enhancement of transdermal permeation can be observed with magainin peptide in combination of N-lauroyl sarcosine (NLS) in 50% ethanol-PBS solution. The exposure to NLS in 50% ethanol solution increased in vitro skin permeability to fluorescein 15 fold and the addition of magainin synergistically increased skin permeability 47 fold. In contrast, skin permeability was unaffected by exposure to magainin without co-enhancement by NLS-ethanol. To elucidate the mechanism of this synergistic effect, several characterization methods such as differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction were applied. These analyses showed that NLS-ethanol disrupted stratum corneum lipid structure and that the combination of magainin and NLS-ethanol disrupted stratum corneum lipids even further. Furthermore, confocal microscopy showed that magainin in the presence of NLS-ethanol penetrated deeply and extensively into stratum corneum, whereas magainin alone penetrated poorly into the skin. Together, these data suggest that NLS-ethanol increased magainin penetration into stratum corneum, which further increased stratum corneum lipid disruption and skin permeability. Finally, skin permeability was enhanced by changing the charge of magainin peptide via pH change. We modulated pH from 5 to 11 to change the magainin charge from positive to neutral, which decreased skin permeability to a negatively charged fluorescein and increased skin permeability to a positively charged granisetron. This suggests that an attractive interaction between the drug and magainin peptide improves transdermal flux.

O objetivo do presente trabalho foi de analisar, experimentalmente, a variação do índice de transmissão e o coeficiente de atenuação ultra-sônica no meio diclofenaco gel, bem como, a penetração do fármaco em amostras de gelatina semelhante a pele humana através da fonoforese. A variação destes parâmetros foi investigada em 120 amostras de agar-agar, (modo contínuo, 1 MHz de freqüência, nas intensidades de 1,0 e 1,5 W/\'CM POT.2\'), por 5 minutos. Os corpos de prova forma divididos em grupos referentes as intensidades de ultra-som utilizadas, e cada um destes grupos, foi subdividido em sub-grupos correspondendo aos diferentes meios utilizados para irradiação. A investigação da transmissão ultra-sônica foi medida a partir de um dosímetro de precisão ULTRASONIC POWER METER, modelo UPM-DT 10. O cálculo do coeficiente de atenuação foi realizado a partir dos dados de leitura da transmissão ultra-sônica. A penetração ou não da droga foi estudada por análise macroscópica e microscópica. Segundo os resultados obtidos não houve variação significativa nos índices de transmissão e nos coeficientes de atenuação do diclofenaco gel em comparação ao gel neutro. A penetração do medicamento foi de 3 mm para as amostras irradiadas com a intensidade de 1,0 W/\'CM POT.2\' e de 5 mm para as amostras irradiadas com 1,5 W/\'CM POT.2\', não houve evidência de penetração do fármaco no grupo controle. Os resultados obtidos neste estudo sugerem que a fonoforese do diclofenaco gel é efetiva nas intensidades 1,0 e 1,5 W/\'CM POT.2\'. / The objective of the present work was of analyzing, experimentally, the variation of the transmission index and the coefficient of ultrasonic reduction in the half diclofenaco gel, as well as, the penetration of the drug in samples of similar jelly the human skin through the phonophoresis. The variation of these parameters was investigated in 120 agar-agar samples, (continuous way, 1 MHz of frequency, in the intensities of 1,0 and 1,5 W/\'CM POT.2\'), for 5 minutes. The proof bodies form divided in referring groups the ultrasound intensities used, and each one of these groups, it was subdivided in sub-groups corresponding to the different means used for irradiation. The investigation of the ultrasonic transmission was measured starting from a ULTRASONIC POWER METER, model UPM-DT 10. The calculate it of the reduction coefficient was accomplished starting from the data of reading of the ultrasonic transmission. The penetration or not of the drug it was studied for it analyzes macroscopic and microscopic. According to the obtained results there was not significant variation in the transmission indexes and in the coefficients of reduction of the diclofenaco gel in comparison with the neutral gel. The penetration of the medicine went of 3 mm to the samples irradiated with the intensity of 1,0 W/\'CM POT.2\' and of 5 mm for the samples irradiated with 1,5 W/\'CM POT.2\', there was not evidences of penetration of the drug in the group control. The results obtained in this study suggest that the phonophoresis of the diclofenaco gel is effective in the intensities 1,0 and 1,5 W/\'CM POT.2\'.