Ion-exchange fibers and drugs: a novel device for the screening of iontophoretic systems.

The objective of this study was to theoretically model and experimentally measure the extent of drug release from ion-exchange fibers. The release was measured as a function of current density and NaCl concentration using a novel iontophoretic cell. The fibers tested contained weak carboxylate (-COOH) ion-exchange groups. The cationic model drugs tacrine and metoprolol were chosen on the basis of previous research, where tacrine had the lowest release rate and metoprolol the highest release rate. An in-house designed three compartment test cell was developed to test the suitability of drugs for iontophoretic drug delivery. In this cell, the anode and the drug containing ion-exchange fiber compartments were separated with a Nafion ion-selective membrane, while the fiber and the return electrode compartments were separated with a porous membrane. Tacrine proved to be a good drug candidate for this system as the release of the tacrine from the device was controllable with salt concentration and current density. Metoprolol release from the device was, however, not controllable.     

Gelatin-stabilised microemulsion-based organogels: rheology and application in iontophoretic transdermal drug delivery

Gelatin-containing microemulsion-based organogels (MBGs) have been formulated using pharmaceutically acceptable surfactants and oils such as Tween 85 and isopropyl myristate. MBG formulations were subject to rheological study and their utility in transdermal drug delivery examined. Unlike most organogels, MBGs are electrically conducting and have been successfully employed in this study for the iontophoretic delivery of a model drug through excised pig skin. Iontophoresis using MBGs gave substantially higher release rates for sodium salicylate compared to passive diffusion, and fluxes were proportional to the drug loading and the current density. MBGs provide a convenient means of immobilising the drug and are rheologically similar to their hydrogel counterparts at comparable gelatin concentrations. MBGs also appear to offer improved microbial resistance in comparison to aqueous solution or hydrogels.     

Ion-exchange fibers and drugs: a transient study.

The objective of this study was to theoretically model and experimentally measure the kinetics and extent of drug release from different ion-exchange materials using an in-house-designed flow-cell. Ion-exchange fibers (staple fibers and fiber cloth) were compared with commercially available ion-exchange materials (resins and gels). The functional ion-exchange groups in all the materials were weak -COOH or strong -SO3H groups. The rate and extent of drug release from the fibers (staple fiber>fiber cloth) was much higher than that from the resin or the gel. An increase in the hydrophilicity of the model drugs resulted in markedly higher rates of drug release from the fibers (nadolol>metoprolol>propranolol>tacrine). Theoretical modelling of the kinetics of ion exchange provided satisfactory explanations for the experimental observations: firstly, a change in the equilibrium constant of the ion-exchange reaction depending on the drug and the ion-exchange material and, secondly, a decrease in the Peclet number (Pe) with decreasing flow-rate of the drug-releasing salt solution.     

Ion-exchange fibers and drugs: an equilibrium study.

The purpose of this study was to investigate the mechanisms of drug binding into and drug release from cation-exchange fibers in vitro under equilibrium conditions. Ion-exchange groups of the fibers were weakly drug binding carboxylic acid groups (-COOH), strongly drug binding sulphonic acid groups (-SO(3)H), or combinations thereof. Parameters determining the drug absorption and drug release properties of the fibers were: (i) the lipophilicity of the drug (tacrine and propranolol are lipophilic compounds, nadolol is a relatively hydrophilic molecule), (ii) the ion-exchange capacity of the fibers, which was increased by activating the cation-exchange groups with NaOH, (iii) the ionic strength of the extracting salt (NaCl), which was studied in a range of 1.5 mM to 1.5 M, and finally (iv) the effect of divalent calcium ions (CaCl(2)) on the release of the model drugs, which was tested and compared to monovalent sodium ions (NaCl), and combinations thereof. It was found that the lipophilic drugs, tacrine and propranolol, were retained in the fibers more strongly and for longer than the more hydrophilic nadolol. The more hydrophilic nadolol was released to a greater extent from the fibers containing strong ion-exchange groups (-SO(3)H), whereas the lipophilic drugs were attached more strongly to strong ion-exchange groups and released more easily from the weak (-COOH) ion-exchange groups. The salt concentration and the choice of the salt also had an effect: at lower NaCl concentrations more drug was released as a result of the influence of both electrostatic and volume effects (equimolar drug:salt ratio). Incorporation of CaCl(2) in the bathing solution increased drug release considerably as compared to NaCl alone. The equilibrium distribution of the drug species between the fiber and external solution phases was also simulated and it was found that the theoretical modelling proposed describes adequately the basic trends of the behavior of these systems.     

Iontophoretic delivery of drugs: Fundamentals,developments and biomedical applications

Iontophoretic drug delivery implies the delivery of ionic (charged) drugs into the body by the use of electric current. The technique is not new and has been used clinically in delivering medication to surface tissues for several decades. However, its potential is recently being rediscovered for transdermal systemic delivery of ionic drugs including peptide/protein drugs which are normally difficult to administer except by parenteral route. The technique has been observed to enhance the transdermal permeation of ionic drugs severalfold, and this can expand the horizon of transdermal controlled drug delivery for systemic medication. However, miniaturization of iontophoretic devices and electrodes and prevention of any possibility of skin burns are required to make this technique useful for biomedical applications. While the literature on iontophoretic systemic drug delivery is relatively recent and not extensive, the published results on clinical usage and other related aspects can be quite informative and could stimulate and assist the readers to explore other biomedical applications. This article is intended to review old as well as very recent literature on the technique, methodology, clinical findings, influencing factors, relevant electronics and other related aspects of iontophoretic drug delivery, and to provide the readers a comprehensive overview of the state-of-art of this potential new area of biomedical research.     

In vitro transdermal iontophoretic transport of timolol maleate: effect of age and species.

Transdermal iontophoresis would be a promising method for the systemic delivery of water soluble and ionic drugs of relatively high molecular size, including peptides. In the present study, the effect of biological parameters such as age of the animal and species variation (rat, rabbit, mouse, guinea pig and human) on the transdermal iontophoretic transport was studied using timolol maleate (TM) as a model drug. The iontophoretic transport of TM across the skins obtained from the rats of different age groups was found to be similar. The results of the present study suggest that the age of the animal (Wistar rats: 1-8 months) did not appear to influence the transdermal iontophoretic transport of TM significantly. The amount of TM transported during iontophoresis (2 h) was significantly different among the different skin species. But the total amount of TM transported up to 24 h (2 h iontophoresis+22 h post-iontophoretic passive diffusion) was not significantly different among the different species studied. The present study provides further evidence that iontophoresis technique reduces the interspecies differences in the transdermal permeation of drugs, which is normally observed in passive diffusion of drugs. However, it must be noted that excised skins have been used in the present study to investigate the role of age and species variation on the iontophoretic transport of TM. The influence of these parameters under in vivo conditions might be different considering the physiological differences in different species and in the animals of different age groups.     

Optimization of iontophoretic transdermal delivery of a peptide and a non-peptide drug

In vitro iontophoretic transdermal delivery (ITD) of a tripeptide, enalaprilat (EP) and a non-peptide, cromolyn sodium (CS), across frozen hairless guinea pig (HGP) skin were investigated. Parameters for optimization of ITD included the influence of ionic strength (μ), buffer type and size, drug loading in the donor and the effect of pH. Drug permeation into the receptor compartment was monitored using HPLC assay methods developed for the study. An optimum μ of 6.66 mM in acetate buffer was found necessary for efficient ITD of CS. An exponential decrease in the flux of CS was observed with an increasing μ. Buffer ions larger than acetate ions inhibited the transport of CS ions. With an increase in the donor concentration of CS, a hyperbolic relationship for the increase in flux was observed. For EP, permeation was not detectable when μ was increased to greater than 31 mM in phosphate-buffered solution. With an increase in pH above the pK_a1 (3.55) for EP, a linear decrease in flux was observed. Higher drug loading of EP in the donor compartment provided better permeation. Effect of freezing of HGP skin on the iontophoretic delivery of EP and CS was also evaluated. Flux values for either of the drugs studied were similar when frozen or fresh skins were used. Reversibility studies indicated that no gross current induced permeation changes occurred with the HGP skin. Passive permeation of either of the drugs investigated was negligible.     

Transdermal iontophoresis of the dopamine agonist 5-OH-DPAT in human skin in vitro.

The feasibility of transdermal iontophoretic delivery of a potent dopamine agonist 5-OH-DPAT was studied in vitro in side by side diffusion cells across human stratum corneum (HSC) and dermatomed human skin (DHS) according to the following protocol: 6 h of passive diffusion, 9 h of iontophoresis and 5 h of passive diffusion. The influences of the following parameters on the flux were studied: donor solution pH, NaCl concentration, drug donor concentration, current density and skin type. A current density of 0.5 mA cm(-2) was used, except for one series of experiments to study the current density effect. Probably due to the influence of the skin perm-selectivity and the competition with H(+), increase in pH from 3 to 5 resulted in a significant increase in flux. Further increase in pH to 6 did not further increase the flux. The iontophoretic transport was found to increase linearly with concentration and current density, providing a convenient way to manage dose titration for Parkinson's disease therapy. Increase in concentration of NaCl dramatically reduced the flux of 5-OH-DPAT as a result of ion competition to the transport. When DHS was used, the iontophoretic transport was less. Also, with DHS the response in flux profile, by switching the current on and off, was shallower than that with HSC. With the optimum condition, a delivery of 104 microg of 5-OH-DPAT per cm(2) patch per hour is feasible, indicating that the therapeutic level could be achieved with a smaller patch size than required in case of rotigotine. Thus, based on this in vitro study, transdermal iontophoretic delivery of 5-OH-DPAT is very promising.     

Factorial design approach to evaluate interactions between electrically assisted enhancement and skin stripping for delivery of tacrine.

The objective of this work was to study the mechanisms of action of iontophoresis and electroporation and their interaction effects on delivery of tacrine hydrochloride in vitro across intact and stripped rat skin. Experiments were done according to a full factorial design, to quantify the effects of iontophoresis (X1), electroporation (X2) and stripped skin (X3) alone and in combination on cumulative drug delivery at 6 h. Mathematical model eliciting the main effects of the factors and their interaction on cumulative tacrine delivery in 6 h shows that all three techniques examined alone have a positive impact on the permeation of tacrine, the greatest enhancement in delivery achieved by iontophoresis. However, iontophoresis in combination with electroporation or skin stripping yielded no improvement in delivery compared to iontophoresis alone. The most significant enhancement is seen when all three methods of assisted delivery are done in combination. Iontophoresis appears to control drug delivery to the exclusion of other enhancement methods. Electroporation appears to cause formation of a large depot of tacrine in the skin.     

Transdermal delivery from a lipid sponge phase--iontophoretic and passive transport in vitro of 5-aminolevulinic acid and its methyl ester.

The hydrochloride salts of 5-aminolevulinic acid (ALA) and its methyl ester (m-ALA), respectively, were dissolved in a lipid sponge phase comprising monoolein, propylene glycol and aqueous buffer at concentrations of approximately 0.25% and 16% w/w m-ALA. The iontophoretic and passive delivery of ALA and m-ALA from this formulation through porcine skin in vitro were measured and compared to formulations used in clinical practice, 20% w/w ALA in Unguentum M and Metvix (a cream containing 16% w/w m-ALA). A sponge phase with 16% w/w m-ALA showed a higher passive flux (approximately 140 nmol cm(-2) h(-1) at 5 h) but a lower iontophoretic flux (approximately 800 nmol cm(-2) h(-1) at 5 h) compared to the clinically used products but the differences are hardly significant due to large standard deviations. ALA and m-ALA in sponge phase formulation showed iontophoretic fluxes in the range 80-100 nmol cm(-2) h(-1) at 3 h, i.e. values comparable to the passive fluxes from the more concentrated vehicles. The results demonstrate that the lipid sponge phase, a thermodynamically stable liquid with amphiphilic character, may have potential as a transdermal drug delivery vehicle.     

Transdermal drug delivery enhanced and controlled by erbium:YAG laser: a comparative study of lipophilic and hydrophilic drugs.

The influence of an erbium:YAG laser on the transdermal delivery of drugs across skin was studied in vitro. Indomethacin and nalbuphine, which have the same molecular weight, were selected as model lipophilic and hydrophilic drugs, respectively, to compare skin permeation by laser treatment. The results indicate a significant increase in the permeation of indomethacin and nalbuphine across skin pretreated with an erbium:YAG laser. The laser had a greater effect on the permeation of hydrophilic molecules which usually possess low permeability. The laser intensity and its spot size were found to play an important role in controlling transdermal delivery of drugs. Permeation of the hydrophilic drug increased following an increase of laser energy. On the other hand, a different result was observed for the lipophilic drug transported across laser-treated skin. The stratum corneum (SC) layer in skin could be partly ablated by the erbium:YAG laser. The barrier function of the SC may also be modulated by a lower intensity of the laser without affecting the viability and structure of the epidermis/dermis as determined by histological observations. However, ultrastructural alteration of the epidermis/dermis may be caused by laser treatment. Use of an erbium:YAG laser is a good method for enhancing transdermal absorption of both lipophilic and hydrophilic drugs, because it allows precise control of SC removal, and this ablation of SC can be reversible to the original normal status.     

Rate and extent of ion-exchange process: the effect of physico-chemical characteristics of salicylate anions.

Ten salicylate anions were used as model compounds in order to investigate systematically the impact of compound lipophilicity, valence, aqueous solubility and hydrogen bonding on binding into and release from a strong anion-exchange fiber, Smopex DS-218v. The release of salicylates from the fiber was studied at 1/10, 1/1 or 10/1 molar ratios of the external chloride-ions versus the salicylate bound in the fiber. The Donnan potential between the fiber and external solution (electrostatic interaction) appeared to be the main factor affecting the release of salicylates from the strong base anion-exchange fiber--an increase in the molar amount of the external chloride-ions resulted in a more effective release of all the salicylates from the fiber. The highest chloride-ion concentration (10/1) released the monovalent salicylates practically completely, while the lowest concentration (1/10) released only 10-35% of the loaded salicylates. The nature and strength of salicylate binding to the fiber by non-electrostatic interactions affected also the ion-exchange process, especially in dilute Cl- solutions. Hydrophobic interactions decreased the rate and amount of drug release from the fiber with the most lipophilic salicylates. Hydrogen bonding between the fiber and the compound restricted also the rate and extent of ion-exchange process of the hydrophilic 5-aminosalicylic acid and 5-hydroxysalicylic acid. The amount of divalent 5-carboxylsalicylic acid bound into and released from the fiber was clearly smaller as compared to the monovalent salicylates potentially due to cross-linking of the fiber chains.     

Spatially constrained localized transport regions due to skin electroporation.

Rapid, controlled molecular transport across human skin is of great interest for transdermal drug delivery and minimally invasive chemical sensing. Short, high-voltage pulses have been shown previously to create localized transport regions in the skin. Here, we show that these regions can be constrained to occur at specific sites using electrically insulating masks that restrict the field lines. The increase in total ionic and molecular transport per area was comparable to the levels observed in unconstrained electroporation of human skin. Constraining the area of intervention to encompass small areas of interest, a primary feature in the design of microdevices for transdermal drug delivery, can provide the same levels of flux as the unconstrained case.     

Lithium monitoring by reverse iontophoresis in vivo

BACKGROUND: We investigated reverse transdermal iontophoresis as an alternative, noninvasive method for lithium monitoring in vivo. The objectives of such an approach would be to facilitate compliance with treatment and to improve the quality of life for bipolar patients. METHODS: We studied 23 bipolar or schizo-affective patients. Over a 2-h period, we extracted lithium and other cations across intact skin by application of an electric current (0.8 mA) and quantified the concentrations by ion chromatography. A blood sample provided comparative reference values for the drug and other electrolytes. RESULTS: Lithium, sodium, potassium, and calcium were efficiently extracted by iontophoresis. Lithium extraction fluxes were proportional to the corresponding serum concentrations, whereas sodium, potassium, and calcium extraction fluxes were relatively constant, consistent with their stable concentrations in blood. Normalization of the lithium extraction flux with that of sodium, which acted as an "internal standard", permitted calibration of the monitoring procedure without the need for a blood measurement. This conclusion was tested retrospectively by dividing the patients into two groups. The reverse iontophoretic extraction data from the first subset (a) established the proportionality between lithium iontophoresis (or the relative electrotransport of lithium and sodium) and (b) predicted lithium blood concentrations in the second subset of patients. The predictive ability was very good, with the internal standard concept providing substantial benefit. CONCLUSIONS: Reverse iontophoresis appears to offer a novel and accurate method for lithium monitoring.     

Transdermal delivery of regular insulin to chronic diabetic rats: effect of skin preparation and electrical enhancement

The efficacy of passive transdermal versus electrically-enhanced, or iontophoretic delivery of insulin was studied. The effect of skin pre-treatment on iontophoretic delivery of insulin was also investigated. Rectangular pulses of 0.25 mA/cm² current amplitude, 2 kHz frequency, and 50% duty cycle were used as anodal stimulation for electrically enhanced transdermal delivery of insulin. Twenty (20) BB/Wor chronic diabetic adult male rats were shaved 48 h prior to the study, and some experimental groups had hair stubble removed with a depilatory lotion. The iontophoretic drug-containing electrode was filled with 3 ml of porcine regular insulin (100 IU/ml) which had been adjusted to an acidic pH of 3.68 using 0.1 M HCl. The iontophoretic electrodes were then adhered to the abdomen of the alert rat. Results of the iontophoretic procedure were quantified by monitoring changes in blood glucose levels. When insulin was placed on the shaved skin, blood glucose levels fell in the chronic diabetic rat. In general, glucose levels fell more quickly and more profoundly using an iontophoretic enhancement of transdermal insulin delivery. However, some skin preparations facilitated movement of insulin more efficiently. The most profound effect of lowered blood glucose occurred when a depilatory lotion was used on the day of the study in conjunction with iontophoresis, where blood glucose levels fell by 61% after 1 h of iontophoretic treatment. Results indicate that insulin was delivered passively at therapeutic levels when the skin had been treated with the depilatory lotion on the same day as the study, as measured through a reduction in blood glucose levels of 29% after 1 h of passive delivery. When the depilatory lotion was used 24 h prior to iontophoresis, blood glucose remained near initial blood glucose levels. In the groups that did not have the depilatory lotion applied, blood glucose levels fell by 8% after 1 h of iontophoretic insulin delivery. The experimental evidence indicates a substantial increase in the penetration of insulin with the same-day application of a depilatory lotion in conjunction with iontophoretic enhancement.     

Radiofrequency-driven skin microchanneling as a new way for electrically assisted transdermal delivery of hydrophilic drugs.

The aim of this study was to increase the skin penetration of two drugs, granisetron hydrochloride and diclofenac sodium, using a microelectronic device based on an ablation of outer layers of skin using radiofrequency high-voltage currents. These radiofrequency currents created an array of microchannels across the stratum corneum deep into the epidermis. The percutaneous penetration studies were first performed in vitro using excised full thickness porcine ear skin. An array of 100 microelectrodes/cm(2) was used in these studies. The skin permeability of both molecules was significantly enhanced after pretreatment with the radiofrequency microelectrodes, as compared to the delivery through the untreated control skin. Steady state fluxes of 41.6 micro g/cm(2)/h (r=0.997) and 23.0 micro g/cm(2)/h (r=0.989) were obtained for granisetron and diclofenac, respectively. The enhanced transdermal delivery was also demonstrated in vivo in rats. It was shown that diclofenac plasma levels in the pretreated rats reached plateau levels of 1.22+/-0.32 micro g/ml after 3 h to 1.47+/-0.33 micro g/ml after 6 h, as compared to 0.16+/-0.04 micro g/ml levels obtained after 6 h in untreated rats. Similarly, application of granisetron patches (3% in crosslinked hydrogel) onto rats' abdominal skin pretreated with radiofrequency electrodes resulted in an averaged peak plasma level of 239.3+/-43.7 ng/ml after 12 h, which was about 30 times higher than the plasma levels obtained by 24-h passive diffusion of the applied drug. The results emphasize, therefore, that the new transdermal technology is suitable for therapeutic delivery of poorly penetrating molecules.     

Intravenous nicotine retards transdermal absorption of nicotine: evidence of blood flow--limited percutaneous absorption.

For most drugs delivered by the transdermal route, percutaneous absorption is limited by the rate of release of the drug from the device or by diffusion across the stratum corneum. However, systemic absorption also requires that the drug be taken up by dermal blood vessels. As part of a bioavailability study of a transdermal delivery system, we observed that a concomitant intravenous infusion of nicotine had a marked effect on the absorption kinetics of transdermal nicotine. Plasma concentrations of nicotine rose less rapidly, reached a lower peak, and peaked at a later time, indicating delayed absorption of transdermal nicotine after intravenous nicotine versus after transdermal nicotine administered alone. Nicotine is known to produce cutaneous vasoconstriction. The likely explanation for our observation is that intravenous nicotine constricts dermal blood vessels, thereby limiting percutaneous absorption. Other vasoconstrictor drugs would be expected to retard the absorption of transdermal nicotine and perhaps other transdermal drugs as well.     

Delivery of nalbuphine and its prodrugs across skin by passive diffusion and iontophoresis.

The in vitro transport of nalbuphine (NA) and its prodrugs across various skins was investigated in order to assess the effects of prodrug lipophilicity on passive as well as iontophoretic permeation. The passive diffusion of NA and its prodrugs increased with the drug lipophilicity. Iontophoresis significantly increased the transport of NA and its prodrugs; the enhancement ratio was highest for NA and decreased as the drug lipophilicity increased. Measurements using intact and stratum corneum (SC)-stripped skins showed that the SC was the major skin diffusion barrier for the passive permeation of NA and nalbuphine pivalate (NAP). The iontophoretic permeation of NA and NAP across intact and SC-stripped skins indicated that the SC layer was not rate-limiting for the permeation of NA, but remained the rate-limiting barrier for transdermal permeation of NAP. Permeation studies using SC-stripped and delipidized skins suggested that the intercellular pathway was the predominant route for the passive permeation of NA and NAP as well as the iontophoretic permeation of NAP across the SC. The relative rates of passive and iontophoretic permeation across Wistar rat skins demonstrated that a significant amount of NA may permeate skin via the appendageal routes, whereas NAP permeated predominantly through the lipid matrix.     

Future drug delivery research in South Korea.

According to the Science Citation Index database, over 50 papers related to drug delivery have been published from South Korea during the last 3 years. For the purpose of this presentation, some of the recently carried out research in our department will be introduced and future research directions presented. Proliposomes are free flowing particles which are composed of drugs, phospholipids and a water soluble porous powder, and immediately form a liposomal dispersion upon hydration. The preparation can be stored sterilized in a dried state and, by controlling the size of the porous powder in proliposomes, relatively narrow range of reconstituted liposome size can be obtained. Because of these properties, proliposomes appear to be a potential alternative to liposomes in design and fabrication of liposomal dosage forms. Thus, we tested the feasibility of this preparation as a sustained transdermal dosage form. Proliposomes containing varying amount of nicotine, a model drug, were prepared using sorbitol and lecithin. Microscopic observation revealed that this preparation is converted to liposomes almost completely within minutes following contact with water. The release pattern of the model drug from this preparation was apparently similar to that of the Exodus((R)) patch, a commercially available transdermal nicotine formulation. Compared with nicotine powder, the nicotine flux across rat skin from proliposomes was initially retarded, and appeared to remain constant. This observation indicated that sustained transdermal delivery of nicotine is feasible using proliposomal formulations under occluded condition. In addition to the investigation of the potential application of proliposomes, we were also interested in the role of the stratum corneum (SC) in the enhanced delivery of drugs from liposomes. Thus, liposome-gel formulation containing hydrocortisone (HC), a model hydrophobic drug, was prepared and used in this study. The study was carried out on both normal and stratum corneum removed skins. Percutaneous absorption of HC across SC removed skin was significantly faster than that across normal skin, suggesting that SC behaves as a penetration barrier for the liposome-bound drugs. Interestingly, the liposome-gel in this study reduced the skin absorption of HC, compared with the conventional ointment formulation. The amount of HC absorbed from the liposome-gel after 8 h into the SC-removed skin was less than one third of that from the conventional ointment. Despite the reduced absorption, a higher and sustained skin concentrations of HC were achieved for the liposome-gel. Drug concentration in both viable and deep skin reached a maximum within 0.5 h. However, drug concentrations in these tissues declined as a function of time for conventional ointment, while those from the liposome-gel were greatly sustained, resulting in a 5-fold higher viable skin drug level was obtained at 8 h after the application. In contrast, plasma concentration of HC at 4 h from the liposome-gel was only one-fourth the value from the conventional ointment in the SC-removed skin. Therefore, the higher and sustained drug concentration in the viable skin appeared not to be due to the enhanced percutaneous absorption but due to retarded diffusion of the drug from the skin.     

基于STC12C5S60S2单片机经皮给药系统的设计

背景:经皮给药技术为蛋白质多肽类药物的导入提供了一种方便有效的方式。目的:研制一种基于微控制器的经皮给药系统,实现药物经皮无创导入的同时维持药物的活性,提高药物的生物利用度。方法:经皮给药系统以微控制器为核心,采用电致孔导入技术,电离导入技术和超声波导入技术从不同角度克服皮肤屏障,促进药物经皮吸收,在软硬件上合理的设计实现3种机制的协同作用,提高药物导入的效率。结果与结论:试制出经皮给药系统样机,该系统操作简便,以无创的方式经皮给药可以提高患者的依从性,通过各治疗参数的调节,可用于多种药物的经皮导入,为实现个体化治疗提供可能。