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ABSTRACT: Human and rodent solid tumors often exhibit elevated interstitial fluid pressure (IFP). This condition is recognized as a prognostic indicator for reduced responses to therapy and decreased disease-free survival rate. In the present study, we tested whether induction of a thermoregulatory-mediated increase in tissue blood flow, induced by exposure of mice to mild environmental heat stress, could influence IFP and other vascular parameters within tumors. Using several murine tumor models, we found that heating results in a sustained reduction in tumor IFP correlating with increased tumor vascular perfusion (measured by fluorescent imaging of perfused vessels, laser Doppler flowmetry, and MRI) as well as a sustained reduction in tumor hypoxia. Furthermore, when radiation therapy was administered 24 hours postheating, we observed a significant improvement in efficacy that may be a result of the sustained reduction in tumor hypoxia. These data suggest, for the first time, that environmental manipulation of normal vasomotor function is capable of achieving therapeutically beneficial changes in IFP and microvascular function in the tumor microenvironment.
Cancer Research 06/2011; 71(11):3872-80. · 7.86 Impact Factor
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ABSTRACT: Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.
Journal of Oncology 01/2010; 2010:396286.
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ABSTRACT: Despite an armamentarium that is wide in range, scope of action, and target, chemotherapy has limited success in colorectal cancer (CRC). Novel approaches are needed to overcome tumor barriers to chemotherapy that includes an abnormal tumor vasculature constituting a poor drug delivery system. We have previously shown that 5-methylselenocysteine (MSC) enhances therapeutic efficacy of irinotecan in various human tumor xenografts. We have recently demonstrated that MSC through vascular normalization leads to better tumor vascular function in vivo. In this study, we examined the role of MSC on tumor vasculature, interstitial fluid pressure (IFP) and drug delivery in 2 histologically distinct CRC xenografts, HCT-8 (uniformly poorly differentiated) and HT-29 (moderately differentiated tumor with avascular glandular regions). The presence of specific histologic structures as a barrier to therapy in these xenografts and their clinical relevance was studied using tissue microarray of human surgical samples of CRC. MSC led to a significant tumor growth inhibition, a reduced microvessel density, and a more normalized vasculature in both colorectal xenografts. While IFP was found to be significantly improved in HCT-8, an improved intratumoral doxorubicin delivery seen in both xenografts could explain the observed increase in therapeutic efficacy. Differentiated, glandular, avascular and hypoxic regions that contribute to tumor heterogeneity in HT-29 were also evident in the majority of surgical samples of CRC. Such regions constitute a physical barrier to chemotherapy and can confer drug resistance. Our results indicate that MSC could enhance chemotherapeutic efficacy in human CRC, especially in CRC with few or no hypoxic regions.
Clinical Colorectal Cancer 08/2009; 8(3):155-62. · 1.68 Impact Factor
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ABSTRACT: Anionic lipids like phosphatidylserine are known to significantly enhance electroporation mediated transepidermal transport of polar solutes of molecular weights up to 10kDa. The underlying mechanism of the effect of anionic lipids on transdermal transport is not fully understood. The main barrier to transdermal transport lies within the intercellular lipid matrix (ILM) of the stratum corneum (SC) and our previous studies indicate that dimyristoyl phosphatidylserine (DMPS) can perturb the packing of this lipid matrix. Here we report on our investigation on water retention in the SC following electroporation in the presence and the absence of DMPS. The water content in the outer most layers of the SC of full thickness porcine skin was determined using ATR-FTIR-spectroscopy. The results show that in the presence of DMPS, the SC remains in a state of enhanced hydration for longer periods after electroporation. This increase in water retention in the SC by DMPS is likely to play an important role in trans-epidermal transport, since improved hydration of the skin barrier can be expected to increase the partitioning of polar solutes and possibly the permeability.
International Journal of Pharmaceutics 03/2008; 350(1-2):138-44. · 3.35 Impact Factor
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ABSTRACT: Two major questions were addressed: (1) Can fever-range whole body hyperthermia (FR-WBH) affect the number of perfused tumor blood vessels? (2) Can pre-treatment with FR-WBH improve accumulation or anti-tumor efficacy of doxorubicin or DOXIL (liposomal doxorubicin)?
Perfused blood vessels were visualized by intravenous injection of the fluorescent dye (DiOC7(3)) and the number of labeled vessels in tumors and normal organs of unheated mice and those previously heated to 39.5 degrees C for 6 hours were compared. Using three animal tumor models (one syngeneic murine model and two human tumor xenografts in SCID mice) we also compared tumor growth and amount of intratumoral doxorubicin (given as free drug or as DOXIL) in control mice or those given pre-treatment with FR-WBH.
FR-WBH had no effect on the number of CD-31 labeled blood vessels. However, in tumors, but not in normal organs of the same animals, FR-WBH resulted in a significant increase in those blood vessels which could take up dye over a prolonged period of time after heating. There was also an increase in DOXIL uptake in the tumors of mice given FR-WBH prior to drug injection as well as enhanced therapeutic efficacy in all three tumor models.
FR-WBH increases the number of perfused blood vessels in tumors over a prolonged period following FR-WBH and thus may be useful for improving tumor targeting of cancer therapeutics. We discuss these data in relation to long-conserved thermoregulatory features in normal vasculature, which may be deficient in tumor vasculature.
International Journal of Hyperthermia 10/2007; 23(6):513-27. · 1.92 Impact Factor
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ABSTRACT: The resealing of porcine epidermis after electroporation is investigated. Porcine epidermis was subjected to electroporation (30 pulses at 100 V, 1 ms and at 1 Hz) in a vertical diffusion apparatus, in the presence of 2 mg/ml dimyristoylphosphatidylserine, to produce a long lasting permeable state. Resealing treatments include incubation in 0.0625-0.25 mM poloxamer 188 (P188), or incorporation of phosphatidylcholines (PC) and/or cationic lipids with additional pulses. The recovery of electric resistance of the epidermis samples after electroporation with or without resealing treatments was monitored. The transports of carboxyfluorescein and glucose were measured during the recovery process. Both P188 and PC were effective in resealing in terms of electric conductance and transport, with P188 reacting more rapidly and completely. P188 mediated lipid exchange between stratum corneum lipid particles was measured by fluorescence resonance energy transfer (FRET). Lipid reorganization facilitated by P188 and PC is suggested to be a major resealing mechanism of electroporation damage.
International Journal of Pharmaceutics 06/2007; 336(2):269-75. · 3.35 Impact Factor
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ABSTRACT: A lipid formulation consisting of 1,2-dimyristoyl-sn3-phosphatidylserine (DMPS) in a 0.2% sodium dodecylsulfate (SDS) solution was tested as an in vivo enhancer for the transcutaneous delivery of insulin. The formulation when applied to for 15 min was found to permeabilize porcine epidermis and prolong the permeable state as evidenced by electric resistance measurement. The formulation enhanced the transport of insulin through the epidermis by 40- to 100-fold, as compared to epidermis that was treated with SDS or DMPS alone. Application of electroosmosis across the formulation-treated epidermis enhanced the transport of insulin by an additional 10-fold. Pharmacokinetic studies were carried out in Sprague-Dawley rats. Transcutaneous delivery of insulin with formulation treatment and electroosmosis increased the plasma level of insulin by approximately 10-fold over delivery by formulation treatment alone. With the above protocol plasma insulin concentration remained relatively constant for up to 4h. The synergistic application of anionic lipid formulation and electroosmosis offers a promising non-invasive technique to deliver insulin transcutaneously.
International Journal of Pharmaceutics 01/2007; 326(1-2):1-6. · 3.35 Impact Factor
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ABSTRACT: Transdermal transport of insulin and extraction of interstitial glucose under anodal iontophoresis (electroosmosis) following electroporation in the presence of 1,2-dimyristoylphophatidylserine (DMPS) was studied. An earlier study showed that DMPS increased the transport of insulin across porcine epidermis under electroporation by approximately fourfold. It was suggested that DMPS increased the lifetime of electropores in the epidermis resulting in an enhanced transport of permeants. When electroosmosis was applied across the epidermis following electroporation with DMPS, the enhancement of insulin transport was approximately 18-fold over electroporation alone. When the same strategy was applied to extract interstitial glucose, the enhancement was approximately 23-fold over electroporation alone. Real-time transdermal insulin transport kinetics was measured using FITC-labeled insulin and a custom-made vertical diffusion apparatus that had a fluorescence cuvette as the receiver compartment. Insulin transport by electroporation alone showed a nonlinear kinetics that is most likely due to the resealing of the electropores with time. The transport kinetics when electroporation was carried out in the presence of DMPS was more linear, confirming earlier studies that suggested the DMPS stabilizes transport paths formed by electroporation. The data suggests that in vivo, noninvasive insulin delivery to therapeutic levels and glucose extraction may be achieved by combining electroporation with anionic lipids and electroosmosis.
Journal of Pharmaceutical Sciences 10/2006; 95(9):2041-50. · 3.06 Impact Factor
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ABSTRACT: The therapeutic activity and toxicity of drugs often depends on the accumulation of drugs in the peripheral anatomical compartment rather than the central compartment. In the routine practice of therapeutic drug monitoring (TDM) and pharmacokinetic studies, drug concentration determined by intermittent blood sampling is used as a surrogate for calculating the drug concentration in the peripheral compartment tissues. Microdialysis, a relatively less invasive procedure, has been used for estimation of free drug levels in dermal, subcutaneous and muscle tissues. Transcutaneous extraction of drugs from the dermal tissue is a good noninvasive alternative to phlebotomy and microdialysis. This requires a technique, which can facilitate the extraction of significant and reproducible amounts of drugs from the dermal extracellular fluid (ECF) within a short sampling duration. In the present work, we assessed the feasibility of electroporation and transcutaneous extraction (ETE) method for determining the time course of drugs in dermal ECF, using salicylic acid (SA) as a test drug. Electroporation protocol was optimized based on the in vitro diffusion studies of salicylic acid across rat skin. The concentration-time profile of total SA was determined in rats after a single i.v. bolus administration. The in vivo permeability coefficient (P(in vivo)) of rat skin was determined under steady state plasma concentration of drug created by i.v. bolus followed by constant rate infusion of SA. The pharmacokinetic parameters of the drug were determined using a two-compartment pharmacokinetic model. The theoretical predicted time course of free SA in the dermal ECF after a single i.v. bolus administration was calculated using standard formulae. The concentration of free SA determined by ETE is in good agreement with that calculated using two-compartment pharmacokinetic model. This study thus provides a credible evidence for the validity of ETE technique for determining the concentration of SA in the dermal ECF.
Journal of Controlled Release 07/2005; 105(1-2):132-41. · 5.73 Impact Factor
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ABSTRACT: The transdermal transport of cyclodextrins (CD) across porcine epidermis by electroporation was studied. Electroporation increased the permeation of beta-cyclodextrin (BCD) and hydroxy propyl beta-cyclodextrin (HPCD) by several orders of magnitude, relative to passive transport. The presence of BCD and HPCD enhanced the total transport of the test permeants piroxicam and carboxyfluorescein (CF), respectively, from both permeant solutions and suspensions. BCD enhanced the fraction of piroxicam transported across the epidermis into the receiver compartment medium. This was most likely due to the prolonged post-pulse permeability state of the epidermis. The fraction of CF retained in the epidermis was increased by HPCD. The rate of diffusion of CF from epidermis into the receiver compartment was decreased by the presence of HPCD, apparently due to the aggregate forming tendency of HPCD. The in vivo delivery of CF by electroporation in mice demonstrated the potential of HPCD for sustaining the transdermal absorption rate of hydrophilic molecules.
Journal of Controlled Release 11/2004; 99(3):393-402. · 5.73 Impact Factor
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ABSTRACT: The objective of the experiment was to study the influence of sodium dodecyl sulfate (SDS) on transdermal transport of diffusants by electroporation. The resistance of porcine epidermis in contact with SDS solution (0.2% w/v) dropped by 40% within 24 h. SDS improved the efficiency of transdermal delivery of glucose, dextrans of molecular weight (MW) 4 kDa (FD4K) and 10 kDa (FD10K) by electroporation. However, the transport of dextran MW 35 kDa (FD35K) was not influenced significantly. Pretreatment of epidermis with SDS solution reduced its electroporation threshold from 80 to 60 V. It appears that presence of SDS during electroporation helps in achieving the desired transport with less electrical exposure dose. SDS enhanced the transdermal delivery of molecules by electroporation most likely by facilitating the barrier disruption during pulse application and also by prolonging the lifetime of electropores created by the pulse.
Journal of Controlled Release 09/2004; 98(2):307-15. · 5.73 Impact Factor
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ABSTRACT: The influence of temperature on the electrical conductance and transport of macromolecules across porcine epidermis during and after electroporation were studied. The passive diffusion of fluorescein isothiocyanate labeled dextran (molecular weight 10 kDa, FD10K), across the epidermis did not differ much at temperatures below 37 degrees C, but became significantly higher above 40 degrees C. The resistance drop during pulse application was less sensitive to temperature within the temperature range (10-50 degrees C) of this study. The kinetics of decrease in postpulse conductance of the electroporated epidermis was fit to a monoexponential function. The rate of decrease in postpulse conductance was significantly less and FD10K transport was markedly high at temperature over 40 degrees C relative to those observed at temperatures less than 37 degrees C. This jump in transport cannot be explained by electrophoresis induced by the pulse, or by the increased diffusion kinesis of the molecules. The enhanced transport is most likely due to the prolonged postpulse permeable state of the skin. Electroporation at mild hyperthermia temperatures resulted in delivering much higher quantities of macromolecules.
Journal of Pharmaceutical Sciences 05/2004; 93(4):908-15. · 3.06 Impact Factor
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ABSTRACT: The pH dependence of porcine epidermis permeability and the influence of pH on the electroporation transport of molecules were studied. The resistance was maximum at pH 5 and decreased with an increase or decrease in the pH of the donor medium. The permeability coefficient of glucose was significantly higher at pH 7.5, compared to pH 5. On electroporation, the resistance recovery rate of porcine epidermis was rapid below pH 5 and slower at above pH 7.5. The transport studies revealed that a donor medium pH above 7.5 helps to maintain the postpulse permeability state of the skin. By changing the donor medium pH from 5 to 7.5, the postpulse transport of glucose and fluorescein isothiocyanate (FITC)-labeled dextran (MW 10 kDa) (FD10K) was enhanced by about threefold. The lipids extracted from porcine epidermis showed pI values of 4.3 and 5.9. Vesicles of these lipids fused more rapidly at pH 5 than at pH 3, 7, and 10. The results imply that pH-sensitive postpulse resistance recovery and molecular transport are due to the charge states of epidermal lipids.
Journal of Controlled Release 12/2003; 93(1):49-57. · 5.73 Impact Factor
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ABSTRACT: A heat-sensitive liposomal drug delivery system was tested using Colon-26 (CT-26) cultured cells and tumors in mice. Lucifer yellow iodoacetamide (LY) was used as a fluorescence marker. The heat-sensitive liposomes exploit the temperature-dependence of critical micellar concentrations of the poloxamer, F127. LY release from unilamellar liposomes at different temperatures was measured. Onset of LY release occurred near 33 degrees C, and reached plateau above 42 degrees C when 90% of the LY was released. Temperature-treated liposomes were mixed with CT-26 cells to measure the binding of the released LY to cell surface. Temperature-dependency of cell-bound LY corresponds to the release curve. CT-26 tumors were grown subcutaneously in both hind legs of Balb/c mice. Mice received heat-sensitive or plain liposomes via tail vein injections, or no liposomes. For each mouse, one tumor was kept at 31.5 degrees C, while the counterlateral tumor was heated to 42 degrees C during injection and for 30min after. LY released in tumors was determined from fluorescence intensity. Tumors receiving heat-sensitive liposomes plus heat treatment showed 2.5-fold greater fluorescence than all other tumors, which were at the background level. This study demonstrates the possible use of poloxamer-containing liposomes as a heat-sensitive drug delivery system in vivo.
International Journal of Pharmaceutics 09/2003; 261(1-2):105-14. · 3.35 Impact Factor
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ABSTRACT: Anionic phospholipids, but not cationic or neutral phospholipids, were found to enhance the transdermal transport of molecules by electroporation. When added as liposomes to the milieus of water-soluble molecules to be delivered through the epidermis of porcine skin by electroporation, these phospholipids enhance, by one to two orders of magnitude, the transdermal flux. Encapsulation of molecules in liposomes is not necessary. Dimyristoylphosphatidylserine (DMPS), phosphatidylserine from bovine brain (brain-PS), dioleoylphosphatidylserine (DOPS), and dioleoylphosphatidylglycerol (DOPG) were used to test factors affecting the potency of anionic lipid transport enhancers. DMPS with saturated acyl chains was found to be a much more potent transport enhancer than those with unsaturated acyl chains (DOPS and DOPG). There was no headgroup preference. Saturated DMPS was also more effective in delaying resistance recovery after pulsing, and with a greater affinity in the epidermis after pulsing. Using fluorescent carboxyl fluorescein and fluorescein isothiocyanate (FITC)-labeled Dextrans as test water-soluble molecules for transport, and rhodamine-labeled phospholipids to track anionic phospholipids, we found, by conventional and confocal fluorescence microscopy, that transport of water-soluble molecules was localized in local transport spots or regions (LTRs) created by the electroporation pulses. Anionic phospholipids, especially DMPS, were located at the center of the LTRs and spanned the entire thickness of the stratum corneum (SC). The degree of saturation of anionic phospholipids made no difference in the densities of LTRs created. We deduce that, after being driven into the epidermis by negative electric pulses, saturated anionic phospholipids mix and are retained better by the SC lipids. Anionic lipids prefer loose layers or vesicular rather than multilamellar forms, thereby prolonging the structural recovery of SC lipids to the native multilamellar form. In the presence of 1 mg/ml DMPS in the transport milieu, the flux of FITC-Dextran-4k was enhanced by 80-fold and reached 175 microg/cm(2)/min. Thus, the use of proper lipid enhancers greatly extends the upper size limit of transportable chemicals. Understanding the mechanism of lipid enhancers enables one to rationally design better enhancers for transdermal drug and vaccine delivery by electroporation.
Biophysical Journal 11/2002; 83(4):2064-73. · 3.65 Impact Factor
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ABSTRACT: Transdermal insulin transport by electroporation was measured using porcine epidermis and fluorescein-labeled insulin. Previous studies have shown that anionic lipids can enhance the electroporative transport of molecules up to 10 kDa in size. It was also shown that it is the charge and not the type of the phospholipid head group that influences transdermal transport under electroporation. Moreover, phospholipids with saturated acyl chains enhance the transport of larger molecules more as compared to those with unsaturated chains. In the current study, based on those earlier findings, the effect of 1,2-dimyristoyl-3-phosphatidylserine (DMPS) on the transdermal transport of insulin by electroporation was examined. Porcine epidermis was used as a model for skin. Transport was measured using glass vertical diffusion apparatus in which the epidermis separated the donor and receiver compartments. Negative pulses were applied across the epidermis using platinum electrodes. Results show that when electroporation was carried out in the presence of DMPS, there was greater than 20-fold enhancement of insulin transport. Furthermore, while in the presence of the phospholipid, almost all the transported insulin was detected in the receiver compartment; in the absence of added lipids, only about half the insulin transported was in the receiver compartment and an almost equal amount of insulin remained in the epidermis. Fluorescence microscopy revealed that the insulin transport was mainly through the lipid multilayer regions that surround the corneocytes.
Biochimica et Biophysica Acta 09/2002; 1564(1):5-8. · 4.66 Impact Factor
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ABSTRACT: Transdermal drug delivery is an attractive approach for either local or systemic treatment in medicine. In the last decade, different active transdermal delivery methods have been further investigated such as cationic liposomal delivery and electroporation-enhanced delivery. In light of gaining a synergistic effect of lipid and electroporation, a new method of using anionic lipids to enhance the transdermal transport of molecules under electroporation is reported here. Heat-stripped porcine epidermis was used for measurement of transdermal transport using an in vitro vertical diffusion apparatus. Lipid vesicles were prepared using a 1:1 mole ratio mixture of 1,2-dioleoyl-3-phosphatidylglycerol (DOPG) and 1,2-dioleoyl-3-phosphatidylcholine (DOPC). When the lipids were mixed with (but not encapsulating) the transport target molecule, the electroporation-induced transport through porcine epidermis was increased as compared to that without the lipids. The enhancement in transport was dependent upon the size and the charge of the transported molecule. Methylene blue (MB), protoporphyrin IX (PpIX) and dimethyl-protoporphyrin IX (DM-PpIX) were used as small target molecules, and FITC-dextrans (4 to 155 kDa) were used as large target molecules in our studies. Enhancement of transport, to varying degree, was observed for all three small molecules (molecular weights <1 kDa), in the presence of DOPG:DOPC vesicles. In the case of large molecules, lipid-enhanced transport was only observed for the 4 kDa dextran, and not for the larger ones (M(w)>10 kDa). Neutral or cationic lipids alone did not enhance the transdermal transport under the electroporation conditions we used.
Journal of Controlled Release 08/2002; 82(2-3):399-405. · 5.73 Impact Factor
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ABSTRACT: The temperature sensitive properties of Pluronic F-127 (MW approximately 12600, PEO(98)-PPO(67)-PEO(98)), a block co-polymer or poloxamer, was used to control liposome-cell adhesion. When associated with liposomes, the PEO moiety of the block co-polymer is expected to inhibit liposome-cell adhesion. Liposomes were made using egg phosphatidylcholine and different mole% of Pluronic F-127. Size measurement of the liposomes at different temperatures, in the presence and absence of Pluronic F-127, shows significant reduction in the size of multilamellar vesicles, at higher temperatures, by the Pluronic molecules. Negative stain electron microscopy study showed the presence of individual molecules and micelles of Pluronic, respectively at temperatures below and above the critical micellar temperature (CMT). Measurement of the surface associated Pluronics indicated that they associated with liposomes when the sample was heated above the Pluronic CMT, and dissociated from liposomes when cooled below the CMT. Attachment of the Pluronic containing liposomes to CHO cells was inhibited at temperatures above the CMT, but not at temperatures below CMT, indicating that temperature-sensitive control of liposome-cell adhesion is achieved.
Biochimica et Biophysica Acta 03/2002; 1559(1):32-42. · 4.66 Impact Factor
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ABSTRACT: The mechanism of high-voltage pulse-induced permeabilization of the stratum corneum, the outer layer of the skin, is still not completely understood. It has been suggested that joule heating resulting from the applied pulse may play a major role in disrupting the stratum corneum. In this study, electrical and ultrastructural measurements were conducted to examine the temperature dependence of the pulse-induced permeabilization of the stratum corneum. The stratum corneum resistance was measured using a vertical diffusion holder, with the stratum corneum placed between two electrode-containing chambers. The stratum corneum resistance was reduced manyfold during the applied pulse. The extent of resistance reduction increased with pulse voltage until reaching a threshold value, above which the resistance reduction was less dependent on the pulse voltage. The stratum corneum was more susceptible to permeabilization at high temperature, the threshold voltage being lower. The stratum corneum resistance recovered within milliseconds after a single 0.3-ms pulse. High-temperature samples had a more prolonged recovery time. Using time-resolved freeze fracture electron microscopy, aggregates of lipid vesicles were observed in all samples pulsed above the threshold voltage. The sizes and fractional areas occupied by aggregates of lipid vesicles at 4 degrees C and at 25 degrees C were measured at different time points after the applied pulse. Aggregates of vesicles persisted long after the electric resistance was recovered. After pulsing at the same voltage of 80 V, samples at 4 degrees C were found to have slightly more extensive aggregate formation initially, but recovered more rapidly than those at 25 degrees C. The more rapid recovery of the 4 degrees C samples was likely due to a lower supra-threshold voltage. Viscoelastic instability propagation created by the pulse may also play a role in the recovery of the aggregates.
Biophysical Journal 02/2002; 82(1 Pt 1):109-19. · 3.65 Impact Factor
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ABSTRACT: The objective of the experiment was to study the influence of sodium dodecyl sulfate (SDS) on transdermal transport of diffusants by electroporation. The resistance of porcine epidermis in contact with SDS solution (0.2% w/v) dropped by 40% within 24 h. SDS improved the efficiency of transdermal delivery of glucose, dextrans of molecular weight (MW) 4 kDa (FD4K) and 10 kDa (FD10K) by electroporation. However, the transport of dextran MW 35 kDa (FD35K) was not influenced significantly. Pretreatment of epidermis with SDS solution reduced its electroporation threshold from 80 to 60 V. It appears that presence of SDS during electroporation helps in achieving the desired transport with less electrical exposure dose. SDS enhanced the transdermal delivery of molecules by electroporation most likely by facilitating the barrier disruption during pulse application and also by prolonging the lifetime of electropores created by the pulse.
Journal of Controlled Release.
