Biomedical subjects

Jagdish Singh

Publications and source records attributed to Jagdish Singh.

At least 19 recordsLinked to original sources

PubMed2006

Phase-sensitive polymer-based controlled delivery systems of leuprolide acetate: in vitro release, biocompatibility, and in vivo absorption in rabbits.

Leuprolide acetate (LA) is a synthetic analog of gonadotropin releasing hormone. It is effective in prostate cancer treatment only when its desired concentration in blood is maintained for longer duration. Therefore, the purpose of this study was to investigate the in vitro release, biocompatibility, and in vivo absorption of LA from phase-sensitive polymer delivery systems capable of delivering it at a controlled rate for longer duration. Phase-sensitive formulations were prepared by dissolving dl-polylactic acid (dl-PLA) in a mixture of organic solvents, benzyl benzoate (BB) and benzyl alcohol (BA). LA was incorporated into the polymer solution by homogenization. In vitro release was studied into 15 ml of releasing media contained in a vial which was maintained at 37 degrees C in a reciprocal shaking water bath. The amount of LA in the released samples was analyzed by stability indicating HPLC method. The biocompatibility of polymer formulations was investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo absorption of LA from delivery systems was studied in rabbits. Blood samples were analyzed for LA and testosterone contents by commercially available immunoassay kits. In vitro release studies showed a greater release of LA from formulations containing a greater proportion of BA (hydrophilic fraction) in the solvent mixture. In vitro biocompatibility study showed significantly (p<0.05) higher cell viability in growth media diluted with polymer extract than the control. In vivo absorption of LA and its effect on testosterone level in rabbits from the delivery system showed a sustained plasma level of LA up to 12 weeks which suppressed the testosterone plasma concentration to castration level beginning from 14th day until 90 days. Thus, phase-sensitive polymer delivery systems of LA were biocompatible and delivered LA at a controlled rate both in vitro and in vivo to keep testosterone plasma concentration at a castration level up to 3 months.

Animals↗

PubMed2006

Poly lactic acid based injectable delivery systems for controlled release of a model protein, lysozyme.

The objective of this study was to evaluate the critical formulation parameters (i.e., polymer concentration, polymer molecular weight, and solvent nature) affecting the controlled delivery of a model protein, lysozyme, from injectable polymeric implants. The conformational stability and biological activity of the released lysozyme were also investigated. Three formulations containing 10%, 20%, and 30% (w/v) poly lactic acid (PLA) in triacetin were investigated. It was found that increasing polymer concentration in the formulations led to a lower burst effect and a slower release rate. Formulation with a high molecular weight polymer showed a greater burst effect as compared to those containing low molecular weight. Conformational stability and biological activity of released samples were studied by differential scanning calorimeter and enzyme activity assay, respectively. The released samples had significantly (P < 0.05) greater conformational stability and biological activity in comparison to the control (lysozyme in buffer solution kept at same conditions). Increasing polymer concentration increased both the conformational stability and the biological activity of released lysozyme. In conclusion, phase sensitive polymer-based delivery systems were able to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over an extended period.

Anti-Infective Agents↗

PubMed2006

Prospects for vaccines for allergic and other immunologic skin disorders.

The human skin hosts a variety of immune response-associated components that together form the skin immune system. Any abnormality in the functioning of the skin immune system leads to a variety of dermatologic complications, including dermatitis, psoriasis, and eczema. Exposure to antigens/allergens can lead to allergic skin disorders such as atopic dermatitis, urticaria, and allergic contact dermatitis. Recent investigations have provided new insights into the immunologic processes leading to the development of skin diseases. T cells play a central role in the activation and regulation of immune responses by recognizing antigen and inducing cytokine production. Despite advances in the understanding of the immunologic events leading to the development of skin diseases, no effective prevention measure exists. Current therapeutic treatments are based on either alleviating the symptoms or suppressing the immune system with immunosuppressive drugs. Allergen-specific immunotherapy is expected to induce specific T cells that abolish allergen-induced proliferation of T helper cells, as well as their cytokine production. Recent approaches using recombinant protein, polycytosine guanine oligonucleotides, and plasmid DNA for vaccination suggest the possibility of protection against these skin disorders. The involvement of T cells in psoriasis indicates that the development of a T-cell receptor peptide vaccine may be beneficial. Dendritic cell-based vaccines using tolerogenic dendritic cells that can induce T-cell tolerance have been shown to be useful in dealing with autoimmune disorders and allergic conditions. In the light of these developments, this article presents the current status and prospects of developing vaccines for allergic and other immunologic skin disorders.

Humans↗

PubMed2005

Skin targeted DNA vaccine delivery using electroporation in rabbits II. Safety.

The Achilles heel of gene-based therapy is gene delivery into the target cells efficiently with minimal toxic effects. Viral vectors for gene/DNA vaccine delivery are limited by the safety and immunological problems. Recently, nonviral gene delivery mediated by electroporation has been shown to be efficient in different tissues including skin. There are no detailed reports about the effects of electroporation on skin tissue, when used for gene/DNA vaccine delivery. In a previous study we demonstrated the efficacy of skin targeted DNA vaccine delivery using electroporation in rabbits [Medi, B.M., Hoselton, S., Marepalli, B.R., Singh, J., 2005. Skin targeted DNA vaccine delivery using electroporation in rabbits. I. Efficacy. Int. J. Pharm. 294, 53-63]. In the present study, we investigated the safety aspects of the electroporation technique in vivo in rabbits. Different electroporation parameters (100-300 V) were tested for their effects on skin viability, macroscopic barrier property, irritation and microscopic changes in the skin. Skin viability was not affected by the electroporation protocols tested. The electroporation pulses induced skin barrier perturbation and irritation as indicated by elevated transepidermal water loss (TEWL) and erythema/edema, respectively. Microscopic studies revealed inflammatory responses in the epidermis following electroporation using 200 and 300 V pulses. However, these changes due to electroporation were reversible within a week. The results suggest that the electroporation does not induce any irreversible changes in the skin and can be a useful technique for skin targeted DNA vaccine delivery.

Animals↗

PubMed2005

Preparation, in vitro release, in vivo absorption and biocompatibility studies of insulin-loaded microspheres in rabbits.

The purpose of this study was to develop a single-dose insulin delivery system based on poly (lactide-co-glycolide) (PLGA) microspheres to provide basal insulin level for a prolonged period. Insulin-loaded PLGA microspheres were prepared by water-in-oil-in-water double emulsion (batch A) and solid-in-oil-in-water emulsion (batch B) methods. Microspheres were characterized for physical characteristics and in vitro release. In vivo absorption of insulin and biocompatibility of insulin-loaded PLGA microspheres were performed in diabetic New Zealand white rabbits. Light and transmission electron microscopy were performed on the skin tissues excised from microspheres injected sites in order to study the biocompatibility. The burst release of insulin was high (47%) from batch B and low (5%) from batch A. Therefore, we mixed microspheres of batch A and B in ratio of 3:1 w/w, which produced desirable in vitro release profile. In vivo absorption study showed that insulin-loaded microspheres provided a serum insulin level of 20-40 microU/ml up to 40 days. Biocompatibility study provided evidence of normal inflammatory and foreign body reactions, which were characterized by the presence of macrophages, fibroblasts and foreign body giant cells. Neither necrosis nor tissue damage was identified. At the end of 12 weeks, no distinct histological differences were observed in comparison to the control tissue samples. In conclusion, insulin-loaded PLGA microspheres controlled the in vivo absorption of insulin to maintain the basal insulin level for longer period and the delivery system was biocompatible.

Animals↗

PubMed2005

In vitro release of insulin and biocompatibility of in situ forming gel systems.

The purpose of this study was to develop single-dose insulin delivery system based on in situ forming gel to provide basal insulin level for a prolonged period. The in situ forming gel formulation was prepared by dissolving poly(d,l-lactic acid) (PLA) in hydrophobic (benzyl benzoate) and hydrophilic (benzyl alcohol) solvent mixtures. In vitro release was carried out in phosphate buffered saline (PBS) (pH 7.4) and the amount of released insulin was quantified by MicroBCA assay. In vivo biocompatibility study of in situ forming gel system was based on the histological evaluation of the tissue samples retrieved from injection sites at different time points. The tissue reaction was evaluated over 12 weeks. Throughout this period, all formulations showed normal inflammatory and foreign body reactions characterized by the presence of macrophages, fibroblasts and foreign body giant cells. Neither necrosis nor tissue damage could be identified. At the end of 12 weeks, no distinct histological differences were observed in comparison to the control tissue samples. The comparable results between blank and insulin-loaded in situ forming gel system indicated that the insulin itself did not induce additional inflammatory reactions. The results suggested that in situ forming gel system was biocompatible.

Absorbable Implants↗

PubMed2005

Effects of ionization and penetration enhancers on the transdermal delivery of 5-fluorouracil through excised human stratum corneum.

The purpose of this study was to determine the effects of ionization and penetration enhancers on the transdermal delivery of 5-fluorouracil (5-FU) through excised human stratum corneum. The in vitro transport of 5-FU was determined at three physiologically relevant pH values of 5.0, 7.4 and 8.0, and in the presence of suitable penetration enhancers, namely Azone (AZ), lauryl alcohol (LA), and isopropyl myristate (IPM). The results showed that passive permeation of 5-FU is dependent upon the pH of the donor solution, although did not fully conform to the pH-partition hypothesis. A further analysis of data suggested an inverse relationship (i.e., negative correlation) between steady-state flux and aqueous solubility of 5-FU at these pH values (correlation coefficient = -0.4205), although correlation was not statistically significant (p = 0.7237). In the absence of a penetration enhancer, the in vitro permeability of 5-FU was quite low (0.82+/-0.06 x 10(4) cm/h). This delivery rate was enhanced by approximately by 3, 4 and 24-fold, respectively, when IPM, LA, and AZ were incorporated into the donor solution. All these enhancements were statistically significant (p < 0.05) compared to control, and occurred regardless of the polarity (solubility parameters) of these enhancers. Out of three examined enhancers, AZ appears to be a suitable enhancer for enhancing transport of 5-FU, which merits in vivo investigation in a suitable animal model. Possible mechanisms of enhancement by these penetration enhancers are also discussed.

Administration, Cutaneous↗

PubMed2005

Controlled delivery of testosterone from smart polymer solution based systems: in vitro evaluation.

The objective of this research is to develop injectable polymers solution based controlled release delivery systems for testosterone (TSN), using phase sensitive and thermosensitive polymers. A combination of poly(lactide) (PLA) and solvents mixture of benzyl benzoate (BB) and benzyl alcohol (BA) was used in the phase sensitive polymer delivery system. The effects of solvents system and drug loading on the in vitro TSN release were evaluated. In the case of thermosensitive polymer delivery systems, a series of low-molecular-weight poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with varying ratio of lactide/glycolide (LA/GA, 2.0-3.5) were studied to control the release of TSN. The effects of varying block length of copolymers 1-4 on the in vitro TSN release were evaluated. Phosphate buffer saline (pH 7.4) containing 0.5% (w/v) Tween-80 was used as in vitro release medium. The amount of the released TSN was determined by an HPLC method. A controlled (zero-order) in vitro release of TSN was observed from both the phase sensitive and thermosensitive polymer delivery systems. Addition of BA (15%, v/v) in solvents system significantly (p<0.05) increased the release rate of TSN (0.33+/-0.01 mg/ml) from phase sensitive delivery system in comparison to solvent without BA (0.27+/-0.00 mg/day). Increasing drug loading also increased release rate. In the case of thermosensitive polymer delivery system, increasing the hydrophobic PLGA block length of copolymers significantly (p<0.05) decreased the release rate of TSN. It is evident from this study that the phase sensitive and thermosensitive polymers are suitable for developing prolong-release injectable implant delivery systems for TSN.

Drug Delivery Systems↗

PubMed2005

Skin targeted DNA vaccine delivery using electroporation in rabbits. I: efficacy.

Genetic immunization through skin is highly desirable as skin has plenty of antigen presenting cells (APCs) and is easily accessible. The purpose of this study was to investigate the effects of electroporation pulse amplitude, pulse length and number of pulses on cutaneous plasmid DNA vaccine delivery and immune responses, following intradermal injection in vivo in rabbits. Expression of the delivered plasmid was studied using a reporter plasmid, coding for beta-galactosidase. The efficiency of DNA vaccine delivery was investigated using a DNA vaccine against Hepatitis B, coding for Hepatitis B surface antigen (HBsAg). Serum samples and peripheral blood mononuclear cells (PBMC) were analyzed for humoral and cellular immunity, respectively, following immunization. The expression of transgene in the skin was transient and reached its peak in 2 days post-delivery with 200 and 300 V pulses. The expression levels with 200 and 300 V pulses were 48- and 129-fold higher, respectively, compared with the passive on day 2. In situ histochemical staining of skin with X-gal demonstrated the localized expression of beta-galactosidase with electroporation pulses of 200 and 300 V. Electroporation mediated cutaneous DNA vaccine delivery significantly enhanced both humoral and cellular immune responses (p<0.05) to Hepatitis B compared to passive delivery. The present study demonstrates the enhanced DNA vaccine delivery to skin and immune responses by topical electroporation. Hence, electroporation mediated cutaneous DNA vaccine delivery could be developed as a potential alternative for DNA vaccine delivery.

Animals↗

PubMed2005

Effect of chemical penetration enhancer and iontophoresis on the in vitro percutaneous absorption enhancement of insulin through porcine epidermis.

The purpose of this study was to investigate the effect of chemical enhancers (fatty acids and limonene) and iontophoresis on the in vitro permeability enhancement of insulin through porcine epidermis. The following fatty acids were used: palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3). Franz diffusion cells and the Scepter iontophoretic power source were used for the percutaneous absorption studies. Cathodal iontophoresis was performed at 0.2 mA/cm2 current density. Iontophoresis in combination with chemical enhancers synergistically increased (p<0.05) the in vitro permeability of insulin. Linolenic acid (C18:3) produced greater permeability of insulin through epidermis than did other fatty acids during passive (44.45 x 10(-4) cm/h) and iontophoretic (78.03 x 10(-4) cm/h) transport. Lispro insulin flux was significantly (p<0.05) greater through linolenic acid and limonene pretreated epidermis compared to untreated controls during both passive and iontophoretic transports. Using limonene as a penetration enhancer, a linear increase in the passive and iontophoretic flux of lispro insulin was observed with donor concentrations increasing from 100 IU/mL to 300 IU/mL. Iontophoretic flux through limonene-treated epidermis using 0.5 mA/cm2 current density and 300 IU/mL insulin donor solution was 45.63 IU/cm2/day. Using an iontophoretic patch size of 10 cm2, we would be able to deliver 50 IU of insulin within 3 h.

Administration, Cutaneous↗

PubMed2005

In vitro release of levonorgestrel from phase sensitive and thermosensitive smart polymer delivery systems.

The objective of this research is to develop injectable controlled delivery systems for the contraceptive hormone, levonorgestrel (LNG), using phase sensitive and thermosensitive polymers. A combination of poly (lactide) (PLA) and a solvent mixture of benzyl benzoate (BB) and benzyl alcohol (BA) was used in the phase-sensitive polymer delivery systems. The effects of solvent systems and polymer concentrations on the in vitro LNG release were evaluated. In the case of thermosensitive polymer delivery systems, a series of low-molecular-weight poly (lactide-co-glycolide)-poly (ethylene glycol)-poly (lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with varying ratios of lactide/glycolide (LA/GA, 2.0-3.5) were used. The effects of varying block length of copolymers 1, 2, 3, and 4 on the in vitro LNG release were evaluated. Phosphate buffer saline (pH 7.4) containing 0.5% w/v Tween-80 was used as in vitro release medium. The amount of the released LNG was determined by an high pressure liquid chromatography (HPLC) method. A controlled (zero-order) in vitro release of LNG was observed from both phase-sensitive and thermosensitive-polymer delivery systems. Increasing the concentration of the phase-sensitive polymer from 5% to 30% significantly (p < 0.05) decreased the release rate of LNG from 38.32 microg/day to 31.45 microg/day; and increasing the hydrophilic fraction of the solvents mixture (i.e., BA) significantly (p < 0.05) increased the release rate of LNG. In the case of the thermosensitive polymer delivery system, increasing the hydrophobic PLGA block length of copolymers significantly (p < 0.05) decreased the release rate of LNG (98.65 microg/day to 67.60 microg/day). It is evident from this study that both the phase sensitive and thermosensitive polymers are suitable for developing prolonged-release injectable delivery systems for the contraceptive hormone.

Benzoates↗

PubMed2004

Triblock copolymers: synthesis, characterization, and delivery of a model protein.

The purpose of this study was to synthesize and characterize biodegradable and thermosensitive triblock copolymers for delivering protein at controlled rate in biologically active form for longer duration of time. A series of thermosensitive triblock copolymers with different block lengths (PLGA-PEG-PLGA) were synthesized by ring-opening polymerization of d,l-lactide and glycolide with polyethylene glycol (PEG) in the presence of stannous octoate. Compositions and molecular weight of triblock copolymers were characterized by 1H NMR spectrometry and gel permeation chromatography, respectively. A single test-tube inverting method was employed to determine the sol-gel transition temperature. Lysozyme was used as a model protein. Lysozyme solution formulation was prepared with different triblock copolymers for in vitro release. Lysozyme concentration and its biological activity in the released sample were determined using a standard MicroBCA method and bacterial cell lysis method, respectively. The effects of varying block lengths and concentrations of copolymers on the in vitro release of lysozyme were evaluated. The release profiles from formulations showed a higher initial release followed by slower release up to 4 weeks. Increasing the block lengths of copolymers decreased burst release of lysozyme from 41.2+/-5.4% to 16.1+/-3.9%. Increasing copolymer concentrations decreased the drug release. Lysozyme in the 4 weeks released samples retained most of its biological activity (>80%). It is feasible to deliver protein in biologically active form for longer duration by varying block lengths and concentrations of triblock copolymers.

Animals↗

PubMed2004

Controlled release of a model protein lysozyme from phase sensitive smart polymer systems.

The purpose of this study was to investigate the suitability of phase sensitive smart polymer-based protein formulations in order to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over extended period of time. Four different formulations, using D,L-poly(lactide) (D,L-PLA) and a solvent mixture of different ratios of benzyl benzoate (BB) and benzyl alcohol (BA), were prepared. Conformational stability and biological activity of lysozyme were studied by differential scanning calorimeter and enzyme activity assay, respectively. We found a significant (P < 0.05) increase in burst and rate of release of incorporated lysozyme from formulations containing greater proportion of BA. In order to increase the conformational stability and biological activity of lysozyme, we incorporated mannitol as stabilizer into formulations. Mannitol increased the conformational and biological activity of lysozyme in comparison to the control formulation prepared without mannitol. In conclusion, phase sensitive smart polymer-based delivery systems were able to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over extended period of time.

Benzoates↗

PubMed2004

Iontophoretic enhancement of leuprolide acetate by fatty acids, limonene, and depilatory lotions through porcine epidermis.

The effect of chemical enhancers (e.g., fatty acids, limonene, depilatory lotions) and iontophoresis was investigated on the in vitro permeability of leuprolide acetate through porcine epidermis. Franz diffusion cells and Scepter iontophoretic power source were used for the percutaneous absorption studies. Anodal iontophoresis was performed at 0.2 mA/cm2 current density. Fatty acids used were palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3) acids. The passive and iontophoretic flux were significantly (p < 0.05) greater through fatty acids-treated porcine epidermis in comparison to the control (untreated epidermis) for leuprolide acetate. The passive and iontophoretic permeability of leuprolide acetate increased with increasing number of cis double bonds. Among the fatty acids tested, linolenic acid (C18:3) exhibited the maximum permeability of leuprolide acetate during passive (51.42 x 10(-4) cm/hr) and iontophoretic (318.98 x 10(-4) cm/hr) transport. The passive and iontophoretic flux of leuprolide acetate were significantly (p < 0.05) greater through the limonene and depilatory lotion treated epidermis in comparison to their respective control. In conclusion, iontophoresis in combination with chemical enhancers synergistically increased (p < 0.05) the in vitro permeability of leuprolide acetate through porcine epidermis.

Adjuvants, Pharmaceutic↗

PubMed2003

Electronically facilitated transdermal delivery of human parathyroid hormone (1-34).

Electronically facilitated transdermal delivery of human parathyroid hormone (1-34), hPTH (1-34), was investigated in vitro, using dermatomed porcine skin. The effect of iontophoretic current density, electroporative pulse voltages and also electroporation followed by iontophoresis was investigated on the in vitro percutaneous absorption of hPTH (1-34). Iontophoresis at 0.5 mA/cm2 current density significantly enhanced (P<0.05) the flux of hPTH (1-34) in comparison to passive flux. Electroporation pulses of 100, 200 and 300 V significantly increased (P<0.05) the flux of hPTH (1-34) in comparison with the passive as well as iontophoretic flux at 0.5 mA/cm2. The electroporative flux of hPTH (1-34) was found to vary linearly (R2 = 0.97) with the pulse amplitude. The principal barrier of the skin, stratum corneum, was found perturbed following the pulses as evident by light microscopy studies. The application of electroporation pulses followed by iontophoresis further increased the flux by several fold. The flux of hPTH (1-34) with the electroporation pulses of 100 and 300 V followed by iontophoresis at 0.2 mA/cm2 was 10- and 5-fold higher, respectively, in comparison to the flux with corresponding pulses alone. This shows the synergistic effect of iontophoresis in combination with electroporation on skin permeability of hPTH (1-34). The results indicate the possibility of designing controlled transdermal delivery systems for hPTH (1-34) using electroporation followed by iontophoresis.

Administration, Cutaneous↗

PubMed2003

Conformational stability of a model protein (bovine serum albumin) during primary emulsification process of PLGA microspheres synthesis.

The goal of this study was to investigate the conformational stability of a model protein, bovine serum albumin (BSA), during the primary emulsification process of poly(D,L-lactide-co-glycolide) (PLGA) microspheres preparation. Differential scanning calorimeter (DSC) was utilized to assess the conformational structure of BSA during primary emulsification in the presence and absence of PLGA. Three excipients [i.e. mannitol, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sodium dodecyl sulfate (SDS)] were investigated for their stabilizing effect on BSA during emulsification process. The DSC profile of intact BSA was best fitted by a non-2-state model with two peaks, which have midpoint temperatures (T(m1), 60.9 +/- 0.4 degrees C and T(m2), 66.4 +/- 1.0 degrees C), respectively, and a total calorimetric enthalpy Delta H(tot) of 599 +/- 42 kJ/mol. After emulsifying BSA aqueous solution with methylene chloride, an additional apparent peak at a higher temperature was observed. The T(m) of this peak was 77.4 +/- 0.8 degrees C. HP-beta-CD was able to suppress the occurrence of an additional peak, whereas mannitol failed. SDS increased the thermal stability of BSA dramatically. Furthermore, HP-beta-CD increased BSA recovery from 72 +/- 8% to 89 +/- 7% after extraction from w/o in the presence of PLGA. These results provided evidence that HP-beta-CD could be a promising excipient for conformational stability of BSA during synthesis of PLGA microspheres.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2003

In vivo percutaneous absorption, skin barrier perturbation, and irritation from JP-8 jet fuel components.

JP-8 jet fuel has been reported to cause systemic and dermal toxicities in animal models and humans. There is a great potential for human exposure to JP-8. In this study, we determined percutaneous absorption and dermal toxicity of three components of JP-8 (i.e., xylene, heptane, and hexadecane) in vivo in weanling pigs. In vivo percutaneous absorption results suggest a greater absorption of hexadecane (0.43%) than xylene (0.17%) or heptane (0.14%) of the applied dose after 30 min exposure. Transepidermal water loss (TEWL) provides a robust method for assessing damage to the stratum corneum. Heptane showed greater increase in TEWL than the other two chemicals. No significant (p < 0.05) increase in temperature was observed at the chemically treated site than the control site. Heptane showed greater TEWL values and erythema score than other two chemicals (xylene and hexadecane). We did not observe any skin reactions or edema from these chemicals. Erythema was completely resolved after 24 h of the patch removal in case of xylene and hexadecane.

Administration, Cutaneous↗

PubMed2003

Passive and iontophoretic transport enhancement of insulin through porcine epidermis by depilatories: permeability and fourier transform infrared spectroscopy studies.

The effect of thioglycolate-based depilatory lotions was studied on the in vitro passive and iontophoretic permeability of insulin through porcine epidermis and biophysical changes in the stratum corneum (SC) lipids and proteins. The porcine epidermis and Franz diffusion cells modified for iontophoresis were used for the in vitro transport studies. Cathodal iontophoresis was performed at 0.2 mA/cm2 current density. Resistance of the control- and depilatory-lotion-treated epidermis was determined according to Ohm's law. Biophysical changes were studied on porcine SC before (control) and after treatment with the depilatory lotions using Fourier transform infrared (FT-IR) spectroscopy. Asymmetric (approximately 2915 cm(-1)) and symmetric approximately 2848 cm(-1)) Carbon-Hydrogen (C-H) stretching absorbances were studied to estimate the extent of lipid extraction. Fourier self-deconvolution and second derivative procedures were applied to amide I band (1700-1600 cm(-1)) in order to estimate quantitatively the changes in the secondary structure of the SC protein. The passive permeability of insulin was significantly (P <.05) increased through depilatory-lotion-treated (ie, Better Off, Marzena, and Sally Hansen) epidermis in comparison to control. Iontophoresis significantly enhanced (P <.05) the permeability of insulin through depilatory-pretreated epidermis in comparison with the control epidermis. Further, we were able to achieve the desired flux of insulin (5.25 U/cm2/d) through Better Off-treated epidermis using 0.2 mA/cm2 current density and 100 U/mL donor concentration of insulin. The SC treated with depilatory lotions showed a decrease in peak areas of C-H stretching absorbances in comparison with untreated SC. Depilatory lotion treatment also decreased (P <.05) the epidermal resistance in comparison with the control epidermis. The decrease in the alpha-helix conformation and the increase in the random and turn structures were observed in the SC proteins due to depilatory lotion treatment. The changes in the secondary structure of proteins and lipid extraction from the SC are suggested as the cause of the decrease in the epidermal resistance and the increase in the passive and iontophoretic permeability of insulin through depilatory-pretreated epidermis in comparison with the control epidermis.

Animals↗