Rat Abdominal Skin Research Articles

Effective transcutaneous immunization against hepatitis B virus by a combined approach of hydrogel patch formulation and microneedle arrays

Transcutaneous immunization (TCI) has many advantages compared with needle-based administrations. But the conventional TCI shows poor permeation of antigens across the skin barrier. In this study, Functional MicroArray (FMA) system was used to poke the skin and increase the permeability, and the hydrogel patch formulation was used as the carrier for transdermal delivery of hepatitis B surface antigen (HBsAg) and cholera toxin B (CTB) as an adjuvant. In vitro permeation of antigen was studied using porcine ear skin and rat abdominal skin. The results showed that FMA system could significantly increase the permeation of HBsAg across skin compared with conventional TCI. HBsAg loaded hydrogel formulation exhibited better antigenic thermostability than the liquid formulation. In vivo immunization studies were performed in mice, and the serum IgG titer, IgG2a/IgG1 ratio were measured. The results showed that TCI with FMA induced more potent immune responses than the groups without FMA pretreatment. CTB adjuvanted TCI group could induce higher IgG titers compared with the group without CTB. Furthermore, TCI group can maintain a longer duration of stable IgG titers compared with the intramuscular injection (IM) group. In conclusion, the FMA/hydrogel system was proved to be a potential vaccination strategy against hepatitis B virus.

Effect of Permeation Enhancers on Transdermal Delivery of Venlafaxine Hydrochloride from Carbopol Gel

In this study, we investigated the effect of different permeation enhancers at different concentrations viz. oleic acid, olive oil and castor oil from transdermal gel for transdermal delivery of venlafaxine, a newer antidepressant. It is a first line drug in the treatment of depression and inhibits brain serotonin and norepinephrine neuronal reuptake. It is also used in the treatment of anxiety disorders. Transdermal delivery of venlafaxine hydrochloride may result in enhanced patient compliance by reducing the incidence of the undesirable GI problems associated with its multiple oral dosing. The differential scanning colorimetry study was used to investigate the drug-polymer interaction. The prepared gels were evaluated for several physico-chemical parameters such as drug content, spreadability, pH, viscosity and physical appearance to justify their suitability for topical use. The in vitro permeation studies were performed by using Franz diffusion cell and rat skin as a semi permeable membrane. This indicate that penetration enhancers in 5% v/w concentration enhance the permeation of venlafaxine hydrochloride but oleic acid show maximum permeation rate was 197 µg/cm2/hr as compared to olive oil (154.69µg/cm2/hr) and castor oil (175.8µg/cm2/hr). It is further optimized by increasing the concentration of permeation enhancer at levels as high as 10% v/w and 15% v/w. The result indicates that increase in the concentration of enhancer enhances the percutaneous permeation of venlafaxine. Oleic acid was found to be superior to olive oil and castor oil implying the ability of oleic acid to increase the drug diffusion by SC lipid disruption and increase partition coefficient into SC. The permeation rate of venlafaxine hydrochloride with 15% v/w oleic acid was higher (rat abdominal skin flux = 8.507 µg/cm2/h) than with 15% v/w olive oil and castor oil. These studies show promising potential of transdermal patches of venlafaxine.

Development of solid lipid nanoparticles based controlled release system for topical delivery of terbinafine hydrochloride

The study describes the development and evaluation of solid lipid nanoparticles (SLNs) of terbinafine hydrochloride (TH) for sustained release and skin targeting. TH-loaded SLNs were prepared by solvent-injection technique and optimized using 33 full-factorial design. Effect of drug:lipid ratio, surfactant concentration and volume of organic solvent were studied on % entrapment efficiency (%EE) and particle size (PS). The optimum formulation based on desirability (0.945) exhibited %EE of 73.74% and PS of 300nm. Optimized SLNs were incorporated into Carbopol gel and evaluated for drug content, pH, in vitro release, ex vivo retention, in vivo pharmacodynamic and stability studies. Drug release from SLNs dispersion followed Korsmeyer–Peppas model, indicating Fickian drug release, while that from the gel followed Higuchi model. The ex vivo studies through rat abdominal skin indicated skin retention ability of SLNs as compared to commercial product. In vivo pharmacodynamic studies showed that the SLNs based gel reduced fungal burden of Candida albicans in rats as compared to commercial product in shorter duration of time. The SLNs dispersion and gel exhibited physicochemical stability under refrigeration upto 3months. It was concluded that SLNs incorporated Carbopol gel had skin targeting ability and may serve as a promising carrier in treatment of fungal skin infections.

Transdermal Delivery of Verapamil HCl: Effect of Penetration Agent on In Vitro Penetration through Rat Skin

Verapamil Hydrochloride is a calcium channel blocking anti-anginal agent. Extensive first pass metabolism, low bioavailability (~20%) and short biological half life (4.8 hrs) altogether makes it an ideal candidate for transdermal drug delivery. The objectives of this study were to develop matrix-type transdermal patches of verapamil hydrochloride (VPL) with combinations of hydroxypropyl methyl cellulose (HPMC) and hydroxy propyl cellulose (HPC) as matrix polymers and to investigate the influence of oleic acid (OA) on in vitro permeation of VPL through rat skin. The permeation studies were performed using Franz-type diffusion cells and full-thickness excised abdominal rat skin. The effect of the polymers on the drug release, percentage moisture loss, percentage moisture absorption, folding endurance, and thickness, were investigated.. In vitro release studies showed zero-order release of the drug from all the patches, and the mechanism of release was diffusion mediated. Data was analysed using different release kinetic models. In vitro release profiles showed that from optimized combination the release of the drug was sustained and it extended over a period of 24 hr VPM 006 emerged as the most satisfactory formulation as far as its technological properties were concerned.

The rare sugar D-allose has a reducing effect against ischemia-reperfusion injury on the rat abdominal skin island flap model

BackgroundRecently, one of the rare sugars, D-allose, has received attention from many researchers because of its availability for mass production and its various physiological functions. Among these, an antioxidative effect has been strongly suggested. In this study, we investigated whether this effect is also applicable to the field of skin surgery. MethodsIn ischemia-reperfusion injury model using the rat abdominal skin island flap (male Wistar rats, n = 110), D-allose was injected intravenously 15 min before 8-h ischemia. The survival area (%) was measured by digital photographic assessment 1 wk after surgery, and multiple comparisons (Fisher's protected least significant difference) were carried out. Histopathological examination (neutrophilic infiltration into dermis in hematoxylin and eosin stain) and immunostaining (of ectodermal dysplasia-1 (ED1)-positive cells/flap) were assessed. Myeloperoxidase (MPO) activity in the skin flap (sampling at the time of 8 h after reperfusion) was measured spectrophotometrically, and Student t-test was performed. ResultsD-allose extended the survival of the remaining flaps, and a dose greater than 30 mg (0.1 mg/g) was necessary to be effective. The flap survival rates in the 30, 60, and 150 mg groups were significantly higher than that in the control (saline) group: 75.87 ± 5.90, 79.27 ± 7.81, and 77.87 ± 6.20 versus 50.53 ± 9.66, respectively (P < 0.05). ED1-positive cells/flap in 60 mg of D-allose and control (saline) were 78 ± 25.7 versus 124 ± 15.8, respectively (P = 0.08). The MPO activity in the D-allose 60 mg group was 0.40 ± 0.04, and that in the control (saline) was 0.72 ± 0.12. D-allose significantly reduced the skin tissue MPO activity (P < 0.05) compared with that in the control (saline) group. ConclusionsWe proved that D-allose has a reducing effect against ischemia-reperfusion injury on the skin island flap model, and the mechanism is related to inhibiting the activity of neutrophils in the skin tissues. Compared with chemo-synthetic materials, rare sugars are safer for our bodies as well as the environment; therefore, this rare sugar project is expected to lead to the development of a safer antioxidant for skin flap surgery.

Minimally Invasive Transdermal Delivery of Iron–Dextran

Iron deficiency is one of the most prevalent and serious health issues among people all over the world. Iron-dextran (ID) colloidal solution is one among the very few US Food and Drug Administration (FDA)-approved iron sources for parenteral administration of iron. Parenteral route does not allow frequent administration because of its invasiveness and other associated complications. The main aim of this project was to investigate the plausibility of transdermal delivery of ID facilitated by microneedles, as an alternative to parenteral iron therapy. In vitro permeation studies were carried out using freshly excised hairless rat abdominal skin in a Franz diffusion apparatus. Iron repletion studies were carried out in hairless anemic rat model. The anemic rats were divided into intact skin (control), microneedle pretreated, and intraperitoneal (i.p.) groups depending on the mode of delivery of iron. The hematological parameters were measured intermittently during treatment. There was no improvement in the hematological parameters in case of control group, whereas, in case of microneedle pretreated and i.p. group, there was significant improvement within 2-3 weeks. The results suggest that microneedle-mediated delivery of ID could be developed as a potential treatment method for iron-deficiency anemia.

Study on in vitro/in vivo correlation of extracts from Ligusticum chuanxiong after transdermal administration

To study the transdermal permeation and in vivo pharmacokinetics of effective constituent ferulic acid from Ligusticum chuanxiong, in order to establish the in vitro/in vivo correlation in transdermal permeation. Franz diffusion cell was adopted in the in vitro transdermal permeation, with CD-1 nude rat abdominal skin as the permeation medium. Linear probes were implanted in CD-1 nude rats. With PBS as perfusate, microdialysis was employed to study the pharmacokinetics. Ferulic acid concentrations in the receptor solution and dialysate were assessed by high performance liquid chromatography (HPLC). The study on correlation between in vitro and in vivo data was conducted by deconvolution methods. The transdermal permeation rate of ferulic acid from Ligusticum chuanxiong was (0.094 4 +/- 0.049 4) microg x cm2 x min, with Cmax of ferulic acid being 808.91 microg x L(-1), and Tmax being 183 min after dermal administration. The in vitro/in vivo correlation was 93.61. Ferulic acid in extracts from L. chuanxiong can quickly penetrate skins. By using the in vitro/in vivo correlation in transdermal permeation, simple in vitro transdermal permeation method can be adopted to study the changes in its pharmacokinetics.

Design and Evaluation of Miconazole Nitrate loaded Nanostructured Lipid Carriers (NLC) for improving the Antifungal therapy

The aim of this study was to prepare and evaluate gels incorporating nanostructured lipid carriers (NLC) of Miconazole nitrate (MN) for systemic delivery of the active after topical application. MN has been used as model drugs to be incorporated into nanostructured lipid carriers, once they are very well established as antimycotics for the treatment of topical fungal infections. NLC designed for topical administration of MN, were prepared by the hot high pressure homogenization technique. This MN-NLC was characterized for particle size, entrapment efficiency, and SEM. The lipid nanoparticles were incorporated in gels for convenient topical application and were evaluated forfor particle size, Rheological analysis Texture analysis , In vitro drug release studies and Ex Vitro skin permeation Studies. The preparation of aqueous NLC dispersions with a mean particle size lower than 300 nm has been obtained with uniform size distribution (PI < 0.350). The prepared semi-solid systems showed mean particle size remained lower than 250 nm and PI remained lower than 0.500 after 3 months of storage. An initial rapid release was observed in the case of Marketed gel, whereas MN- NLC Gel depicted a slow initial release with a lag time of 0.5 h and 1 h, respectively. High amount of MN release was facilitated through abdominal skin of rats from marketed gel than MN-NLC Gel. Research work could be concluded as successful development of MN-loaded NLC-bearing hydrogel to increase the encapsulation efficiency of colloidal lipid carriers with advantage of improved performance in terms of stability and provides a sustaining MN topical effect as well as faster relief from fungal infection.

Design and development of ethosomal transdermal drug delivery system of valsartan with preclinical assessment in Wistar albino rats

Valsartan (VLT) is a highly selective and orally active antihypertensive drug. However, its oral administration is associated with drawbacks like low bioavailability. The objective of this study was to design and develop a transdermal delivery system for VLT using ethosomal carriers to investigate their enhanced transdermal delivery potential. VLT ethosomes were prepared by cold method. VLT ethosomes were characterized by scanning electron microscopy. The prepared ethanolic liposomes were characterized to be spherical having low polydispersity of nano-size range with good entrapment efficiency. ETC5 ethosomal suspension with 4% of phospholipon 90H and 40% of ethanol was found to have highest entrapment efficiency, i.e. 80.230 ± 0.8748%. The permeation study of ethosomes was evaluated by ex vivo diffusion study through rat abdominal skin using Franz’s diffusion cells and ETC5 ethosomal suspension was found to have highest permeation with flux of 92.819 ± 1.539 µg/cm2/h, when compared to the permeation profiles of drug solutions either in water or in a water–ethanol mixture. Transdermal application of ethosomal VLT on Wistar rats showed better and prolonged antihypertensive activity in comparison to orally administered VLT suspension by virtue of transdermal permeation through Wistar rat skin. Histopathological study of skin applied with ETC5 showed intercellular permeation across skin by dissolving intercellular lipids in epidermis without causing any rigorous changes in the skin cellular structure. In conclusion, ethosomes enabled the transdermal permeation of VLT, which amply proves its superiority over oral administration for antihypertensive treatment.

Penetration effect of Ostrich Oil as a Promising Vehicle on Transdermal Delivery of Sinomenine

The present study investigated the feasibility of ostrich oil utilizing as a promising vehicle for improved skin permeation of sinomenine with reference to vaseline matrix containing different content of chemical enhancers. The fatty acid composition of ostrich oil was analyzed by GC-MS. Penetration enhancing potential of ostrich oil on permeation of sinomenine across rat abdominal skin in vitro was studied using an automatic diffusion cell apparatus. The content of sinomenine percutaneous absorbed was determined by HPLC. Various parameters viz. steady-state skin flux (J(ss)), permeability coefficient (kP), cumulative amount of sinomenine (Q) and enhancement ratios (ER) were calculated from the permeation data. Fick's law of diffusion and Scheuplein kinetic were used to evaluate the transdermal absorbent enhancement of ostrich oil to sinomenine. Ostrich oil showed significant penetration effect on sinomenine compared with vaseline matrix containing different content of chemical enhancers, the density sequence as follow: 2% Azone > ostrich oil > 1% Azone plus 1% propylene glycol > 1% Azone > 3% Azone > 1% propylene glycol. The percutaneous endosmic rate constant (J(ss)) and permeability coefficient (k(P)) of sinomenine in ostrich oil through rat skin were 10.01 μg/cm²/h and 0.087, respectively. Ostrich oil produced stronger enhancement (ER = 24.31) with greater cumulative amount of drug permeated (255.53 μg/cm²) up to 24 h and caused no skin irritation. The drug release of sinomenine was coincided with Fick's equation. In summary, ostrich oil containing fatty acids is proposed as a promising adjuvant for use in cosmetics and pharmaceuticals for improved permeation of drug.

Synergistic Effect and Mechanism of Cineole and Terpineol on In-vitro Transdermal Delivery of Huperzine A from Microemulsions.

The aim of the present study was to investigate the influence and the mechanisms of cineole and terpineol on the in-vitro transdermal delivery of huperzine A from microemulsions, and their potential synergistic effect on the permeation enhancement. The transdermal delivery of huperzine A from microemulsions with different concentrations of cineole and terpineol through the rat abdominal skin was determined by Franz-type diffusion cells. The partition coefficient of huperzine A between the full thickness skin and microemulsion was determined. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was carried out to analyze the effects of cineole and terpineol on the biophysical properties of the stratum corneum (SC) and the mechanisms of permeation enhancement. These results indicated that cineole and terpineol could synergistically increase the transdermal delivery of huperzine A from microemulsions through increasing the partition and diffusion coefficients of huperzine A. ATR-FTIR studies further validated the synergistic effect and revealed that the enhancing mechanisms were due to increasing the disorderliness and fluidity of SC lipid alkyl chains, disrupting the structure of keratin in SC, and extracting SC lipids. In conclusion, cineole and terpineol, acting synergistically to enhance the transdermal delivery of huperzine A from microemulsions, might provide an alternative permeation enhancer combination for the transdermal delivery of huperzine A.

Recovery Rate of Rat Skin Micropores Made by Dissolving Microneedles

The physiological recovery rate of skin was studied using dissolving microneedles (DMs) made of chondroitin sulfate. Chips of two kinds were prepared having conical DMs as an array: (1) a 300 DM array chip having a sharp tip with mean diameter of 4.7 ± 0.2 μm, and a (2) 225 DM array chip having a less-sharp tip with mean diameter of 15.3 ± 0.3 μm. Under anesthesia, DMs were inserted into abdominal rat skin from which the hair had been removed. The kinetics of skin healing was studied by pathological and biochemical methods. At 5, 30, 45 min, and at 1 and 3 h after the removal of the DM array chip, the skin was stained with 0.25 % Evans blue solution before pathologic observations were performed. The skin physiology recovered to its normal state at 45 min with both DMs. Biochemical study was also performed by measuring the leaked amount of lactose dehydrogenase (LDH) activity. The maximum leaks, 199.3 ± 13.0 % (225 DMs) and 153.4 ± 23.2 % (300 DMs) appeared at 5 min. In both DMs, the micropores formed on the skin healed within 60 min. Pathological and biochemical examinations revealed that skin recovered to the pre-treatment level within 1 h. The effect of the adhesion length of the chips onto the skin on the skin’s recovery rate was studied by attaching two DMs to the rat skin for 6 h. Maximal leaks were detected at 5 min after administration, i.e., 157.8 ± 10.1 % for 300 DMs and 215.6 ± 5.4 % for 225 DMs. However, the leakage returned to the pretreatment level at 60 min. Therefore, DMs were found to be a low-invasive TDDS for drugs.

Method to Increase the Systemically Delivered Amount of Drug from Dissolving Microneedles

To increase the absorbed amount of a drug from dissolving microneedles (DMs), three DM array chips were prepared in which (1) the drug was localized at the acral portion of DMs, (2) the drug was loaded in each whole DM, and (3) the drug was loaded in DMs and the chip. Fluorescein free form (FL) and its sodium salt (FLNa) were used as model drugs. The DM array chip had 15-mm diameter with 225 DMs, each 500-µm long with a 300-µm diameter base. The respective FLNa contents in the three chips were (1) 0.18±0.03, (2) 0.64±0.07, and (3) 10.95±1.07 mg. The FL contents were (1) 0.20±0.01, (2) 0.68±0.03 and (3) 12.47±1.01 mg. The in vitro release of fluorescein from FLNa DMs was faster than that from FL DMs. In vitro permeability experiments showed that (3) produced the greatest increase in the permeability of fluorescein through rat skin, especially in FLNa loaded DMs. In vivo rat absorption study by application of DM array chips to the rat abdominal skin for 6 h demonstrated that the systemically absorbed amount of fluorescein increased from 0.18±0.02 mg, 0.53±0.19 mg, to 5.38±1.99 mg from systems (1) and (2)-(3). By decreasing the application time of DMs to the rat skin, the absorbed amount of fluorescein decreased along with the application time. The physiological state of the skin recovered within 30 min after chip removal. Using a type (3) DM array chip, more than 1.0 mg of water-soluble drug can be delivered to the systemic circulation.

Investigation of the ex vivo and in vivo iontophoretic delivery of aceclofenac from topical gels in Albino rats

Introduction:Iontophoresis was used to enhance the delivery of aceclofenac (ACF) from topical gels formulated with various polymers for the purpose of relieving pain and inflammation.Materials and MethodsGels were formulated from hydroxypropyl methyl cellulose (HPMC), carbopol 934P, and sodium carboxymethyl cellulose (NaCMC). The formulations were evaluated for cathodal iontophoretic delivery of ACF through excised rat abdominal skin at three levels of current density of 0.5, 0.6 and 0.7 mA/cm2. The in vivo effectiveness of the drug delivered passively as well as under the influence of iontophoresis at pH 7.4 at a current density of 0.5 mA/cm2 was also investigated using male Albino rats with carrageenan induced paw edema.Results and Discussion:In the ex vivo studies, though it was clear that iontophoresis significantly increased drug permeation through the excised skin from all formulations; the percentage drug permeated from HPMC gels was superior to that from carbopol 934P or NaCMC gels but increased with an increase in the current density only for the former. The steady state flux, permeability coefficient, enhancement factor were significantly greater from HPMC gels than from the gels of the ionic polymers due to the interference of competitive ions. With iontophoresis, the carrageenan induced paw edema was significantly reduced by 61.53% (P < 0.01) for HPMC gels as compared to the control although passive permeation without iontophoresis showed a 54.6% reduction (P < 0.05) at the end of 4 h.Conclusion:The results of the study indicate that ACF could be administered topically by using iontophoresis from a suitably formulated gel for effective control of pain and inflammation.

Usefulness of Basic Fibroblast Growth Factor (bFGF) Loaded Dissolving Microneedles for Local Therapy of Skin Wounds

Purpose: The usefulness of dissolving microneedles (DMs) for local skin therapy by basic fibroblast growth factor (bFGF) was studied in rats. Methods: We prepared four kinds of bFGF-loaded DMs, approximately 500 μm length and 300 μm diameter at the bottom. Long-term stability and dissolution studies were performed by HPLC method. Pharmacokinetic and pharmacological evaluations were performed after administration of bFGF loaded DMs to rats. Results: The bFGF contents were 2.15 ± 0.07, 1.07 ± 0.04, 0.56 ± 0.07 and 0.12 ± 0.03 μg. The 100.2 ± 3.4%, 100.2 ± 3.3%, 99.3 ± 1.4% and 100.4 ± 3.0% of bFGF were recovered after 1, 3 and 6 months and 1 year incubation at 40°C. The bFGF was released from DMs within 5 min. In a pharmacokinetic study using 2.0 and 1.0 μg bFGF-loaded DMs, no systemic exposure of bFGF was detected. The initial bFGF concentrations in the rat skin tissue after administration of bFGF-loaded DMs to the hair-removed rat abdominal skin were 510.2 ± 20.1 ng/g wet weight for 2 μg bFGF DMs and 264.2 ± 56.5 ng/g wet weight for 1 μg DMs, declining slowly thereafter to 226.3 ± 33.5 and 105.1 ± 27.4 ng/g wet weight at 6 hr after administration. Good dose-dependency was observed. Pharmacological evaluation of bFGF-loaded DMs of 2.0, 1.0, 0.5, and 0.1 μg, in the wound healing rat model, all used DMs, but 0.1 μg DMs, showed good healing effects. Considered collectively, these results suggest the usefulness of bFGF-loaded DMs for local therapy of skin wound disease.

Effect of chemical enhancers in transdermal permeation of alfuzosin hydrochloride.

The objective of the present study is to explore the efficient chemical penetration enhancer among the various enhancers available in overcoming the stratum corneum barrier in transdermal delivery of Alfuzosin hydrochloride (AH). The different enhancers were incorporated in 2% Carbopol gel which was selected as a control and evaluated by in vitro diffusion studies through dialysis membrane and permeation through the rat abdominal skin using Keshary-Chien diffusion cells. All the enhancers increased the release rate through the dialysis membrane when compared with control except oleic acid which decreased the release rate but showed maximum solubility of the drug. Among the various enhancers Transcutol 20% and tween-20 (2%) showed the highest cumulative amount (Q 24) of 702.28 ± 6.97 μg/cm2 and 702.74 ± 7.49 μg/cm2, respectively. A flux rate of 31.08 ± 0.21 μg/cm2/hr by Transcutol 20% and 30.38 ± 0.18 μg/cm2/hr by tween-20 (2%) was obtained. Transcutol 20% showed decreased lag time of 0.13 ± 0.05 hr. The lowest skin content of 342.33 ± 5.30 μg/gm was seen with oleic acid 2.5%. Maximum enhancement of flux by 3.94-fold was obtained with transcutol 20%. Primary skin irritation studies were performed with rabbit. Histopathological studies of transcutol 20% showed marked changes such as degeneration and infiltration of mononuclear cells in dermis indicating the effect of transcutol on the skin. Among the different enhancers transcutol is efficient in enhancing transdermal delivery of AH.

Transdermal microgels of gentamicin

Phospholipid-modified solid lipid microparticles (SLMs) of Phospholipon® 90G and 90H encapsulating the hydrophilic drug, gentamicin were produced and loaded into three polymeric hydrogels of Poloxamer 407 and polyacrylic acids (Carbopols® 971P and 974P). The SLMs were characterized by morphology and particle size, drug encapsulation efficiency, thermal properties, pH, and storage stability, whereas the microgels were evaluated for viscosity, spreadability, pH, drug content, and in vitro antimicrobial drug release against five microorganisms (Klebsiella spp., Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa). Our results generally showed Poloxamer 407 microgels of P90H and P90G as having the most desirable properties in terms of fast antibacterial activity on all tested microorganisms, in vitro diffusion-dependent permeation through rat abdominal skin, spreadability, pH, and viscosity, superior to polyacrylic acids microgels.

English

This study evaluates the ability of the terpenes incorporated in liposomes on the&nbsp;in vitro&nbsp;skin delivery of hydrophobic model drug, nimesulide (NE). To this purpose, so-called terpene liposomes (TPs), which are composed of phospholipid and three types of terpene, citral, limonene and cineole. The obtained formulations were characterized in terms of size distribution, zeta potential and morphology. The efficiency of TPs on skin delivery of NE was studied using&nbsp;in vitro&nbsp;Franz diffusion cells and abdominal rat skin in comparison with conventional liposomes and ethanolic solutions of NE. Results showed that all the used TPs had spherical structures with negative zeta potential, low polydispersity (PDI &lt; 0.2), nanometric size range (z-average no more than 150 nm). TPs improved the entrapment efficiency (EE%) and gave good physical stability.&nbsp;In vitro&nbsp;skin permeation data showed that TPs were able to give a significant improvement of NE permeation through the rat skin in comparison with conventional liposomes and drug solution. Moreover, the TPs prepared with limonene were also able to deliver a higher amount of NE than the other formulation, thus suggesting that NE delivery to the skin was strictly correlated to type of terpenes incorporated liposomes. &nbsp; Key words:&nbsp;Nimesulide, terpene liposomes,&nbsp;in vitro&nbsp;skin permeation.

Development, Characterization, and Evaluation of Celecoxib Microemulsion for Topical Delivery

In the present research, the potential of topical microemulsion delivery of poorly aqueous soluble drug, that is, Celecoxib, was investigated. Microemulsions are regarded as highly biocompatible topical carrier systems for the delivery of several anti-inflammatory, local anesthetics, anti-infective drugs. Microemulsion vehicles composed of various proportions of oleic acid, Lipoid E80, and Capryol 90/PEG 400 as oil phase, surfactant, and cosurfactant phase, respectively. A pseudo-ternary phase diagram was constructed at room temperature by titration method, and the oil-to-surfactant/co-surfactant volume ratios (O/SC) that exhibit the maximum solubilization of water were determined. Microemulsion formulations were physically characterized for globule size, thermal stability, centrifugation stress testing, specific gravity, pH, and in vitro permeation studies on rat abdominal skin. The permeation data showed that microemulsion formulation, ME-2, showed increased Celecoxib flux to several-fold over the control vehicle, that is, the self-prepared gel formulation. It was concluded from the above studies that microemulsions could be a promising dosage form to improve drug stability in topical formulations.

Transdermal Insulin Application System with Dissolving Microneedles

The aim of this report was to develop a dissolving microneedle (DM) application system, where 225-300 insulin-loaded DMs were formed on a chip. After the heat-sealed sheet is removed, the system covered with the press-through package layer is put on the skin. By pressing with the hand, insulin DMs were inserted into the skin. Factors affecting the penetration depth of DM were studied using applicator in vitro and in vivo experiments. The penetration depth was determined for rat and human skin. Two-layered DM array chips were prepared to obtain complete absorption of insulin and administered to the rat abdominal skin. Plasma glucose levels were measured for 6 h. By comparing the hypoglycemic effect with that obtained after subcutaneous injection, relative pharmacological availability (RPA) was determined. The penetration depth increased from 21 ± 3 μm to 63 ± 2 μm in proportion to application speed to isolated rat skin, at 0.8-2.2 m/s. Human skin showed similar results in the penetration depth. The in vivo penetration depth was dependent on the force (0.5-2.5 N) and duration (1-10 min), as the secondary application force. The penetration depth was 211 ± 3 μm with a duration of 3 min in the in vivo rat experiment. DM array chips having an insulin-loaded space of 181.2 ± 4.2 and 209 ± 3.9 μm were evaluated in the rat. RPA values of insulin from DMs were 98.1 ± 0.8% and 98.1 ± 3.1%, respectively. These results suggest the usefulness of the two-layered DM application system for the transdermal delivery of insulin.