Topical Skin Application Research Articles

Electrospun Resveratrol-Loaded Polyvinylpyrrolidone/Cyclodextrin Nanofibers and Their Biomedical Applications.

Resveratrol is a naturally occurring polyphenol compound which has been shown to possess antioxidant and anti-inflammatory properties. However, its pharmaceutical applications are limited by its poor water solubility. In this study, we used electrospinning technology to synthesize nanofibers of polyvinylpyrrolidone (PVP) and hydroxypropyl-β-cyclodextrin (HPBCD) loaded with resveratrol. We used X-ray diffractometry to analyze crystalline structure, Fourier transform infrared spectroscopy to determine intermolecular hydrogen bonding, antioxidant assays to measure antioxidant activity, and Franz diffusion cells to evaluate skin penetration. Our results showed that the aqueous solubility of resveratrol nanofibers was greatly improved (by more than 20,000-fold) compared to the pure compound. Analysis of physicochemical properties demonstrated that following nanofiber formation, resveratrol was converted from a crystalline to amorphous structure, and resveratrol formed new intermolecular bonds with PVP and HPBCD. Moreover, resveratrol nanofibers showed good antioxidant activity. In addition, the skin penetration ability of resveratrol in the nanofiber formulation was greater than that of pure resveratrol. Furthermore, resveratrol nanofibers suppressed particulate matter (PM)-induced expression of inflammatory proteins (COX-2 and MMP-9) in HaCaT keratinocytes. Therefore, resveratrol-loaded nanofibers can effectively improve the solubility and physicochemical properties of resveratrol, and may have potential applications as an antioxidant and anti-inflammatory formulation for topical skin application.

Myorelaxant Effect of Cannabis Cream Topical Skin Application in Patients With TMD

Myorelaxant Effect of Cannabis Cream Topical Skin Application in Patients With TMD

Nanoemulsion and Nanoliposome Based Strategies for Improving Anthocyanin Stability and Bioavailability.

Background: Anthocyanins, a flavonoid class of water-soluble pigments, are reported to possess several biological activities, including antioxidant, anti-inflammatory, and anti-cancer. However, anthocyanins are highly susceptible to degradation in high pH, light, heat, and oxygen during processing and storage. Conventional microencapsulation techniques fail to provide stability to anthocyanins under physiological environments mainly because of their large particle size as well as low zeta potential and encapsulation efficiency. Methods: Nanotechnology provides novel strategies for preparing nanoformulations to enhance the physicochemical stability of anthocyanins. Nanoemulsion and nanoliposome are the two most commonly used nanosystems in pharmaceutical and food-related fields. In this review, an overview of various nanoemulsion and nanoliposome systems reported recently for enhancing stability, bioavailability, and bioactivity of anthocyanins is presented. Results: Anthocyanin nanoemulsions with different oil, water, surfactant, and cosurfactant ratios were prepared from extracts of mangosteen peel, purple sweet potato, cranberry, red cabbage, blueberry, jaboticaba peel, and acai berry and evaluated for their antioxidant activity, enhancement of physicochemical stability, topical skin application, and urinary tract infection. Likewise, unilamellar and multilamellar nanoliposomes were prepared using different types and levels of lecithin without or with cholesterol from anthocyanin standards and extracts of Hibiscus sabdariffa, mulberry, elderberry, black carrot, and pistachio green hull for the evaluation of physicochemical and oxidative stability, in vitro bioaccessibility, and melanogenic activity, as well as protective effects against diabetes mellitus and cataract. Conclusion: This review provides an insight into the current nanotechnology updates on enhancement of anthocyanin stability and biological activity.

Pharmacokinetics and Tissue Distribution of Pilocarpine After Application to Eyelid Skin of Rats

Extending the delivery of drugs into the eyes while reducing systemic bioavailability is of utmost importance in the management of chronic ocular diseases. Topical application onto the lower eyelid skin, as an alternative to eye drops, is seen to be a valuable strategy in the treatment of chronic eye diseases. To elucidate the critical value of delivering drugs in solution onto the eyeball through the eyelid skin, pharmacokinetic studies of pilocarpine were conducted, and the results were verified using a direct pharmacodynamic study in rats. The mean residence time of pilocarpine after topical eyelid application to the eyelid skin, conjunctiva, eyeball, and plasma were 14.9, 8.50, 6.29, and 8.11 h, respectively. Conjunctiva and eyeball concentrations of pilocarpine at 8 h were 80-fold and 8-fold higher after topical eyelid application, respectively, than those for eye drops. Pupillary constriction was sustained over 8 h after topical eyelid application. Topical eyelid skin application exhibited a localized drug absorption and specific drug accumulation in the ocular tissues. Hence, it is rational to prepare topical formulations directed onto the eyelid skin, which is suitable for drugs required for long-term treatment.

The Topical Skin Application of Purple Corn Extract (Zea Mays) Inhibited the Increase in MMP-1 Levels and Decreased Collagen in Wistar Rats (Rattus Norvegicus) Exposed to UV-B Rays

Formation of free radicals is an important mechanism causing skin aging. Free radicals are highly reactive molecules with unpaired electrons which can directly disrupt various structures of cell membrane, lipids, proteins, and DNA. Antioxidant is a substance which can give protection from endogenous and exogenous oxidative pressure caused by free radicals. Purple corn contains phenolic acid, vitamin C, and anthocyanin. Anthocyanin is the main contained substance in purple corn and acts as antioxidant and able to inhibit aging process on skin surface of mice exposed with UV-B ray. This research aims to prove the effectivity of administration of purple corn extract cream on inhibiting the elevation of MMP-1 level and the decrease of collagen amount on Wistar mice (Rattus norvegicus) exposed with UV-B. This research is animal experiment with post test only control group design. As many as 36 mice were divided into 2 groups containing 18 mice each, control group with appliance of placebo cream and intervention group applied with 50% purple corn extract cream. All groups were exposed with UV-B with dose of 840 mJ/cm² for 4 weeks, and biopsy was taken to examine the level of MMP-1 and collagen amount on dermis. The results of Shapiro-Wilk and Levene’s test showed that the data distribution between the two groups was normally distributed with homogenous variance and p ≥ 0.05. Comparative analysis with t-independent test showed that there is a significant difference between both groups, either on the mean level of MMP-1 or the collagen amount on both groups with p < 0.05. The mean collagen amount and mean MMP-1 level of intervention 2 are 71.7% and 1.9 mg/ml, respectively. Intervention-1 group shows the mean amount of collagen and MMP-1 level are 65.54 % and 3.22 mg/ml, respectively. The conclusion of this research is the administration of 50% purple corn extract cream inhibits the increase of MMP-1 level and the decrease of the amount of dermal collagen on mice’s skin exposed with UV-B.

Formulation characterization and in vitro drug release of hydrogel-thickened nanoemulsions for topical delivery of 8-methoxypsoralen

Psoralens are lipophilic molecules used to treat skin diseases such as vitiligo and psoriasis, among them, 8-Methoxypsoralen (8-MOP) is the most used to topical skin application. Topical treatment with psoralens can be limited due to insufficient drug penetration into the skin layers. Nanoemulsions have attracted much attention due to their as dermal delivery systems for lipophilic drugs such as 8-MOP. However, nanoemulsions feature low viscosity, which might be unsuitable for topical application. In this work, we produced hydrogel-thickened nanoemulsions using chitosan with different molecular weight as thickening polymer to overcome the low viscosity attributed to nanoemulsions. The aim of this study is to characterize oil-in-water (o/w) nanoemulsions and hydrogel-thickened nanoemulsions based on two different essential oils to in vitro controlled release of 8-MOP. In a previous work, we have reported production, stability and in vitro transdermal release of such formulations. Here, 8-MOP loaded nanoemulsions and hydrogel-thickened nanoemulsions were characterized regarding their morphology, rheological behavior, and in vitro drug release kinetics. Hydrogel-based systems presented a gel-like rheological behavior, being classified as weak gels. 8-MOP in vitro release from hydrogels-based formulations using clove essential oil showed strong dependency chitosan molecular weight. On the other hand, hydrogel-thickened nanoemulsions using sweet fennel oil as inner phase, showed an unexpected pH-dependent behavior not fully understood at the moment. These results need further investigation, nevertheless hydrogel-thickened nanoemulsions revealed to be interesting and complex dermal delivery systems for poorly soluble drugs.

Transdermal anti-nuclear kappaB siRNA therapy for atopic dermatitis using a combination of two kinds of functional oligopeptide

Nucleic acid-based targeting of nuclear factor kappaB (NF-κB) is gaining attention as a treatment option for skin diseases like atopic dermatitis (AD). Transdermal administration improves patient quality of life because of non-invasive; however, siRNA delivery into the skin can be challenging owing to the barrier of tight junctions in the granular layer. Therefore, we aimed to develop a delivery system of siRNA for topical skin application using functional peptides. We previously reported that combined treatment with a cytoplasm-responsive stearylated-arginine-rich peptide (STR-CH2R4H2C) and a tight junction opening peptide (AT1002) showed high siRNA permeability in the skin of AD-induced and normal mice. Here, we used murine macrophage RAW264.7 cells to examine siRNA permeation and the therapeutic effect of anti-NF-κB (RelA) siRNA (siRelA) complexed with STR-CH2R4H2C and AT1002 for AD-induced mice. We showed that significantly higher siRNA cellular uptake occurs after this treatment as well as decreased TNF-α and IL-6 expression. Additionally, we showed that effective siRNA transdermal delivery occurs with the suppression of the tight junction protein ZO-1. Moreover, topical skin application of siRelA with STR-CH2R4H2C and AT1002 improved AD-like symptoms in model mice. Thus, the combined treatment of STR-CH2R4H2C and AT1002 could serve as an effective transdermal siRNA therapeutic system for AD.

Anti-Inflammatory and Skin Barrier Repair Effects of Topical Application of Some Plant Oils.

Plant oils have been utilized for a variety of purposes throughout history, with their integration into foods, cosmetics, and pharmaceutical products. They are now being increasingly recognized for their effects on both skin diseases and the restoration of cutaneous homeostasis. This article briefly reviews the available data on biological influences of topical skin applications of some plant oils (olive oil, olive pomace oil, sunflower seed oil, coconut oil, safflower seed oil, argan oil, soybean oil, peanut oil, sesame oil, avocado oil, borage oil, jojoba oil, oat oil, pomegranate seed oil, almond oil, bitter apricot oil, rose hip oil, German chamomile oil, and shea butter). Thus, it focuses on the therapeutic benefits of these plant oils according to their anti-inflammatory and antioxidant effects on the skin, promotion of wound healing and repair of skin barrier.

Melatonin reverses the enhanced oxidative damage to membrane lipids and improves skin biophysical characteristics in former-smokers – A study in postmenopausal women

Protective antioxidative effects of melatonin have been repeatedly documented in experimental and clinical studies. One of the most spectacular exogenous prooxidative agents is cigarette smoking. The aim of the study was to evaluate the level of oxidative damage to membrane lipids (lipid peroxidation; LPO) in blood serum, and in epidermis exfoliated during microdermabrasion collected from former-smokers who were treated with melatonin. The study was performed in postmenopausal women. Ninety (90) female volunteers, aged 46-67 years, were enrolled. Two major groups, i.e. never-smokers (n=44) and former-smokers (n=46), were divided into: Control, melatonin topical skin application, Restructurer (containing antioxidants) topical skin application, and melatonin oral treatment. Microdermabrasion was performed at point '0', after 2 weeks, and after 4 weeks of treatment. The following parameters were measured: LPO in blood serum, LPO in epidermis exfoliated during microdermabrasion, and skin biophysical characteristics, such as sebum, moisture, elasticity, and pigmentation. Malondialdehyde+4-hydroxyalkenals level (LPO index) was measured spectrophotometrically. Melatonin oral treatment significantly reversed the increased serum LPO level in former-smokers already after 2 weeks of treatment. In a univariate regression model, LPO blood level constituted the only independent factor negatively associated with melatonin oral treatment. After 4 weeks of treatment, melatonin given orally increased skin sebum, moisture and elasticity levels, and melatonin applied topically increased sebum level. Exogenous melatonin reverses the enhanced oxidative damage to membrane lipids and improves skin biophysical characteristics in former-smokers.

Climbazole boosts activity of retinoids in skin.

To explore whether climbazole enhances retinoid-associated biological activities in vitro and in vivo. Primary human dermal fibroblasts (HDFs) were treated from six to 48 h with either retinoids (retinol, retinyl propionate, retinyl palmitate) alone or in combination with climbazole, and then assessed for cellular retinoic acid-binding protein 2 (CRABP2) mRNA expression by RT-qPCR. Next, skin equivalent (SE) cultures were topically treated with retinol or retinyl propionate, with or without climbazole, and then measured for biological changes in retinoid biomarkers. Lastly, an IRB-approved clinical study was conducted on the outer forearm of 16 subjects to ascertain the effects of low (0.02%) or high (0.1%) levels of retinol, retinyl propionate (0.5%), climbazole (0.5%) or a combination of retinol (0.02%)/climbazole (0.5%). Indicators of retinoid activities were measured after 3 weeks. Treatment of HDFs with retinol or retinyl propionate was unaffected by climbazole but alone, resulted in a significantly (P < 0.01) higher sustained CRABP2 mRNA expression than those treated with retinyl palmitate or vehicle control. In SEs, climbazole combined with either retinol or retinyl propionate boosted retinoid related activity greater than the retinoid only, reflected by a dose-response, downregulation of loricrin (LOR) and induction of keratin 4 (KRT4) proteins. In vivo, retinol (0.1%) and retinyl propionate (0.5%) significantly increased most evaluated biomarkers, as expected. Low-dose retinol or climbazole alone did not increase these biomarkers; however, in combination, significant (P < 0.05) increases in retinoid and ageing biomarkers were detected. Climbazole boosted retinoid activity both in the SE model, after a combined topic treatment with either retinol or retinyl propionate, and in vivo, in combination with a low level of retinol. Based upon the evidence presented here, we suggest that the topical skin application of climbazole in combination with retinoids could deliver skin ageing benefits more than a less robust retinoid alone.

ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phospholipase C γ1 and protein kinase C pathways.

The vitally important skin barrier is formed by extensive cross-linking activity of transglutaminases (TGs) during terminal epidermal differentiation. We have previously shown that epidermal deficiency of a disintegrin and metalloproteinase 17 (ADAM17), the principal EGFR ligand sheddase, results in postnatal skin barrier defects in mice due to impeded TG activity. However, the mechanism by which ADAM17/EGFR signalling maintains TG activity during epidermal differentiation remains elusive. Here we demonstrate that ADAM17-dependent EGFR signalling promotes TG activity in keratinocytes committed to terminal differentiation by direct induction of TG1 expression. Restored TG1 expression of EGF-stimulated differentiated Adam17−/− keratinocytes was strongly repressed by inhibitors for PLCγ1 or protein kinase C (PKC) pathways, while treatment with the PKC stimulator 12-O-tetradecanoylphorbol-13-acetate restored TG activity in the epidermis of keratinocyte-specific Adam17−/− (AD17ΔKC) mice. Further investigations emphasized the expression of PKCη, a mediator of TGM1 transcription, to be sensitive to EGFR activation. In agreement, topical skin application of cholesterol sulfate, an activator of PKCη, significantly improved TG activity in epidermis of AD17ΔKC mice. Our results suggest ADAM17/EGFR-driven PLCγ1 and PKC pathways as important promoters of TG1 expression during terminal keratinocyte differentiation. These findings may help to identify new therapeutic targets for inflammatory skin diseases related to epidermal barrier defects.

Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide.

As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times) back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM)-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery.

Evaluation of Effects of Topical Estradiol Benzoate Application on Cutaneous Wound Healing in Ovariectomized Female Mice.

Estrogen promotes cutaneous wound healing in ovariectomized (OVX) female mice. However, the effects of topical estrogen application on wounds remain unclear. Therefore, the aim of this study was to compare the effects of topical estrogen application on wounds with standard treatment methods. Eight-week-old C57BL/6J female mice underwent OVX and received two full-thickness wounds four weeks later. Mice were divided into three groups: topical estradiol benzoate (EB) (0.75 μg/g/day) wound treatment, subcutaneous estradiol (E2) pellets (0.05 mg, 21 days), and topical E2 (0.01 g/day) skin application. Wound healing was observed until day 14. Wound area ratios were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet group on days 1–14 (p < 0.05) and topical E2 skin application group on days 1–9 (p < 0.05). Neutrophil and macrophage numbers were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 skin application groups on day 7 (p < 0.05). Moreover, the number of new blood vessels and ratio of myofibroblasts were significantly larger in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 application skin groups on day 7 (p < 0.05). These results demonstrate that the application of estrogen to wounds reduced inflammatory responses and promoted angiogenesis and wound contraction more than the two other standard treatment methods.

Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis.

The small interfering RNA (siRNA) is suggested to offer a novel means of treating atopic dermatitis (AD) because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB) subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC), which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA.

Susceptibility in vitro of canine methicillin-resistant and -susceptible staphylococcal isolates to fusidic acid, chlorhexidine and miconazole: opportunities for topical therapy of canine superficial pyoderma.

ObjectivesIncreasing multidrug resistance amongst canine pathogenic staphylococci has renewed interest in topical antibacterial therapy for skin infections in the context of responsible veterinary prescribing. We therefore determined the activity in vitro of three clinically relevant topical agents and synergism between two of them against Staphylococcus pseudintermedius and Staphylococcus aureus.MethodsThe MICs of fusidic acid (n = 199), chlorhexidine (n = 198), miconazole (n = 198) and a 1:1 combination of miconazole/chlorhexidine (n = 198) were determined for canine isolates [50 MRSA and 49 methicillin-resistant S. pseudintermedius (MRSP), 50 MSSA and 50 methicillin-susceptible S. pseudintermedius (MSSP)] collected from the UK and Germany using an agar dilution method (CLSI VET01-A4). Fractional inhibitory concentration (FIC) indices were calculated to assess the interaction of miconazole with chlorhexidine.ResultsMICs of each drug/combination were significantly (P < 0.0005) higher for S. aureus when compared with S. pseudintermedius. Most strains (n = 172) had an MIC of fusidic acid of ≤0.03 mg/L (MIC ≥64 mg/L, n = 5 MRSA). All strains had MICs of chlorhexidine of 0.5–4 mg/L, except for one MRSA (MIC = 8 mg/L). All but four strains had MICs of miconazole of 1–4 mg/L (MIC = 16 mg/L, n = 3; MIC = 256 mg/L, n = 1). Miconazole/chlorhexidine (1:1 ratio) had a synergistic effect against 49/50 MRSA, 31/50 MSSA, 12/49 MRSP and 23/49 MSSP.ConclusionsSince the majority of these staphylococci, including methicillin-resistant isolates, had MICs that should be readily exceeded by topical skin application of these agents, their therapeutic efficacy for canine superficial pyoderma should be assessed. The synergistic interaction shown in vitro supports further clinical evaluation of miconazole/chlorhexidine combination therapy for staphylococcal infection.

Smart hydrogel-functionalized textile system with moisture management property for skin application

In this study, a functional textile-based material for topical skin application was fabricated by coating a thermoresponsive hydrogel onto one side of absorbent nonwoven fabric. The thermoresponsive hydrogel was synthesized easily through coupling of poly (ethylene glycol) (PEG) and poly (ϵ-caprolactone) (PCL) with hexamethylene diisocyanate (HMDI) as a chemical linker. The chemical structure of the as-prepared triblock copolymer hydrogel was unraveled by FTIR and 1H NMR analysis. The hydrogel showed a temperature-triggered sol-gel transition behavior and high potential for use as drug controlled release. When the surrounding temperature was close to the skin temperature of around 34 °C, it became a moisture management system where the liquids including sweat, blood, and other body fluids can be transported unidirectionally from one fabric side with the hydrophobic hydrogel coating to the untreated opposite side. This thereby showed that the thermoresponsive hydrogel-coated textile materials had a function to keep topical skin area clean, breathable, and comfortable, thus suggesting a great potential and significance for long-term skin treatment application. The structure and surface morphology of the thermoresponsive hydrogel, in vitro drug release behavior, and the mechanism of unidirectional water transport were investigated in detail. Our success in preparation of the functional textile composites will pave the way for development of various polymer- or textile-based functional materials that are applicable in the real world.

Myorelaxant effect of bee venom topical skin application in patients with RDC/TMD Ia and RDC/TMD Ib: a randomized, double blinded study.

The aim of the study was the evaluation of myorelaxant action of bee venom (BV) ointment compared to placebo. Parallel group, randomized double blinded trial was performed. Experimental group patients were applying BV for 14 days, locally over masseter muscles, during 3-minute massage. Placebo group patients used vaseline for massage. Muscle tension was measured twice (TON1 and TON2) in rest muscle tonus (RMT) and maximal muscle contraction (MMC) on both sides, right and left, with Easy Train Myo EMG (Schwa-medico, Version 3.1). Reduction of muscle tonus was statistically relevant in BV group and irrelevant in placebo group. VAS scale reduction was statistically relevant in both groups: BV and placebo. Physiotherapy is an effective method for myofascial pain treatment, but 0,0005% BV ointment gets better relief in muscle tension reduction and analgesic effect. This trial is registered with Clinicaltrials.gov NCT02101632.

TCH-007 Development of a Betamethasone (Dipropionate) Topical Emulsion 0.1% (W/W) (1Mg/G) For Cutaneous T-Cell Lymphoma

BackgroundCutaneous lymphomas are a heterogeneous group of lymphomas characterised by T and B clonal lymphoproliferative infiltrates that appear and remain confined to the skin without evidence of involvement of other...

A pharmacokinetic study of a topical anesthetic (EMLA®) in mouse soft tissue laceration

The use of topical anesthesia instead of injection of local anesthetics for managing soft tissue lacerations in the emergency situations may be a relief for both patients and surgeons. Topical anesthesia in the form of a cream eutectic mixture of local anesthetics (EMLA®) containing 2.5% lidocaine and 2.5% prilocaine has been reported as an efficient anesthetic on skin before venipuncture anesthesia and as an alternative to injection anesthesia in some minor surgery situations. The aim of this study was to compare the pharmacokinetics of EMLA® when applied in a laceration with topical skin application in the mouse. A total of 120 Albino Laboratory-bred strain mouse (BALB-c) male mice were divided into three groups with regard to application mode of EMLA®. Group A: with laceration, 48 mice; Group B: on intact shaved skin, 48 mice; Group C: control group (24 mice) with same procedures but without application of EMLA®. Blood levels were collected at 0, 10, 20, 30, 45, 60, 75, and 90 min post-EMLA® application. Plasma sample analysis was carried out by employing liquid chromatography coupled with tandem mass spectrometric (LC-MS/MS) method, and the pharmacokinetic analysis of the mouse plasma samples was estimated by standard non-compartmental methods. The pharmacokinetic parameters of lidocaine and prilocaine were significantly altered following EMLA® application to lacerated mouse skin in contrast to intact skin. The absorption of lidocaine and prilocaine was rapid following application of EMLA® to lacerated and intact mouse skin. Maximum drug plasma concentration (C(max) ) and area under the drug plasma concentration-time curve (AUC) values of lidocaine were significantly increased by 448.6% and 161.5%, respectively, following application of EMLA to lacerated mouse skin in comparison with intact mouse skin. Similarly, prilocaine's C(max) and AUC values were also increased by 384% and 265.7%, respectively, following EMLA application to lacerated mouse skin, in contrast to intact skin. Further pharmacokinetic studies on different carriers of lidocaine/prilocaine are warranted before any firm conclusions for the clinic can be drawn.

Toxico-/biokinetics of nanomaterials

Nanomaterials (NM) offer great technological advantages but their risks to human health are still under discussion. For toxicological testing and evaluation, information on the toxicokinetics of NM is essential as it is different from that of most other xenobiotics. This review provides an overview on the toxicokinetics of NM available to date. The toxicokinetics of NM depends on particle size and shape, protein binding, agglomeration, hydrophobicity, surface charge and protein binding. In most studies with topical skin application, unintentional permeation and systemic availability were not observed; permeation for some NM with distinct properties was observed in animals. Upon inhalation, low levels of primary model nanoparticles became systemically available, but many real-world engineered NM aggregate in aerosols, do not disintegrate in the lung, and do not become systemically available. NM are prone to lymphatic transport, and many NM are taken up by the mononuclear phagocyte system (MPS) acting as a depot. Their half-life in blood depends on their uptake by MPS rather than their elimination from the body. NM reaching the GI tract are excreted with the feces, but of some NM low levels are absorbed and become systemically available. Some quantum dots were not observably excreted in urine nor in feces. Some model quantum dots, however, were efficiently excreted by the kidneys below, but not above 5-6 nm hydrodynamic diameter, while nanotubes 20-30 nm thick and 500-2,000 nm long were abundant in urine. NM are typically not metabolized. Some NM cross the blood-brain barrier favored by a negative surface charge.