Cutaneous Irritation Research Articles

Vehicle Formulation Impacts Tolerability and Patient Preference: Comparison of Tretinoin Branded Lotion and Generic Cream

Topical retinoids like tretinoin are a mainstay of acne treatment but associated cutaneous irritation and drying may lead to poor adherence. As vehicle optimization can improve patient preference and adherence, tretinoin 0.05% lotion (Altreno®) was formulated using polymeric emulsion technology for uniform delivery of micronized tretinoin and moisturizing/hydrating excipients. This study compared tolerability and participant preference of a branded tretinoin 0.05% lotion versus generic cream. In this single-center, double-blind, split-face study, 25 adult females with acne were randomized to apply lotion and cream to opposite cheeks once daily for 2 weeks. Investigator-assessed skin irritation and appearance, as well as participant ratings of the products and skin sensations, were evaluated immediately after first use and after 2 weeks. At week 2, there was significantly greater erythema, scaling, and dryness (122%–144%; P<0.01 each) and decreased skin softness, smoothness, radiance, and brightness (~40% difference; P<0.01 each) on the cream-treated versus lotion-treated side of the face. More participants agreed that the lotion was gentle, comfortable/soothing, spreadable, absorbent, not sticky, and left minimal residue versus cream (range: 72%–92% vs 8%–36%). Agreement scores on skin sensations (eg, soft, not dry, less dull) were similarly higher for lotion versus cream. Overall, ~70% of participants preferred to take home the lotion over the cream. After 2 weeks of once-daily use, tretinoin 0.05% lotion was associated with less irritation and superior skin appearance/ sensation versus generic 0.05% cream, with most participants preferring the lotion over cream. These results demonstrate the importance of a well-designed vehicle formulation on tolerability and patient preference. J Drugs Dermatol. 2022;21(8): 875-880. doi:10.36849/JDD.6945.

Venlafaxine HCl Encapsulated in Niosome: Green and Eco-friendly Formulation for the Management of Pain

The goal of this experimentation was to increase the cutaneous absorption of venlafaxine HCl (VFX) encapsulated in a niosome (venlasosme) produced by an ultrasonic approach. The impact of the cholesterol:surfactant (Chol:Surf) proportion was examined to modify the venlasosme properties. Photon correlation spectroscopy, powder X-ray diffraction (PXRD), SEM, DSC, and ATR-FTIR spectroscopy were utilized to investigate the solid-state and morphology of VFX in the venlasosme. The studies revealed that increasing the level of Chol in the venlasosme increased the size of the particles. Alterations in the Chol to surfactant ratios (when Chol decreased from 2.5 to 0%) caused the zeta potential enhancement from 7.37 ± 0.67 to 15.53 ± 1.47 mV. The venlasosme with the highest cholesterol concentration (2.5%) had the highest encapsulation efficiency (approximately 63%). PXRD results revealed that VFX in venlasosme was in the amorphous form. The levels of VFX in the cutaneous layers and the receiver compartment were higher for the venlasosme gel than for VFX simple gel in the cutaneous permeability study and showed no cutaneous irritancy in rats. Furthermore, the venlasosme gel demonstrated significant antinociceptive and anti-inflammatory responses when compared to the control groups (VFX simple gel and diclofenac gel). The topical administration of the venlasosme gel also considerably increased the tail-flick and hot-plate response time when compared to the VFX simple gel, control groups, and diclofenac gel (p < 0.05). These findings suggest that niosomes can improve VFX efficacy as an antinociceptive and anti-inflammatory substance by improving the medicaments delivery to the specified site.

Topical permethrin may increase blacklegged tick (Ixodes scapularis) repellency but is associated with cutaneous irritation in horses.

To evaluate the safety of repeated applications of permethrin concentrations (0% control, 1.5%, 5%, and 10%) to the necks and faces of horses and assess the efficacy and longevity of permethrin as an equine tick repellent. 5 healthy adult Quarter Horses. Each treatment was applied to the neck of each horse (0.01 m2) 4 times a day, for up to 10 days. An 8-mm biopsy was taken to evaluate postexposure dermal responses. Any treatments that were not withdrawn were applied to a quadrant of the horse's face 4 times a day, for up to 5 days. For tick bioassays, a treatment was applied to 1 leg of a horse and 5 female blacklegged ticks (Ixodes scapularis) were evaluated as "repelled" or "not repelled" by the treatment. The bioassays were repeated up to 5 days, but treatment application took place only on the first day of the experiment. Histological results of neck biopsies indicated that more repeated exposures or higher concentrations resulted in more dermal damage. Tick bioassays showed that 5% and 10% permethrin had the greatest efficacy and longevity as a tick repellent, but the differences in tick repellency were not significant overall. While there was a nonsignificant trend of higher permethrin concentrations repelling more ticks with longer-lasting residual repellent effects, higher concentrations also produced greater skin damage after repeated exposures. These opposing findings emphasize the need for better tick prevention and control methods that balance safety and efficacy for the equine community.

Tazarotene 0.045% Lotion: A Novel Retinoid Formulation.

The aim of this study is to review the available data on efficacy and tolerability of tazarotene 0.045% lotion. A literature search of MEDLINE (PubMed) and EMBASE databases was completed in November 2021. Articles that discussed efficacy, tolerability, and pharmacology of tazarotene 0.045% lotion, written in English and published before mid-November 2021, were assessed. In two, 12-week phase III clinical trials, tazarotene 0.045% lotion had higher rates of treatment success (study 1: 25.5% and study 2: 29.6%) than individuals who received the vehicle (study 1: 13.0% and study 2: 17.3%) (both Ps < 0.001). Participants treated with tazarotene 0.045% lotion had greater least squares mean reduction in inflammatory (study 1: 55.5% and study 2: 59.5%) and noninflammatory (study 1: 51.4% and study 2: 60%) acne lesions when compared with vehicle (inflammatory acne lesions, study 1: 45.7% and study 2:49%; noninflammatory acne lesions, study 1: 41.5% and study 2: 41.6%) (P < 0.001 for studies 1 and 2). Tazarotene 0.045% lotion was well tolerated. Retinoids are first-line therapy in the treatment of acne vulgaris. However, many patients experience cutaneous irritation, which can decrease patient adherence and efficacy. Tazarotene 0.045% lotion is the first retinoid to utilize polymeric emulsion technology (PET) to efficiently distribute the medication across the skin, decreasing adverse effects while maintaining efficacy. Tazarotene 0.045% lotion is an effective and well-tolerated retinoid recently approved by the US Food and Drug Administration (FDA) for treating acne vulgaris in individuals 9 years of age and older.

Efficacy and Tolerability of a Double-Conjugated Retinoid and Alpha Hydroxy Acid Cream in Subjects With Mild to Moderate Blemish-Prone Skin.

Topical retinoids influence the rate of cellular turnover and improve skin clarity and photoaged skin. Consequent cutaneous irritation reduces adherence resulting in suboptimal outcomes. A formulation comprised of a double-conjugated molecule containing a retinoid and an alpha hydroxy acid (AHA) has been purposefully developed for individuals with blemish-prone skin. A 12-week study conducted in subjects with mild/moderate blemish-prone skin evaluated skin clarity utilizing the Investigators Global Assessment Scale (0-Clear to 4-Severe). Changes in the appearance of pores were evaluated using a 6-point scale (0-None to 5-Severe). Adverse Events (AEs) and subject satisfaction were captured. A secondary analysis evaluated visible, quantitative changes in pores. Twenty subjects enrolled; 19 subjects completed the study. Mean percent improvements in appearance from baseline in skin clarity were demonstrated at weeks 4 (43%; P&lt;.0001), 8 (48%; P&lt;.0001) and 12 (50%; P&lt;.0001). Mean percent visible improvements from baseline in pores were observed at 4, 8, and 12 weeks (33% [P&lt;.0001]; 21% [P=.04] and 25% [P=.0006], respectively). AEs were mild and transient. By 8 weeks, all subjects reported improvement in overall appearance and that their skin was healthier looking. Secondary quantitative analysis (n=6) demonstrated an 18% mean improvement in the appearance of pores from baseline at week 12. A double-conjugated retinoid/AHA cream specifically developed for individuals with blemish-prone skin demonstrated early improvements in the appearance of skin clarity and pores over 12 weeks. AEs were mild and transient. Subjects reported high levels of satisfaction in the overall appearance and quality of skin. J Drugs Dermatol. 2022;21(1):54-59. doi:10.36849/JDD.6415.

Efficacy and Tolerability of a Double-Conjugated Retinoid and Alpha Hydroxy Acid Cream in Subjects With Mild to Moderate Blemish-Prone Skin

Background: Topical retinoids influence the rate of cellular turnover and improve skin clarity and photoaged skin. Consequent cutaneous irritation reduces adherence resulting in suboptimal outcomes. A formulation comprised of a double-conjugated molecule containing a retinoid and an alpha hydroxy acid (AHA) has been purposefully developed for individuals with blemish-prone skin. Design and Methods: A 12-week study conducted in subjects with mild/moderate blemish-prone skin evaluated skin clarity utilizing the Investigators Global Assessment Scale (0-Clear to 4-Severe). Changes in the appearance of pores were evaluated using a 6-point scale (0-None to 5-Severe). Adverse Events (AEs) and subject satisfaction were captured. A secondary analysis evaluated visible, quantitative changes in pores. Results: Twenty subjects enrolled; 19 subjects completed the study. Mean percent improvements in appearance from baseline in skin clarity were demonstrated at weeks 4 (43%; P<.0001), 8 (48%; P<.0001) and 12 (50%; P<.0001). Mean percent visible improvements from baseline in pores were observed at 4, 8, and 12 weeks (33% [P<.0001]; 21% [P=.04] and 25% [P=.0006], respectively). AEs were mild and transient. By 8 weeks, all subjects reported improvement in overall appearance and that their skin was healthier looking. Secondary quantitative analysis (n=6) demonstrated an 18% mean improvement in the appearance of pores from baseline at week 12. Conclusions: A double-conjugated retinoid/AHA cream specifically developed for individuals with blemish-prone skin demonstrated early improvements in the appearance of skin clarity and pores over 12 weeks. AEs were mild and transient. Subjects reported high levels of satisfaction in the overall appearance and quality of skin. J Drugs Dermatol. 2022;21(1):54-59. doi:10.36849/JDD.6415Double-Conjugated Retinoid

Micro-structural investigations on oppositely charged mixed surfactant gels with potential dermal applications

Dicarboxylic amino acid-based surfactants (N-dodecyl derivatives of -aminomalonate, -aspartate, and -glutamate) in combination with hexadecyltrimethylammonium bromide (HTAB) form a variety of aggregates. Composition and concentration-dependent mixtures exhibit liquid crystal, gel, precipitate, and clear isotropic phases. Liquid crystalline patterns, formed by surfactant mixtures, were identified by polarizing optical microscopy. FE-SEM studies reveal the existence of surface morphologies of different mixed aggregates. Phase transition and associated weight loss were found to depend on the composition where thermotropic behaviours were revealed through combined differential scanning calorimetry and thermogravimetric studies. Systems comprising more than 60 mol% HTAB demonstrate shear-thinning behaviour. Gels cause insignificant toxicity to human peripheral lymphocytes and irritation to bare mouse skin; they do not display the symptoms of cutaneous irritation, neutrophilic invasion, and inflammation (erythema, edema, and skin thinning) as evidenced by cumulative irritancy index score. Gels also exhibit substantial antibacterial effects on Staphylococcus aureus, a potent causative agent of skin and soft tissue infections, suggesting its possible application as a vehicle for topical dermatological drug delivery.

O83: COMPASS – MANAGEMENT OF COMPLICATED INTRA-ABDOMINAL COLLECTIONS AFTER COLORECTAL SURGERY, A EUROSURG COLLABORATIVE INTERNATIONAL STUDY

Abstract Presenting Author Email: ruthblancocolino@gmail.com Research question To explore current practices on the use of prophylactic postoperative drains in colorectal surgery and whether it influences 30-day postoperative outcomes. Background and aim Traditionally, postoperative drains have been used in colorectal surgery for the prevention or early detection of intraabdominal collections. However, current evidence suggests there is no clear clinical benefit to prophylactic drain placement following colorectal surgery, and Enhanced Recovery After Surgery (ERAS) guidelines recommend against their routine use. Nevertheless, a previous international audit by Eurosurg (Ileus Management International) found more than a third of participating centres routinely placed a drain in more than half of their patients. Therefore, this study aims to audit compliance to ERAS guidelines regarding the use of postoperative drains in colorectal surgery. Design Patients Adult patients undergoing elective and emergency colorectal surgery will be included. Procedures under any surgical approach including any formation of colostomy or ileostomy, resection of large bowel, or reversal of stoma will be eligible. Patients undergoing appendicectomy, transanal surgery, primarily urological, gynaecological or vascular procedure, surgery involving multivisceral resection, diagnostic laparotomy or laparoscopy or hernia surgery without colorectal resection, will be excluded. Comparator Group of patients receiving a prophylactic drain after surgery. Main explanatory variable will be intrabdominal collections rate including anastomotic leak. Outcomes The primary outcome measure will be the adherence to selected ERAS guidelines regarding rate of routine prophylactic drain insertion in colorectal surgery. As Secondary outcome measures we will assess: • Rate of intra-abdominal postoperative collections, defined as collections which alter the normal postoperative course (e.g. requiring either medical, radiological, endoscopic or surgical intervention). • Time-to-diagnosis (days) of intra-abdominal postoperative collections defined as collections which alter the normal postoperative course. • Rate of drain-related complications defined as: surgical site infection by Centers for Disease Control and Prevention definition; cutaneous irritation at the drain insertion site; small bowel evisceration and herniation of omentum, bowel injury (defined as intraoperative identification of or CT-proven drain-related iatrogenic bowel perforation); time (measured in whole days) until drain removal and drain output (quantity and contents) on day of removal; and overall 30-day adverse event rate as defined by the Clavien-Dindo scale of postoperative complications and length of stay (days). Study design This is a prospective, multicentre, audit that will be conducted through the student- and trainee-led EuroSurg collaborative network across Europe, South Africa and Australasia. Data will be collected on consecutive 14-day periods, from 3rd February to 26th April 2020, with 30-day follow-up on included patients. Data will be collected online on REDCap database based on Birmingham University. Team and infrastructure The study will be run by the European Student Research Collaborative. EuroSurg is a pan-European student- and trainee-led surgical which also counts with international collaboration from Australia, New Zealand and South Africa. The study will be coordinated by the International Study Management Group and at each participating country, there will be a core of national leads or national collaborative in charge of organising the study locally. Each hospital will count with a Local Lead who will coordinate the mini-teams based at their centre and will be in contact with its corresponding National Leads. A mini-team will be composed by three collaborators collecting data and a supervising consultant per centre. As infrastructure for leading the project, we will use social media for study diffusion including Twitter, Facebook, Instagram and LinkedIn, and emails through Gmail official account and Mailchimp. Management group communications will be held through WhatsApp, Slack and Skype.

Effective lightening of facial melasma during the summer with a dual regimen: A prospective, open‐label, evaluator‐blinded study

Melasma is a chronic pigmentary condition that can have significant negative effects on quality of life. Vitamin C can be effective in the treatment melasma, but its delivery often proves to be challenging due to instability of the drug and subsequent cutaneous irritation at higher concentrations. In this prospective, open-label, evaluator-blinded study, we aimed to assess the efficacy and tolerability of twice-daily application of a novel, highly potent, non-irritating 30% tetrahexyldecyl (THD) ascorbate serum in combination with 100% mineral-based sunscreen in the treatment of melasma during the summer months. Ten female subjects of ages ranging from 18 to 60years underwent twice-daily application of 30% THD ascorbate serum in combination with an anti-aging 100% mineral tinted broad-spectrum protection SPF 45 sunscreen moisturizer for 12weeks during the summer months (July to September). Two blinded evaluators scored baseline and post-treatment photographs using the Griffiths' 10-point scale and global aesthetic improvement scale. All subjects showed an improvement in hyperpigmentation with an average improvement of 33.7%. Seventy percent of subjects showed an improvement in skin tone evenness (redness), and among those subjects, the average improvement was 33.3%. The median global aesthetic improvement score was 2.0 (very much improved). Our study demonstrated efficacy and safety in treating the pigmentary as well as vascular components of melasma with a novel 30% THD ascorbate serum and a purely mineral-based tinted moisturizing sunscreen.

Developing an Efficacious Diclofenac Diethylamine Transdermal Formulation

The aim of current study was to develop an efficacious topical formulation of diclofenac diethylamine (DDA), for eventual use as a locally applied analgesic lotion. A series of lotions were prepared that incorporated 2% w/v DDA but a variable (1, 2, 3 or 4% v/v) concentration of oleic acid (permeation enhancer)-turpentine oil binary mixture (1:1 v/v). After measurements of each lotion's visual appearance, viscosity, spreadability, pH and long term stability, a diffusion cell method was employed to quantify DDA permeation from each lotion across both silicone membranes and rabbit skin. Subsequently, three distinct in vivo animal models were utilised to evaluate each lotion's induced anti-inflammatory, antinociception and irritancy effects. Lastly, a panel of human volunteers assessed the subjective sensory feel of each lotion as well as its potential for cutaneous irritancy following a brief application. Upon preparation, all four DDA-containing lotions (L1, L2, L3 and L4) appeared as clear, colourless, homogenous and aggregate-free solutions. All the lotions exhibited a pH of ~6.2 with non-significant (p ＞ 0.05) differences between each formulation (data not shown). Increasing the formulation's oleic acid concentration yielded a general trend of mild enhancement of DDA transport across silicone membrane and dramatic improvements of DDA flux through rabbit skin. Application of each of the DDA-containing formulations significantly reduced tissue inflammation in the rabbit model. It was determined that the DDA lotion containing 4% v/v oleic acid exhibited the best performance overall and that this specific formulation should be the basis for further clinical investigation.

Abstract 182: Orally Administered 9-cis Retinoid Acid Improves Functional Lymphatic Drainage In Post-surgical Lymphedema

Purpose: We have previously shown that daily intraperitoneal administration of 9-cis Retinoic Acid (9-cis RA) is associated with increased lymphangiogenesis and lymphatic clearance in a mouse tail model of lymphedema. Since an oral dosing regimen would have higher clinical translatability, we sought to determine if orally administered 9-cis RA was similarly effective in preventing lymphedema. Methods: In a mouse tail model, secondary lymphedema was induced by excising 5 mm of skin circumferentially and obliterating all remaining lymphatics utilizing injection of methylene blue and the operative microscope. Twenty-five sex-matched FVB mice aged weighing between 20 and 30 grams were assigned to one of three groups: control (n=8), low-dose 9-cis RA (n=8), and high-dose 9-cis RA (n=9). 9-cis retinoic acid was dissolved in soybean oil, and vehicle control consisted of soybean oil. Low-dose 9-cis RA mice and high-dose 9-cis RA mice received doses of 10 mg/kg and 30 mg/kg respectively, and each mouse was given 0.15 mL of solution via oral gavage daily. The tail images were taken every week for 6 weeks and analyzed with ImageJ software. On POD42, mice tails were injected intradermally with indocyanine green (ICG), and fluorescence was captured and quantified via NOVADAQ Spy Fluorescence Imaging at 0, 1, 3, 6, 12, 24, 48, 72, and 96 hours. Lastly, a comprehensive metabolic panel was performed on the blood serum of each mouse. Results: The percentage change in tail volume of the low 9-cis RA group was statistically lower than the control group at all time points beginning on POD14 (p < 0.05). At POD14, the mean change in tail volume for the low 9-cis RA group and control groups were 18.11% and 69.26% respectively (p < 0.001). The percentage change in fluorescence from hour 1 post-ICG injection was significantly different between low-dose 9-cis RA group and the control group at 72, 96, and 120 hours (p < 0.05). The high-dose 9-cis RA group did not show a significant difference in tail volume change or fluorescence change relative to the control group. In addition, the high-dose 9-cis RA group demonstrated mild cutaneous irritation in the perioral and throat regions while these adverse events were not observed in the low-dose 9-cis RA group. The chemistry panel results showed no significant differences between control and both 9-cis RA groups, and there was no significant difference in weights for any groups at any time point. Conclusion: Treatment with orally administered 9-cis RA at an oral dose of 10 mg/kg attenuates the volume change associated with lymphedema and improves lymphatic drainage in a mouse tail model. These findings offer a potential preventative treatment for patients at risk of developing secondary lymphedema.

Topical Proretinal Nanoparticles: Biological Activities, Epidermal Proliferation and Differentiation, Follicular Penetration, and Skin Tolerability

Proretinal nanoparticles, the retinilidene-chitosan nanoparticles, have been developed to overcome the physicochemical instability of retinal and to lessen the dose-dependent cutaneous irritation, through sustaining the release of retinoid. Compared to conventional retinal at the same concentration, proretinal nanoparticles had no cytotoxicity and could induce a spontaneously immortalized human keratinocyte line to express more cellular retinoic acid binding protein-2. Compared to rats topically applied with conventional retinal which showed clear skin irritation and inflammation, daily topical application of proretinal nanoparticles to rats for 28 consecutive days produced neither irritation nor inflammation but significantly increased epidermal proliferation, epidermal thickness, cellular retinoic acid binding protein- 2 expression, and up-regulation of various differentiation markers including keratin 5, keratin 10, keratin 14, cellular retinoic acid binding protein-2, and proliferating cell nuclear antigen. Through the use of confocal laser scanning microscopy, we observed the in vivo follicular penetration of proretinal nanoparticles with the depth of penetration independent of postapplication time. Proretinal nanoparticles provide better biological activities of retinoids on epidermis and could eliminate the side effect of retinoid dermatitis.

Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris: assessment of safety and tolerability in subgroups

Background: Topical tretinoin’s role in acne has been established through evidence-based guidelines. Cutaneous irritation and potential to cause or exacerbate postinflammatory hyperpigmentation (PIH) may limit use.Objective: Evaluate safety and tolerability of novel polymeric formulation of tretinoin 0.05% lotion in moderate-to-severe acne.Methods: One thousand six hundred and forty patients randomized to tretinoin 0.05% lotion or vehicle in two double-blind placebo-controlled 12-week studies. Investigator-evaluated cutaneous safety (erythema and scaling) and patient-reported tolerability (itching, burning/stinging) assessed using a scale of 0 (none) to 3 (severe). Hyper- and hypo-pigmentation evaluated at each study visit. A number of subpopulations were investigated.Results: Tretinoin 0.05% lotion was considered safe and very well tolerated. Only application site pain (3.1%), dryness (3.7%) and erythema (1.4%) were reported by >1% or patients. Treatment-related adverse events were particularly rare (≤2%) in Hispanic and male subpopulations, and lower in adult females. The severity of cutaneous safety and tolerability scores remained <0.5 (where 1 = mild) and were generally lower than baseline severity. Tretinoin 0.05% lotion did not appear to cause or exacerbate PIH.Conclusions: A novel polymeric formulation of tretinoin 0.05% lotion provides a highly favorable safety and tolerability profile, with an incidence of erythema, dryness, and skin burning lower than that previously reported with other formulations of tretinoin.

Complications following minimally invasive internal fixation for anterior pelvic ring injury: a Meta-analysis

Objective To summarize the complications and their incidences following Anterior Sub-cutaneous Internal Pelvic Fixation(ASIPF). Methods A comprehensive search was conducted of PubMed Library, Cochrane Library, Web of Science, SinoMed, Wanfang Data and China National Knowledge Internet for all articles addressing the postoperative complications of ASIPF published in English and Chinese from January 2009 to November 2018. A proportion Meta-analysis across the studies was performed for the complications after ASIPF (lateral femoral cutaneous nerve irritation, femoral nerve palsy, heterotopic ossification, infection and implant failure) using R software. Results This meta-analysis included 29 clinical studies involving a total of 825 patients. The complications following ASIPF were lateral femoral cutaneous nerve irritation, femoral nerve palsy, heterotopic ossification, infection and implant failure; their incidences were respectively 12% (95%CI: from 7% to 19%), 3% (95%CI: from 2% to 4%), 30% (95%CI: from 22% to 39%), 4% (95%CI: from 3% to 6%) and 4% (95%CI: from 3% to 6%). Conclusions Lateral femoral cutaneous nerve irritation and heterotopic ossification are common complications following minimally invasive internal fixation for anterior pelvic ring injury. High-quality clinical research is needed into the factors leading to the complications and into their preventive countermeasures. Key words: Pelvis; Fractures, bone; Fracture fixation, internal; Surgical procedures, minimally invasive; Complications

Cutaneous Scarring

Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloid and hypertrophic scarring. This suggests that these pathologic scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. Various external and internal postwounding stimuli may promote reticular inflammation. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. At present, physicians cannot (or at least find it very difficult to) control systemic and genetic risk factors of keloids and hypertrophic scars. However, they can use a number of treatment modalities that all, interestingly, act by reducing inflammation. These include corticosteroid injection or tape or ointment, radiotherapy, compression therapy, stabilization therapy, and surgical methods that reduce skin tension. This review contains 11 figures and 41 references. Key Words: atrophic scar, hypertrophic scar, keloid, mature scar, pathologic scar, wound healing

Cutaneous Scarring

Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloid and hypertrophic scarring. This suggests that these pathologic scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. Various external and internal postwounding stimuli may promote reticular inflammation. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. At present, physicians cannot (or at least find it very difficult to) control systemic and genetic risk factors of keloids and hypertrophic scars. However, they can use a number of treatment modalities that all, interestingly, act by reducing inflammation. These include corticosteroid injection or tape or ointment, radiotherapy, compression therapy, stabilization therapy, and surgical methods that reduce skin tension. This review contains 11 figures and 41 references. Key Words: atrophic scar, hypertrophic scar, keloid, mature scar, pathologic scar, wound healing

Nanotechnological Advances for Cutaneous Release of Tretinoin: An Approach to Minimize Side Effects and Improve Therapeutic Efficacy.

The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. Through bibliographic research in databases we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy.

Development and characterization of a nanoemulsion containing propranolol for topical delivery.

BackgroundPropranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo.MethodsThe formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m.ResultsNE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of −20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay.ConclusionWe concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas.

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers

ABSTRACTObjectives: To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster.Methods: This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40.Results: The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38.Conclusions: The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.

Garlic-A Golden Wonder

Garlic belongs to the family of Allium which produce organosulfur compounds like allicin and diallyl disulfide (DADS) which give its pungent as well as spicy aroma. It’s benefits have been attributed to hypotensive and vasorelaxant activities. It has also been found that chronic Helicobacter pylori is reduced with Allium vegetable intake. Garlic preparations are widely available as garlic powder (GP) or garlic oil (GO). Epidemiological studies have shown a close link between stomach cancer, H. pylori infection and the consumption of Allium vegetables. Since a long time, garlic has been used as herbal medicines for treating a variety of ailments like hypertension, high blood cholesterol and thrombosis. At the same time, it can also produce adverse effects such as cutaneous irritation, edema and allergic contact dermatitis.