CYCLOMETHICONE

In the treatment of human head lice infestation, healthcare providers are increasingly concerned about lice becoming resistant to existing pesticide treatments. Traditional pesticides, used to control these pests, have a neurological mechanism of action. This publication describes a topical solution with a non-traditional mechanism of action, based on physical disruption of the wax layer that covers the cuticle of the louse exoskeleton. This topical solution has been shown clinically to cure 82% of patients with only a 10-minute treatment time, repeated once after 7 days. All insects, including human head lice, have a wax-covered exoskeleton. This wax, composed of hydrocarbons, provides the insect with protection against water loss and is therefore critical to its survival. When the protective wax is disrupted, water loss becomes uncontrollable and irreversible, leading to dehydration and death. A specific pattern of hydrocarbons has been found in all of the head louse cuticular wax studied. Iso-octane effectively removes these hydrocarbons from human head lice's cuticular wax. A method of head louse cuticle wax extraction and analysis by gas chromatography was developed. Human head lice (Pediculus humanus capitis) were collected from infested patients and subjected to any of three extraction solvents comprising either the test product or one of two solvents introduced as controls. A gas chromatograph equipped with a flame ionization detector (GC/FID) was used to determine the presence of hydrocarbons in the three head lice extracts. In the study reported herein, the test product isopropyl myristate/cyclomethicone D5 (IPM/D5) was shown to perform comparably with iso-octane, effectively extracting the target hydrocarbons from the cuticular wax that coats the human head louse exoskeleton. Disruption of the integrity of the insect cuticle by removal of specific hydrocarbons found in the cuticular wax appears to offer a mechanism for killing lice without the likelihood of encountering genetic resistance.

Cyclomethicone (mixture) and the specific chain length cyclic siloxanes (n = 4-7) reviewed in this safety assessment are cyclic dimethyl polysiloxane compounds. These ingredients have the skin/hair conditioning agent function in common. Minimal percutaneous absorption was associated with these ingredients and the available data do not suggest skin irritation or sensitization potential. Also, it is not likely that dermal exposure to these ingredients from cosmetics would cause significant systemic exposure. The Cosmetic Ingredient Review Expert Panel concluded that these ingredients are safe in the present practices of use and concentration.

Bacterial folliculitis, commonly associated with  Staphylococcus aureus , often stems from trauma to hair follicles, such as during waxing, and can be exacerbated by improper aftercare that triggers inflammation and skin damage. This report describes a 23-year-old man with widespread folliculitis, mainly concentrated in the lower back, with involvement of the arms and entire back, post-waxing, aggravated by alcohol and soap use. He initially experienced high fever, trouble sleeping, discomfort when lying down, and strong itching, with the fever subsiding after a couple of days. He self-medicated with ibuprofen and diphenhydramine for five days without relief, followed by ineffective prescribed treatments with mupirocin and hydrocortisone. Adding oral azithromycin and Tend Skin® solution (isopropyl alcohol, water, propylene glycol, acetylsalicylic acid, cyclomethicone, glycerin, polysorbate 80) brought significant symptom relief, reduced pustule size, and less exudate within days. This case highlights the efficacy of combined systemic and topical therapies for refractory folliculitis and underscores the importance of proper post-waxing care to curb inflammation and skin damage.

To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM-TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM-TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 μM BIM, equivalent to 10 μM minoxidil. Moreover, BIM-TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM-TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM-TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM-TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.

In this study, a stable and highly skin-permeable topical delivery system for itraconazole (ITZ) was designed to provide effective treatment against superficial mycosis. Herein, ITZ was incorporated into a solution composed of ethanol, benzyl alcohol, hydrochloric acid, Transcutol P, and cyclomethicone as a delivery vehicle, solubilizer, protonating agent, permeation enhancer, and spreading agent, respectively. At 72 h, the optimal topical ITZ formulation (ITZ-TF#11) exhibited 135% enhanced skin permeability, which led to increases in drug deposition in the stratum corneum, epidermis, and dermis of 479%, 739%, and 2024%, respectively, compared with the deposition of 1% ITZ in ethanol (control). Moreover, on day 7, ITZ-TF#11 demonstrated 2.09- and 2.30-fold enhanced nail flux and drug deposition, compared with the control. At a dose of 40 mg/kg/day, ITZ-TF#11 showed 323% greater lesion recovery, a 165% lower mean erythema severity score, and a 37% lower mean logarithm of viable fungal cells in skin in the treated area, compared with mice that received oral ITZ at the same dose. Overall, the findings imply that ITZ-TF#11 is a superior alternative to oral ITZ for treatment of superficial mycosis.

Onychomycosis is a progressive fungal infection of the nails that involves the deeper nail layer and nail bed. It is important to maintain sufficient drug concentration in the diseased tissues after topical application. In this study, a stable topical delivery system for efinaconazole (EFN) was designed to enhance absorption potential through the skin and nail plate by incorporating ethanol, diethylene glycol monoethyl ether (Transcutol P) and isopropyl myristate, and cyclomethicone into the topical solution as a delivery vehicle, permeation enhancers, and a wetting agent, respectively. In addition, the stability of EFN in the formulation was significantly improved by adding butylated hydroxytoluene, diethylenetriamine pentaacetic acid, and citric acid as an antioxidant, chelating agent, and pH-adjusting agent, respectively, without discoloration. The optimum EFN formulation (EFN-K) showed 1.46-fold greater human skin permeation than that of the reference control (commercial 10% EFN topical solution). Furthermore, after a 24-hour incubation, the amount of infiltrated EFN from EFN-K in the human nail plate was 4.11-fold greater than that of the reference control, resulting in an 89.7% increase in nail flux at 7 days after treatment. EFN-K significantly accelerated structural recovery of the keratin layer in a Trichophyton mentagrophytes -infected guinea pig onychomycosis model, decreasing the mean viable fungal cell count by 54.3% compared to the vehicle-treated group after once-daily treatment for 4 weeks. Thus, the accelerated skin and nail penetration effect of EFN-K is expected to achieve good patient compliance, and improve the complete cure rate of onychomycosis.

Dermal absorption of components of personal care products (PCPs) may contribute to breast cancer development. Cyclic volatile methylsiloxanes (cVMS) are used widely in the formulation of PCPs, and their presence has been recently detected in human blood. The objectives of this study were to investigate any genotoxic effects after short- (1 week) or longer-term (30 weeks) exposure to hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) or decamethylcyclopentasiloxane (D5) in MCF-10 A and MCF-10F immortalized non-transformed human breast epithelial cells. Genotoxic effects were assessed by an ability of cells to grow in suspension culture, from DNA damage measured by comet assays, and from a reduction in levels of DNA repair proteins measured by RT-PCR and western immunoblotting. Dose-dependent anchorage-independent growth in methocel culture was observed after exposure to D3 (10 - 13  M-10 -5  M) and D4/D5 (10 - 9  M-10 -5  M). DNA damage was measured by the comet assay after 1-h exposure to D3 (10 - 6  M-10 -5  M) and D4 (10 -5  M). BRCA1 mRNA and BRCA1 protein levels were reduced after 30-week exposure to 10 -5  M D4 and D5 in both cell lines. Reduced levels of mRNAs for other DNA repair proteins (BRCA2, ATM, ATR, CHK1 and CHK2) were also observed after exposure to 10 -5  M D5 in both cell lines, and some reductions after exposure to D3 and D4. If cVMS can not only enable anchorage-independent growth of non-transformed breast epithelial cells and damage DNA, but also compromise DNA repair systems, then there is the potential for them to impact on breast carcinogenesis. Further risk assessment now requires information concerning the extent to which cVMS may be present in human breast tissues. Copyright © 2016 John Wiley & Sons, Ltd.

The type of material stabilized by four kinds of fluorinated particles (sericite and bentonite platelet clays and spherical zinc oxide) in air-oil mixtures has been investigated. It depends on the particle wettability and the degree of shear. Upon vigorous agitation, oil dispersions are formed in all the oils containing relatively large bentonite particles and in oils of relatively low surface tension (γla < 26 mN m(-1)) like dodecane, 20 cS silicone, and cyclomethicone containing the other fluorinated particles. Particle-stabilized oil foams were obtained in oils having γla > 26 mN m(-1) where the advancing air-oil-solid contact angle θ lies between ca. 90° and 120°. Gentle shaking, however, gives oil-in-air liquid marbles with all the oil-particle systems except for cases where θ is <60°. For oils of tension >24 mN m(-1) with omniphobic zinc oxide and sericite particles for which advancing θ ≥ 90°, dry oil powders consisting of oil drops in air which do not leak oil could be made upon gentle agitation up to a critical oil:particle ratio (COPR). Above the COPR, catastrophic phase inversion of the dry oil powders to air-in-oil foams was observed. When sheared on a substrate, the dry oil powders containing at least 60 wt % of oil release the encapsulated oil, making these materials attractive formulations in the cosmetic and food industries.

We previously reported nonaqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc (MVC). Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). MVC and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard HEC vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e., as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides.

Low molecular weight cyclic volatile methylsiloxanes (cVMSs) are widely employed as emollients and carrier solvents in personal care formulations in order to acquire desired performance benefits owing to their distinctive physicochemical properties. Under current European legislation cosmetic ingredients such as cVMSs are required to be labeled on the product package only qualitatively, while for the assessment of environmental and consumer exposure quantitative information is needed. The aim of this study was therefore to measure concentrations of three cVMSs, namely octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6) in 51 cosmetics and personal care products (C&PCPs) that are currently available on the European market. The list of selected articles comprised a variety of hair and sun care products, skin creams and lotions, deodorants including antiperspirants, liquid foundations and a toothpaste. The target compounds were extracted from the products with different organic solvents dependent on the product matrix, followed by gas chromatography analysis with flame ionization detection (GC-FID). D5 was the predominant cVMS with the highest mean and median concentrations in all the C&PCP categories. The median concentrations of D5, D6 and D4 were 142, 2.3 and 0.053 mg/g in deodorants/antiperspirants (n = 11); 44.6, 30.0mg/g and below the limit of quantification (<LOQ; LOQ for D4 = 0.00071 mg/g) in cosmetics (n = 5); 8.4, 0.32 mg/g and <LOQ in skin care (n = 16); 9.6, 0.18 and 0.0055 mg/g in hair care (n = 10); and, 34.8, 0.53 and 0.0085 mg/g in sun care (n = 8) products, respectively. The calculated median aggregate daily dermal exposure to D4 and D5 from multiple C&PCPs was approximately 100 times lower than the current NOAEL derived from chronic inhalation rat studies.

Tocopheryl acetate is viscous oily fluid used in a range of preparations for skin and scalp care in Italy. Observational and in vitro data have suggested a high level of efficacy against head louse infestation. The purpose of this investigation was to confirm the activity of tocopheryl acetate in a clinical setting in comparison with a standard widely used preparation. A spray formulation containing tocopheryl acetate 20% in cyclomethicone was compared with permethrin 1% creme rinse for treatment of head louse infestation in a randomised, assessor blind, trial. Forty-five people were treated on two occasions 7 days apart. The spray was applied to dry hair for 20 minutes then washed. Participants treated with permethrin washed their hair and towel dried it before treatment for 10 minutes. Assessments were made by dry detection combing 1, 6, 9, and 14 days after first treatment. The tocopheryl acetate 20% spray was significantly (p = 0.033) more effective than permethrin 1%, using intention to treat worst case analysis, in which there were 13/23 (56.5%) successful treatments for tocopheryl acetate compared with 5/22 (22.7%) for permethrin. After unprecedented issues of re-infestation within households had been taken into account the underlying cure rate was 17/23 (73.9%) for tocopheryl acetate compared with 5/22 (22.7%), Odds Ratio 9.63 (95% CI, 2.46 to 37.68) (p < 0.001). The tocopheryl acetate spray was significantly more effective than the permethrin product, was cosmetically acceptable, and not affected by current problems with resistance. Current Controlled Trials ISRCTN45553737.

This study investigated the effects of a skin protectant solution (dimethicone 2%) on clinical signs and skin barrier function in canine atopic dermatitis (AD). Eighteen dogs with AD were randomly divided into two groups, one received dimethicone and the other received the vehicle (cyclomethicone) on selected areas (pinnae, groin, and axillae) daily for 4 weeks. Owners and investigators were blinded regarding group allocation. Clinical efficacy was evaluated using a scoring system and skin barrier by measuring the transepidermal water loss. Twelve dogs completed the study (50% drop rate in the vehicle and 20% in the dimethicone). For clinical signs, analysis of variance showed an effect of time (P < 0.005; day 0 > day 28) and region (axillae < groin < pinnae) but no effect of group or group × time interaction. For transepidermal water loss, analysis of variance showed only a main effect of region (axillae > pinnae > groin). Pearson found no correlation between transepidermal water loss and clinical scores. In this pilot study dimethicone had no significant effect on clinical signs and transepidermal water loss in canine atopic dermatitis.