Skin irritation potential of cosmetic preservatives: An exposure‐relevant study

Objective: The aim of the present study was to design nanocarriers for the topical application of rivastigmine. Methods: The effect of cosurfactants, hydrophilic gel and loading amount on the permeability of rivastigmine through rat skin was evaluated. Skin irritation tests and stability tests were performed to evaluate the utility of tested formulations. Results: The results showed that the microemulsion formation and characteristics of drug-loaded formulations were related to many parameters of the components. When using microemulsion systems as a vehicle, the permeation rate remarkably increased about 13.2~24.3-fold and the lag time was significantly shortened from 24 h to 4.7 h. Formulations containing a cosurfactant of Diethylene Glycol Monobutyl Ether (DEGBE) showed higher enhancement effect, while increasing the loading dose from 0.5% to 5% further increased the flux about 2.1-fold and shortened the lag time. Conclusion: The drug-loaded experimental formulation did not cause skin irritation and had good stability at 20ºC and 40ºC storage for at least 3 months. The result showed that gel-based microemulsion formulation could be a promising approach for topical administration.

Download Full-text

Development and Evaluation of Particulate Microcarriers of Adapalene as a Topical Delivery System

Drug Delivery Letters ◽

10.2174/2210303109666190227163606 ◽

2019 ◽

Vol 9 (3) ◽

pp. 222-233

Author(s):

Divya D. Jain ◽

Namita D. Desai

Keyword(s):

Patient Compliance ◽

Targeted Delivery ◽

Ex Vivo ◽

Acne Vulgaris ◽

Drug Loading ◽

Topical Therapy ◽

Skin Irritation ◽

Topical Delivery ◽

Diffusion Method ◽

Topical Gel

Background: Adapalene is a promising third generation retinoid used in the topical treatment of acne vulgaris. However, the major drawback associated with conventional topical therapy of Adapalene is the ‘retinoid reaction’ which is dose-dependent and characterized by erythema, scaling and burning sensation at the application sites. Microparticulate drug delivery can play a major role in reducing side effects and providing better patient compliance due to targeted delivery. Methods: Adapalene microparticles were prepared using quasi emulsion solvent diffusion method. The effects of formulation variables including polymer ratios, amounts of emulsifier, drug loading and process variables such as stirring time and speed on the physical characteristics of microparticles were investigated. The developed microparticles were characterized by DSC and SEM. Adapalene microparticles were incorporated into Carbopol 971 NF gel for ease of topical delivery. Results: Adapalene microparticulate topical gel showed sustained drug release over 8 hours in in vitro studies. The amount of drug retained in the rat skin during ex vivo studies was higher in the microparticulate topical gel (227.43 ± 0.83 µg/cm2) as compared to the marketed formulation (81.4 ± 1.11 µg/cm2) after 8 hours indicating localized and sustained drug action that can be useful in treating acne vulgaris. The safety of optimized Adapalene gel determined by skin irritation studies performed on Sprague Dawley rats showed no irritation potential. Conclusion: Microparticles can provide promising carrier systems to deliver Adapalene, improving patient compliance due to enhanced skin deposition, localized and sustained action with reduced associated irritant effects.

Download Full-text

Berberine Chloride Dihydrate Enthused Nanovesicles for the Management of Dermatitis

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681210666200313123550 ◽

2020 ◽

Vol 10 ◽

Author(s):

Nimisha Srivastava ◽

Zeeshan Fatima ◽

Chanchal Deep Kaur ◽

Dilshad Ali Rizvi

Keyword(s):

Laser Scanning ◽

Skin Irritation ◽

Research Work ◽

Slight Modification ◽

Entrapment Efficiency ◽

Laser Scanning Microscopy ◽

Confocal Laser ◽

Chloride Dihydrate ◽

E Coli ◽

Berberine Chloride

Background: Dermatitis is a common inflammatory skin disease that is affecting up to 25% of children and 1%-3% of adults worldwide. Paucity of exact cure for dermatitis and untoward side effects of topical immunosuppressive steroids has resulted into a great need for making use of complementary medicine to treat dermatitis. Objective: The present research work involved the development of Berberine chloride dihydrate (BCD) enthused nanovesicles i.e. ethosomes for the management of dermatitis. Method: Ethosomes were prepared by slight modification of cold method using varying concentrations of SPC (1-3%) and ethanol (10-40%) Optimized batch BCD 12 was further added to Carbopol 934P for gel formation. GEL BCD 12 was subjected to “anti-bacterial, dermatitis and skin irritation study. Result: The vesicles were in size range 142.42-398.31 nm while polydispersity index (PDI) ranges from 0.114-1.56 and for zeta potential it was from-18.8 to -39.4. Entrapment efficiency was from 46.05-88.79 %. Confocal laser scanning microscopy showed penetration depth of rhodamine enthused ethosome across rat skin upto 110 µm which was significantly higher than rhodamine solution (10 µm). In the anti-bacterial study, BCD loaded ethosomal gel (EG) showed maximum zone of inhibition of 18.5 mm against E. coli, 14.5 mm against P. aeruginosa and 23.0 mm against S. aureus. In dinitrochlorobenzene (DNCB) induced mice dermatitis model histopathology study showed marked decrease in amount of inflammatory cell nucleus in mice treated with BCD loaded ethosomal gel followed by 56% and 50 % increase in ear swelling and ear mass respectively in morphology study. Conventional marketed formulation showed nominal decrease in epidermal thickness, 66.67 % increase in ear thickness and 63.64 % increase in ear mass. Further Primary irritation index was less than 0.4 indicating negligible irritation in all the groups. Conclusion: It can be concluded that ethosomal gel is not only an efficient carrier for BCD but also proves its potential for the management of dermatitis.

Download Full-text

Safety Evaluation of Eucalyptus globulus Essential Oils through Acute and Sub-acute Toxicity and Skin Irritation in Mice and Rats

Current Chemical Biology ◽

10.2174/2212796814999200818095036 ◽

2020 ◽

Vol 14 (3) ◽

pp. 187-195

Author(s):

Berhan Mengiste ◽

Tizazu Zenebe ◽

Kassahun Dires ◽

Ermias Lulekal ◽

Awol Mekonnen ◽

...

Keyword(s):

Acute Toxicity ◽

Essential Oil ◽

Eucalyptus Globulus ◽

Biochemical Parameters ◽

Skin Irritation ◽

Toxicity Study ◽

Subacute Toxicity ◽

Acute Toxicity Study ◽

Limit Test ◽

Ointment Formulation

Background: The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats. Methods: The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects. Results: The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction. Discussion: In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application. Conclusion: This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.

Download Full-text

FORMULATION AND IN VITRO, IN VIVO EVALUATION OF PRONIOSOMAL GEL OF NEOMYCIN SULPHATE

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i2.30614 ◽

2019 ◽

pp. 156-163

Author(s):

AMOL SHETE ◽

PRIYANKA THORAT ◽

RAJENDRA DOIJAD ◽

SACHIN SAJANE

Keyword(s):

Phase Separation ◽

Skin Irritation ◽

Entrapment Efficiency ◽

Separation Method ◽

Gelling Agent ◽

In Vivo Evaluation ◽

Skin Delivery ◽

Span 60

Objective: The objectives of present investigation were to prepare and evaluate proniosomes of neomycin sulphate (NS) by coacervation phase separation method by using sorbitan monostearate (span 60) and lecithin as a surfactant to increase the penetration through the skin and study the effect of concentration of the same. Methods: Proniosomes of neomycin sulphate (NS) were prepared by coacervation phase separation method by using span 60 and lecithin. The effect of concentration of span 60 and lecithin was studied by factorial design. The prepared proniosomes were converted to gel by using carbopol as a gelling agent. The prepared formulations were evaluated for entrapment efficiency, in vitro drug diffusion, in vitro antibacterial activity and in vivo skin irritation test etc. Results: All Formulation showed the percentage entrapment efficiency in the range 38.31±0.05% to 77.96±0.06%, good homogeneity and gel was easily spreadable with minimal of shear. Optimized formulation showed enhanced rate of diffusion in vitro, increase in zone of inhibition against staphylococcus aureus, no skin irritation and showed good stability. Conclusion: The results of present study indicates that proniosomal gel formulated by using combination of span 60, Lecithin, cholesterol can be used to enhance skin delivery of NS because of excellent permeation of drug. Developed proniosomal gel formulation was promising carrier for NS

Download Full-text

Formulations Based on Drug Loaded Aptamer-Conjugated Liposomes as a Viable Strategy for the Topical Treatment of Basal Cell Carcinoma—In Vitro Tests

Pharmaceutics ◽

10.3390/pharmaceutics13060866 ◽

2021 ◽

Vol 13 (6) ◽

pp. 866

Author(s):

Anca N. Cadinoiu ◽

Delia M. Rata ◽

Leonard I. Atanase ◽

Cosmin T. Mihai ◽

Simona E. Bacaita ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Topical Treatment ◽

Skin Irritation ◽

In Vitro Tests ◽

Liposomal Drug ◽

Liposomal Formulations ◽

As1411 Aptamer

Topical liposomal drug formulations containing AS1411-aptamer conjugated liposomes were designed to deliver in a sustained way the 5-fluorouracil to the tumor site but also to increase the compliance of patients with basal cell carcinoma. The 5-fluorouracil penetrability efficiency through the Strat-M membrane and the skin irritation potential of the obtained topical liposomal formulations were evaluated in vitro and the Korsmeyer Peppas equation was considered as the most appropriate to model the drug release. Additionally, the efficiency of cytostatic activity for targeted antitumor therapy and the hemolytic capacity were performed in vitro. The obtained results showed that the optimal liposomal formulation is a crosslinked gel based on sodium alginate and hyaluronic acid containing AS1411-aptamer conjugated liposomes loaded with 5-fluorouracil, which appeared to have favorable biosafety effects and may be used as a new therapeutic approach for the topical treatment of basal cell carcinoma.

Download Full-text

Synthetic Nanoclay Gels Do Not Cause Skin Irritation in Healthy Human Volunteers

ACS Biomaterials Science & Engineering ◽

10.1021/acsbiomaterials.0c01615 ◽

2021 ◽

Author(s):

Luciana E. Bostan ◽

Claire E. Clarkin ◽

Mohamed Mousa ◽

Peter R. Worsley ◽

Daniel L. Bader ◽

...

Keyword(s):

Skin Irritation ◽

Healthy Human ◽

Human Volunteers

Download Full-text

Innovative approaches to avoid electric shaving-induced skin irritation

International Journal of Cosmetic Science ◽

10.1111/ics.12329 ◽

2016 ◽

Vol 38 ◽

pp. 10-16 ◽

Cited By ~ 1

Author(s):

M. Rietzler ◽

M. Maurer ◽

F. Siebenhaar ◽

S. Angelino ◽

J. Handt ◽

...

Keyword(s):

Skin Irritation ◽

Innovative Approaches

Download Full-text

Radiographic Outcomes, Union Rates, and Complications Associated With Plantar Implant Positioning for Midfoot Arthrodesis

Foot & Ankle Orthopaedics ◽

10.1177/24730114211027115 ◽

2021 ◽

Vol 6 (3) ◽

pp. 247301142110271

Author(s):

Tyler W. Fraser ◽

Daniel T. Miles ◽

Neal Huang ◽

Franklin B. Davis ◽

Burton D. Dunlap ◽

...

Keyword(s):

Hallux Valgus ◽

Skin Irritation ◽

Case Series ◽

Deformity Correction ◽

Valgus Deformity ◽

Union Rate ◽

Radiographic Outcomes ◽

Hallux Valgus Deformity ◽

Metatarsal Angle ◽

Radiographic Union

Background: Midfoot arthrodesis has long been successfully included in the treatment paradigm for a variety of pathologic foot conditions. A concern with midfoot arthrodesis is the rate of nonunion, which historically has been reported between 5% and 10%. Plantar plating has also been noted to be more biomechanically stable when compared to traditional dorsal plating in previous studies. Practical advantages of plantar plating include less dorsal skin irritation and the ability to correct flatfoot deformity from the same medial incision. The purpose of this study is to report the arthrodesis rate, the success of deformity correction, and the complications associated with plantar-based implant placement for arthrodesis of the medial column. Methods: A retrospective review was undertaken of all consecutive patients between 2012 and 2019 that underwent midfoot arthrodesis with plantar-positioned implants. Radiographic outcomes and complications are reported on 62 patients who underwent midfoot arthrodesis as part of a correction for hallux valgus deformity, flatfoot deformity, degenerative arthritis, Lisfranc injury, or Charcot neuroarthropathy correction. Results: Statistically significant improvement was seen in the lateral talus–first metatarsal angle (Meary angle) and medial arch sag angle for patients treated for flatfoot deformity correction. In patients treated for hallux valgus deformity, there was a reduction in the intermetatarsal angle from 15.4 to 6.8 degrees. The overall nonunion rate was 6.45% in all patients. The rate of nonunion was higher at the NC joint compared to the TMT joint and with compression claw plates. One symptomatic nonunion required revision surgery (1.7%). There were no nonunions when excluding neuroarthropathy patients and smokers. The odds ratio (OR) for nonunion in patients with neuroarthropathy was 6.05 ( P < .05), and in active smokers the OR was 2.33 ( P < .05). Conclusion: Plates placed on the plantar bone surface for midfoot arthrodesis achieved and maintained deformity correction with rare instances of symptomatic hardware for a variety of orthopedic conditions. An overall clinical and radiographic union rate of 94% was achieved. The radiographic union rate improved to 100% when excluding both neuroarthropathy patients and smokers. The incidence of nonunion was higher in smokers, neuroarthropathy patients, naviculocuneiform joint fusions, use of compression claw plates, and when attempting to fuse multiple joints. Incisional healing complications were rarely seen other than in active smokers. Level of Evidence: Level IV, case series.

Download Full-text