Investigating the potential of Quercetin enthused nano lipoidal system for the management of dermatitis

Objective: The present research work was undertaken to develop quercetin enthused nanolipoidal systems and its characterization. The objective was to investigate potential of prepared system in the management of DNCB induced dermatitis. Method: Nanolipoidal system was prepared in different combinations with quercetin, L-α phosphatidylcholine (SPC) and ethanol and characterized for particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency, percentage drug release, skin retention and skin permeation. Selected batches were further incorporated into Carbopol 934 base gel. The vesicles were in size range 324.19-359 nm while polydispersity index (PDI) ranges from 0.241-0.554 and for zeta potential, it was from -26.33 to -39.3 nm. Entrapment efficiency was from 23.77-94.68 %. Confocal laser scanning microscopy showed penetration depth of rhodamine enthused ethosome across rat skin up to 45.23 µm which was significantly higher than the rhodamine solution (10 µm). In dinitrochlorobenzene (DNCB) induced mice dermatitis model histopathology study showed a marked decrease in amount of inflammatory cell nucleus in mice treated with quercetin loaded ethosomal gel followed by 76.13% decrease in-ear swelling and ear mass respectively in morphology study. The conventional marketed formulation showed a nominal decrease in epidermal thickness. Further Primary irritation index was less than 0.4 indicating negligible irritation in all the groups. Results: The optimized formulation F6 with SPC and ethanol in the ratio of 20:80 displayed the highest drug content and entrapment efficiency of 94.68±1.14%. PDI was 0.241±0.11 and skin retention 7.7%. Batch F6 with vesicle size and zeta potential of 324.9±19 nm and -26.33 mV, respectively, was incorporated in Carbopol 934 base gel and the prepared gel was evaluated for morphology, spreadability, in vitro, ex vivo release study, and kinetics study and in vivo studies. Conclusion: The present study revealed that the developed ethosomal gel can be used for enhanced delivery of Quercetin via skin. The in vitro studies indicated that the gel serves as an efficient carrier for Quercetin. It showed its effectiveness in the management of dermatitis. Further, Quercetin loaded nanoethosomal gel formulation can be viewed as a promising drug delivery system for the management of dermatitis.

New Strategies for Improving Budesonide Skin Retention

The aim of this work was to evaluate the ex vivo effect of the combination of two strategies, complexation with cyclodextrin, and poloxamer hydrogels, for improving water solubility in the dermal absorption of budesonide. Two hydrogels containing 20% poloxamer 407, alone or in combination with poloxamer 403, were prepared. Each formulation was loaded with 0.05% budesonide, using either pure budesonide or its inclusion complex with hydroxypropyl-β-cyclodextrin, and applied in finite dose conditions on porcine skin. The obtained results showed that for all formulations, budesonide accumulated preferentially in the epidermis compared to the dermis. The quantity of budesonide recovered in the receptor compartment was, in all cases, lower than the LOQ of the analytical method, suggesting the absence of possible systemic absorption. The use of a binary poloxamer mixture reduced skin retention, in line with the lower release from the vehicle. When the hydrogels were formulated with the inclusion complex, an increase in budesonide skin retention was observed with both hydrogels. Poloxamer hydrogel proved to be a suitable vehicle for cutaneous administration of budesonide.

Formulation Consideration and Skin Retention-Permeation Study of Insitu Nanogel Containing Dimethylfumarate for Treatment of Psoriasis

Aims and Objective: to develop and evaluate an insitu nanogel formulation containing dimethylfumarate for targeted topical delivery therapy of psoriasis. Study Design: 32 full factorial design Place and Duration of Study: Department of Pharmaceutics, Parul Institute of Pharmacy and Research, Parul University, Vadodara, between 2016 to 2019. Methodology: Nanogel were formulated by chemical cross linked gel method using Polyvinyl alcohol and Hyaluronic acid (1:5) ratio using Glutaraldehyde (GA) (25 %w/v) and Hydrochloric acid (HCl) (6%v/v) as a crosslinking agent and catalyst. Dimethylfumarate loaded nanogel were clear and showed physicochemical parameters desired for topical delivery and stability. Results: The Permeation profile of dimethylfumarate through rat skin from selected nanogel formulation exhibited highest skin uptake. The Micoscopic observations indicated that the optimized nanogel had n significant effect on the microscopic structure of the sin and epithelial cells appered mostly unchanged. The surface epithelium lining and the granular cellular structure of the skin were totally intact. The developed Nanogel may be a potential drug delivery vehicle for targeted topical delivery of dimethylfumarate in the treatment of psoriasis. Conclusion: As per drug retention study the highest amount of drug retained on the skin and lowest amount of drug permeate to the skin. Hence it was observed that there was no significant correlation between skin retention and skin permeation study.

Improvement of Imiquimod Solubilization and Skin Retention via TPGS Micelles: Exploiting the Co-Solubilizing Effect of Oleic Acid

Imiquimod (IMQ) is an immunostimulant drug approved for the topical treatment of actinic keratosis, external genital-perianal warts as well as superficial basal cell carcinoma that is used off-label for the treatment of different forms of skin cancers, including some malignant melanocytic proliferations such as lentigo maligna, atypical nevi and other in situ melanoma-related diseases. Imiquimod skin delivery has proven to be a real challenge due to its very low water-solubility and reduced skin penetration capacity. The aim of the work was to improve the drug solubility and skin retention using micelles of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of vitamin E, co-encapsulating various lipophilic compounds with the potential ability to improve imiquimod affinity for the micellar core, and thus its loading into the nanocarrier. The formulations were characterized in terms of particle size, zeta potential and stability over time and micelles performance on the skin was evaluated through the quantification of imiquimod retention in the skin layers and the visualization of a micelle-loaded fluorescent dye by two-photon microscopy. The results showed that imiquimod solubility strictly depends on the nature and concentration of the co-encapsulated compounds. The micellar formulation based on TPGS and oleic acid was identified as the most interesting in terms of both drug solubility (which was increased from few µg/mL to 1154.01 ± 112.78 µg/mL) and micellar stability (which was evaluated up to 6 months from micelles preparation). The delivery efficiency after the application of this formulation alone or incorporated in hydrogels showed to be 42- and 25-folds higher than the one of the commercial creams.

Nanosystems in Cosmetic Products: A Brief Overview of Functional, Market, Regulatory and Safety Concerns

Nanosystems exhibit various innovative physico-chemical properties as well as a range of cosmetic functions, including increased skin retention for loaded compounds. The worldwide nano-market has therefore been consistently extensive in recent decades. This review summarizes the most important properties of nanosystems that are employed in cosmetics, including composition, functions and interactions with skin, with particular attention being paid to marketed products. Moreover, the worldwide regulatory landscape of nanomaterials used as cosmetic ingredients is considered, and the main safety concerns are indicated. In general, advanced physico-chemical characterization is preliminarily needed to assess the safety of nanomaterials for human health and the environment. However, there is currently a shortfall in global legislation as a universally accepted and unambiguous definition of a nanomaterial is still lacking. Therefore, each country follows its own regulations. Anyhow, the main safety concerns arise from the European context, which is the most restrictive. Accordingly, the poor dermal permeation of nanomaterials generally limits their potential toxic effects, which should be mainly ascribed to unwanted or accidental exposure routes.

The Effect of Cream and Gel Vehicles on the Percutaneous Absorption and Skin Retention of a New Eugenol Derivative With Antioxidant Activity

The effect of cream and gel vehicles containing clove water on skin permeability was compared for a new eugenol derivative (eugenyl dichloroacetate—EDChA) with antioxidant activity. In vitro permeation experiments were conducted in a Franz cell with porcine skin. The cumulative mass and skin accumulation of EDChA were investigated and compared. The antioxidative capacity of the studied vehicles was determined by using the diphenylpicrylhydrazyl (DPPH) free radical reduction method. The antioxidant activity (evaluated with DPPH, ABTS, and the Folin–Ciocalteu methods) of the fluid that penetrated through the pig skin and of the fluid obtained after the skin extraction, were also determined. For comparison, eugenol was also tested. The results of this work could contribute to the development of vehicles with antioxidant potential estimated after 24 h of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin. The waste water from the clove buds steam distillation -contains several valuable biologically active compounds, and its use is environmentally friendly. We observed that gel vehicles were the best enhancer of skin permeation for both eugenol and its derivative. In most cases, -similar cumulative masses of eugenol and its ester were found in the acceptor fluid. The accumulation of EDChA was higher for cream vehicles in relation to the parent eugenol when applied onto the skin. The greatest amounts of eugenol were accumulated in the skin when these compounds were used in gel vehicles.

Chitosomes-In-Chitosan Hydrogel for Acute Skin Injuries: Prevention and Infection Control

Burns and other skin injuries are growing concerns as well as challenges in an era of antimicrobial resistance. Novel treatment options to improve the prevention and eradication of infectious skin biofilm-producing pathogens, while enhancing wound healing, are urgently needed for the timely treatment of infection-prone injuries. Treatment of acute skin injuries requires tailoring of formulation to assure both proper skin retention and the appropriate release of incorporated antimicrobials. The challenge remains to formulate antimicrobials with low water solubility, which often requires carriers as the primary vehicle, followed by a secondary skin-friendly vehicle. We focused on widely used chlorhexidine formulated in the chitosan-infused nanocarriers, chitosomes, incorporated into chitosan hydrogel for improved treatment of skin injuries. To prove our hypothesis, lipid nanocarriers and chitosan-comprising nanocarriers (≈250 nm) with membrane-active antimicrobial chlorhexidine were optimized and incorporated into chitosan hydrogel. The biological and antibacterial effects of both vesicles and a vesicles-in-hydrogel system were evaluated. The chitosomes-in-chitosan hydrogel formulation demonstrated promising physical properties and were proven safe. Additionally, the chitosan-based systems, both chitosomes and chitosan hydrogel, showed an improved antimicrobial effect against S. aureus and S. epidermidis compared to the formulations without chitosan. The novel formulation could serve as a foundation for infection prevention and bacterial eradication in acute wounds.

Design and Evaluation of Dissolving Microneedles for Enhanced Dermal Delivery of Propranolol Hydrochloride

Oral propranolol hydrochloride has been the first-line treatment for infantile hemangioma (IH), whereas systemic exposure to propranolol has the potential of causing serious adverse reactions. Dermal delivery of propranolol is preferable due to high local drug concentration and fewer adverse effects. However, propranolol hydrochloride (BCS class I) is highly hydrophilic and has difficulty in penetrating the stratum corneum (SC) barrier. Dissolving microneedles (MNs) are an efficient tool for overcoming the barrier of the SC and enhancing dermal drug delivery. In this study, propranolol hydrochloride-loaded dissolving MNs were fabricated by using hyaluronic acid and polyvinyl pyrrolidone as matrix materials. Controllable drug loading in needle tips was achieved by a two-step casting procedure. The needles were good in mechanical strength for penetrating the SC while presented excellent dissolving capability for releasing propranolol hydrochloride. In comparison with the solution counterpart, irrespective of being applied to intact skin or solid MNs-pretreated skin, dissolving MNs significantly increased the permeability and skin retention of propranolol. In conclusion, dissolving MNs could be a potential approach for enhancing dermal delivery of propranolol to treat IH.