Development of gallic acid loaded composite nanovesicles for the topical treatment of acne: optimization, characterization, and clinical investigation.

Gallic acid (GA) proved to produce desired effects topically in the treatment of acne, through its antibacterial, anti-inflammatory and antioxidant characteristics. In the current work, nanovesicular systems; aspasomes loaded with GA were prepared, and evaluated on in-vitro and ex-vivo levels. Formulations were coated with chitosan due to its mucoadhesive properties. Results indicated that the size of the formulations ranged between 273.20 and 855.00 nm, with positively charged zeta potential ranging between 30.60 and 34.40 mV, EE% ranging between 57.651% and 95.20% and good stability after 3-months storage. The formulae provided a sustained drug release of 98.22% over 24 h, 5.4-fold higher ex-vivo skin deposition compared to GA solution, and powerful antioxidant potential compared to the control solution and appeared as spherical bilayer vesicles on being examined using transmission electron microscope. A clinical study was carried out on patients suffering from acne, where the reduction percent of comedones, inflammatory, total acne lesions and infiltrate was calculated. Results revealed that aspasomes exhibited reduction percentages of 72.35%, 80.33%, 77.95% and 90.01% ± for comedones, inflammatory lesions, total lesions, and infiltrate, respectively compared to control solution providing an effective topical delivery system for the management of acne.

Nano-vesicular systems for melanocytes targeting and melasma treatment: In-vitro characterization, ex-vivo skin retention, and preliminary clinical appraisal.

Melasma represents an acquired melanogenesis disorder resulting in skin's hyperpigmentation effect. Although several approaches are adopted for melasma treatment, nanotechnology presents the most convenient one. Therefore, the present work aimed to formulate and characterize three nano-vesicular systems namely, liposomes, penetration enhancer containing vesicles (PEVs) and invasomes to enhance the topical delivery of the skin whitening agent; alpha arbutin (α-arbutin) for the treatment of melasma. Liposomes were prepared according to a 23 full factorial design and the selected formula was further employed for the preparation of PEVs and invasomes. Results showed that the three vesicular systems exhibited nano-sizes ranging from 151.95 to 672.5 nm, negative charges ranging from -12.50 to -28.20 mV, high entrapment efficiencies ranging from 80.59 to 99.53 %, good stability and prolonged-release of α-arbutin for 24 h after dispersion in hydrogel form. The deposition study from the vesicular hydrogel confirmed their effectiveness for the drug's accumulation in the skin reaching an average of 1.6-fold higher in the stratum corneum, 1.6-1.8-fold higher in the epidermis, and 1.6-1.8-fold higher in the dermis compared to the free drug dispersion in hydrogel. A preliminary clinical split-face study on patients suffering from melasma revealed that α-arbutin-loaded liposomes and PEVs in hydrogel forms showed better clinical outcomes compared to the free α-arbutin hydrogel as well as to the previously published α-arbutin encapsulated in chitosan nanoparticles and dispersed in hydrogel form. This delineates the aforementioned nano-vesicular systems as effective and clinically superior delivery means for melasma management.

Novel anti-psoriatic nanostructured lipid carriers for the cutaneous delivery of luteolin: A comprehensive in-vitro and in-vivo evaluation.

Psoriasis is a prevalent laborious inflammation in skin with alternate phases of remission and relapses. The current study sought to develop nanostructured lipid carriers (NLCs) having enhanced skin deposition as well as augmented anti-inflammatory potential, to repurpose the use of luteolin (Lut), a flavonoid, in the treatment of psoriasis. NLCs were prepared using different oils having reported anti-inflammatory activity and evaluated in terms of size, surface charge, entrapment efficiency, stability upon storage, in-vitro anti-inflammatory potential, surface morphology, in-vitro release profile and release kinetics, and ex-vivo skin deposition. In-vivo animal studies were conducted on the optimized formula using imiquimod-induced psoriasis rat model. The prepared NLCs were nanosized ranging from 202 to 538 nm, negatively charged with values having the range of -13.10 to -19.26 mV with high entrapment efficiency values ranging from 84.21 to 96.53% and high in-vitro anti-inflammatory potential compared to the blank and control formulations. Furthermore, NLCs demonstrated adequate storage stability demonstrated by slightly significant change in their colloidal properties. The prepared nanoparticles exhibited sustained drug release up to 24 h and succeeded in enhancing the skin deposition of Lut by 3.4-fold higher in stratum corneum, epidermis and dermis compared to Lut suspension with minimum transdermal delivery. In-vivo assessment of psoriasis was carried out morphologically, histopathologically and biochemically and results revealed significant augmentation of the anti-psoriatic efficacy of Lut upon its encapsulation in NLCs compared to free Lut suspension. The developed system proved to be an influential drug delivery system providing potent anti-psoriatic therapy, paving the way for futuristic clinical investigations.

Functionalized chitosan nanoparticles for cutaneous delivery of a skin whitening agent: an approach to clinically augment the therapeutic efficacy for melasma treatment.

The increase in the production of melanin level inside the skin prompts a patient-inconvenient skin color disorder namely; melasma. This arouses the need to develop efficacious treatment modalities, among which are topical nano-delivery systems. This study aimed to formulate functionalized chitosan nanoparticles (CSNPs) in gel form for enhanced topical delivery of alpha-arbutin as a skin whitening agent to treat melasma. Ionic gelation method was employed to prepare α-arbutin-CSNPs utilizing a 24 full factorial design followed by In vitro, Ex vivo and clinical evaluation of the nano-dispersions and their gel forms. Results revealed that the obtained CSNPs were in the nanometer range with positive zeta potential, high entrapment efficiency, good stability characteristics and exhibited sustained release of α-arbutin over 24 h. Ex vivo deposition of CSNPs proved their superiority in accumulating the drug in deep skin layers with no transdermal delivery. DSC and FTIR studies revealed the successful amorphization of α-arbutin into the nanoparticulate system with no interaction between the drug and the carrier system. The comparative split-face clinical study revealed that α-arbutin loaded CSNPs hydrogels showed better therapeutic efficacy compared to the free drug hydrogel in melasma patients, as displayed by the decrease in: modified melasma area and severity index (mMASI) scores, epidermal melanin particle size surface area (MPSA) and the number of epidermal monoclonal mouse anti-melanoma antigen recognized by T cells-1 (MART-1) positive cells which proved that the aforementioned system is a promising modality for melasma treatment.

Clinical cosmeceutical repurposing of melatonin in androgenic alopecia using nanostructured lipid carriers prepared with antioxidant oils.

BACKGROUND: The present work aims to formulate nanostructured lipid carriers (NLCs) exhibiting high skin deposition and high inherent antioxidant potential to repurpose the use of melatonin hormone and some antioxidant oils in the treatment of androgenic alopecia (AGA). RESEARCH DESIGN AND METHODS: NLCs were characterized for their size, charge, drug entrapment, anti-oxidant potential, physical stability, in vitro release, surface morphology, and ex-vivo skin deposition. Their merits were clinically tested on patients suffering from AGA by calculating the degree of improvement, conduction of hair pull test, histometric assessment, and dermoscopic evaluation. RESULTS: Results revealed that melatonin NLCs showed nanometer size, negatively charged surface, high entrapment efficiency, and high anti-oxidant potential, in addition to sustained release for 6 h. Furthermore, NLCs displayed good storage stability and they were able to increase the skin deposition of melatonin 4.5-folds in stratum corneum, 7-folds in epidermis, and 6.8-folds in the dermis compared to melatonin solution. Melatonin NLCs displayed more clinically desirable results compared to the melatonin solution in AGA patients, manifested by increased hair density and thickness and decreased hair loss. CONCLUSIONS: The aforementioned system was shown to be a very promising treatment modality for AGA, which is worthy of futuristic experimentation.

Melatonin vitamin C-based nanovesicles for treatment of androgenic alopecia: Design, characterization and clinical appraisal.

The present study aimed to develop vitamin C based nanovesicles (aspasomes) loaded with the antioxidant melatonin, as a novel cosmeceutical to be used for clinical treatment of androgenic alopecia (AGA). Aspasomes were assessed regarding their particle size, charge, drug entrapment, anti-oxidant potential, physical stability, in vitro release, surface morphology, and ex-vivo skin deposition. Clinically, melatonin aspasomes were tested on AGA patients, and assessed by evaluating the degree of improvement through conduction of hair pull test, histometric analysis and dermoscopic evaluation. Results revealed that melatonin aspasomes showed favorable pharmaceutical properties in addition to clinically promising results compared to melatonin solution, manifested by increased hair thickness, density and decreased hair loss, with photographic improvement in most patients. Therefore, melatonin vitamin C-based aspasomes were clinically auspicious in the treatment of AGA, hence, paving the way for their further exploration in other oxidative-dependent dermatological diseases.

Recent Advances in Antioxidant Cosmeceutical Topical Delivery.

Antioxidants are among the most important cosmeceuticals, with proven ability of inhibiting cellular damage. The topical skin administration of antioxidants is essential for minimizing skin aging and achieving better skin protection against harmful free radicals. However, their unfavorable physiochemical properties such as chemical instability, excessive hydrophilicity or lipophilicity and others could be a great obstacle against their skin promising effects as well as their delivery to deeper skin layers. These problems could all be remedied through the use of delivery carriers. The present review discusses the various delivery carriers which were proven successful in improving the beneficial effects of antioxidants against skin aging, namely different vesicular systems, lipidic systems, polymeric systems and carbon nanotubes, and their applications in topical antioxidant delivery.