Non-pigmented laser hair removal mediated via sepia melanin nanoparticles: in vivo study on albino mice.

OBJECTIVES: Melanin is considered the main chromophore for laser hair removal. Due to a lack of laser-absorbing chromophores, removing non-pigmented hair with laser is quite problematic with unsatisfactory outcomes. This problem could be solved by delivering more melanin to the area around the hair follicle and enhancing that area as a target for light absorption. The insolubility of Sepia melanin as an exogenous dye, in most solvents, limits its bioavailability and thus its clinical use. METHODS: In our study, to overcome the solubility problems and increase the bioavailability of melanin for biomedical and cosmetic applications, natural sepia melanin was loaded in different nano-delivery systems (spanlastics and transfersomes) to be delivered to the hair follicles. The different formulations of melanin were prepared and characterized. In vivo skin deposition and histopathological studies were conducted on albino mice. RESULTS: Transmission electron microscopy (TEM) showed the spherical shape of the prepared vesicles with an average particle size of 252 and 262 nm and zeta potential of -22.5 and -35 mV for melanin spanlastics and melanin transfersomes, respectively. Histopathological examination of hair follicles and pilosebaceous glands for the irradiated and non-irradiated albino mice skin was studied post the application of the prepared formulations topically and subcutaneously. Qualitative statistical analysis was conducted and melanin transfersomes and melanin spanlastics showed significant damage to pilosebaceous glands and hair follicles with a p-value of 0.031 and 0.009 respectively. CONCLUSION: Melanin nanovesicles as transfersomes and spanlastics could be considered a promising approach for the removal of non-pigmented hair.

Novel Photodynamic/Photothermal Treatment of Fungal Keratitis Using Rose Bengal-Loaded Polypyrrole-Gold Nanoparticles in Wistar Albino Rats.

Purpose: Fungal keratitis is a potential corneal contagious disease mainly caused by yeast such as Candida albicans and filamentous fungi such as Aspergillus niger. The response of fungal keratitis to standard antifungals is limited by the poor bioavailability, the limited ocular penetration of antifungal drugs, and the development of microbial resistance. Photodynamic therapy using rose bengal (RB) as a photosensitizer was found to be effective in fungal keratitis management; however, the hydrophilicity of RB limits its corneal penetration. Polypyrrole-coated gold nanoparticles (AuPpy NP) were introduced as a nano-delivery system of RB with high loading capacity. It was proved that (RB-AuPpy NP) exhibited a combined photodynamic/photothermal effect. This study aims to use the combined photodynamic/photothermal effect of RB-AuPpy NP as a novel protocol for treating Fungal Keratitis in albino Wistar rats. Methods: The rats were infected by C. albicans and A. niger. Each infected group of rats was subdivided into groups treated by RB followed by radiation (photodynamic only), AuPpy NP followed by radiation (photothermal only), and RB-AuPpy NP followed by radiation (combined photodynamic/photothermal). Histopathological examination and slit lamp imaging were done to investigate the results. Results: The results revealed that 3 weeks post-treatment, the corneas treated by RB-AuPpy NP (combined photodynamic/photothermal effect) exhibited the best improvement compared to other groups. Conclusion: This protocol can be considered a promising one for Fungal Keratitis management that overcomes microbial resistance problems.

Gold-Polypyrrole-Loaded Eosin in Photo-Mediated Treatment of Hidradenitis Suppurativa: In Vivo Trans-Epidermal Permeation Study and Clinical Case Report.

This study reports a new protocol for the management of Hidradenitis Suppurativa (HS), depending on the synergistic photodynamic and photothermal effect of eosin yellow-gold-polypyrrole hybrid nanoparticles (E-G-Ppy NPs). E-G-Ppy NPs and gold-polypyrrole NPs (G-Ppy NPs) were synthesized, characterized, and formulated in topical hydrogels. Then, in vivo trans-epidermal permeation study, under both dark and white light-irradiation conditions, was done on albino mice. The E-G-Ppy hydrogel was then applied on a twenty-four years old female with recurrent axillary HS lesions pretreated with fractional CO2 laser. Thereafter, the treated lesions were irradiated sequentially, using an IPL system, in the visible (~550 nm) and NIR band (630-1100 nm) to activate the synthesized nanoparticles. Results showed that, upon application to mice skin, E-G-Ppy exhibited good tolerance and safety under dark conditions and induced degenerative changes into dermal layers after white-light activation, reflecting deep penetration. Photo-activation of E-G-Ppy hydrogel to a severe Hidradenitis Suppurativa case showed an improvement of 80% of the lesions according to average HS-LASI scores after 4 sessions with no recurrence during a follow-up period of six months. In summary, the dual photodynamic/photothermal activation of E-G-Ppy NPs can represent a promising modality for management of HS. Further expanded clinical studies may be needed.

Efficacy of the topical cyclosporine cream assisted by fractional carbon dioxide laser vs topical clobetasol cream for the treatment of plaque psoriasis: Randomized comparative study.

BACKGROUND: In mild psoriasis, topical agents remain the mainstay of treatment. However, the available treatments are not satisfactory for a significant proportion of patients in many terms such as efficacy and safety. Because of these deficits, augmentation of therapeutic effect seems desirable. THIS STUDY AIMS: To evaluate the efficacy of topical cyclosporine cream, delivered by fractional CO2 laser vs the efficacy of topical clobetasol cream for the treatment of mild to moderate plaque psoriasis. PATIENTS AND METHODS: Twenty-two patients with chronic plaque psoriasis involving <10% BSA were included in this study. They were randomly allocated into 2 groups. In Group A, patients were instructed to apply cyclosporine cream twice daily for 5 consecutive days per week immediately after fractional carbon dioxide laser session. While in Group B, clobetasol cream was applied twice daily for 5 consecutive days per week until complete clearance or for a maximum of 10 weeks. The efficacy was objectively assisted clinically and by histopathology by using the scores and skin biopsy. RESULTS: There was a significant improvement of erythema, plaque elevation, and scaling (p < 0.001) with the use of topical cyclosporine cream delivered by the aid of fractional CO2 laser, compared to base line. However, the improvement was more significant with topical clobetasol cream. CONCLUSION: Laser-assisted delivery of topical cyclosporine can provide comparable clinical and pathological improvement to that of clobetasol in the psoriatic plaques. These findings were apparent in patients with less widespread disease. However, topical steroid showed more improvement.

(Rose Bengal)/(Eosin Yellow)-Gold-Polypyrrole Hybrids: A Design for Dual Photo-Active Nano-System with Ultra-High Loading Capacity.

PURPOSE: Enhancement of the photodynamic/photothermal efficiency of two water-soluble dyes, rose bengal (RB) and eosin yellow (EY), via conjugation to a polymeric nano-system gold-polypyrrole nanoparticle (AuPpy NPs). METHODOLOGY: A multi-step synthesis method and an in situ one-pot synthesis method were used. Loading percentage, particle size, zeta potential, morphology, UV-Vis-NIR spectrophotometry and in vitro photothermal activity were measured. Then, both hybrid nanocomposites were examined for their cytotoxicity and photocytotoxicity on HepG2 cell line as a model for cancer cells. RESULTS: Dyes loaded in the traditional multi-step method did not exceed 9% w/w, while in the one-pot synthesis method they reached ~67% w/w and ~75% w/w for EY-AuPpy NPs and RB-AuPpy NPs, respectively. UV-Vis-NIR spectrophotometry showed that both nano-systems exhibited intense absorption in the NIR region. The mean size of the nanoparticles was ~31.5 nm (RB-AuPpy NPs) and ~33.6 nm (EY-AuPpy NPs) with zeta potential values of -26.5 mV and -33 mV, respectively. TEM imaging revealed the morphology of both hybrids, showing ultra-nano spherical-shaped gold cores in the case of RB-AuPpy NPs, and different shapes of larger gold cores in the case of EY-AuPpy NPs, both embedded in the polymer film. Conjugation to AuPpy was found to significantly reduce the dark cytotoxicity of both RB and EY, preserving the photocytotoxicity of EY and enhancing the photocytotoxicity of RB. CONCLUSION: Gold-polypyrrole nanoparticles represent an effective delivery system to improve the photodynamic and photothermal properties of RB and EY. The in situ one-pot synthesis method provided a means to greatly increase the loading capacity of AuPpy NPs. While both hybrid nanocomposites exhibited greatly diminished dark cytotoxicity, RB-AuPpy NPs showed significantly enhanced photocytotoxicity compared to the free dyes. This pattern enables the safe use of both dyes in high concentrations with sustained action, reducing dose frequency and side effects.

Novel greenly synthesized titanium dioxide nanoparticles compared to liposomes in drug delivery: in vivo investigation on Ehrlich solid tumor model.

AIMS: In a previous work, a pure crystalline titanium dioxide nanoparticles (TiO2NPs) were synthesized by green synthesis technique using Aloe vera leaves extract as reducing agent. In this work, we are aiming to investigate the potential of the novel greenly synthesized TiO2NPs as a nano-drug delivery system for the anticancer drug, doxorubicin (Dox). MAIN METHODS: The cytotoxicity of the synthesized TiO2NPs was tested on two cell lines; normal human skin fibroblasts (HSF) and breast adenocarcinoma cells (MCF-7). Then, Dox was loaded to both TiO2NPs (Dox- TiO2NPs) and liposomes (Dox-Lip). The loaded nanoparticles were characterized by TEM, FTIR, encapsulation efficiency, particle size and zeta potential measurement. Moreover, in vitro drug release was studied. Ehrlich tumor-bearing mice were used to study the anticancer activity of Dox- TiO2NPs, Dox-Lip, and aqueous Dox solution. Tumor volume, survival rate, and histopathological alterations were compared in all groups. KEY FINDINGS: Dox was successfully loaded to both liposomes and TiO2NPs with an encapsulation efficiency of 77% and 65%, respectively. The particle size of Dox-TiO2NPs, and Dox-Lip was 14.53 nm, and 103 nm, respectively. The cumulative Dox released from TiO2NPs and liposomes after 4 h was 18 and 46%, respectively.Dox-Lip and Dox-TiO2NPs resulted in the highest degree of tumor growth inhibition with 100% and 83% of treated animals remained alive, respectively. SIGNIFICANCE: The greenly synthesized TiO2NPs were proved to be as effective as liposomes in enhancing the anticancer activity of Dox.

Intralesional vitamin D3 versus new topical photodynamic therapy in recalcitrant palmoplanter warts Randomized comparative controlled study.

BACKGROUND: Recalcitrant palmoplanter warts represent a therapeutic challenge. Side effects of local destructive methods necessitates the need for other less morbid modalities. Recently immunotherapy as well as light based devices and lasers have emerged as therapeutic approaches. AIM OF THE STUDY: To compare between the safety and efficacy of intralesional vitamin D3 injection and photodynamic therapy (PDT) using eosin in treatment of recalcitrant palmoplanter warts. PATIENTS AND METHODS: Prospective, randomized, controlled comparative study. Fifty -six patients with recalcitrant palmoplanter warts were randomly divided into 3 groups. Group A was injected with intralesional vitamin D3. Group B was subjected to PDT using eosin loaded in trasferosomes as a photosensitizer. Group C is the control group. Clinical improvement was assessed by photographic records and dermoscopic assessment, at baseline, before each session and after completion of treatment. Patients were followed up for 6 months after cure to detect recurrence. RESULTS: Group A and B showed complete clearance in 88.89 % and 86.36 % respectively compared to 18.75 % in the control group. These results were statistically significant (P value<0.001). No side effects were reported except for pain during injection in group A. CONCLUSION: In the current study, both vitamin D3 and PDT using Eosin are safe, highly effective and well tolerated modalities in treatment of viral warts.

PEGylated lipid nanocarrier for enhancing photodynamic therapy of skin carcinoma using curcumin: in-vitro/in-vivo studies and histopathological examination.

The use of (PEG)-grafted materials has a positive impact on drug delivery. In this study we designed PEGylated lipid nanocarriers (PLN) loaded with curcumin (Cur) to target skin cancer by photodynamic therapy. Cur is a polyphenolic compound having vast biological effects masked due to its low aqueous solubility. PLN were prepared using Tefose 1500 with different surfactants. PLN3, containing Tween 80, had the smallest particle size (167.60 ± 15.12 nm), Z = - 26.91 mV and, attained the highest drug release (Q24 = 75.02 ± 4.61% and Q48 = 98.25 ± 6.89%). TEM showed spherical, well-separated nanoparticles. The dark and photo-cytotoxicity study on a human skin cancer cell line (A431) revealed that, at all tested concentrations, the viability of cells treated with PLN3 was significantly lower than those treated by Cur suspension and, it decreased upon irradiation by blue light (410 nm). The amount of Cur extracted from the skin of mice treated by PLN3 was twice that of mice treated by aqueous drug suspension, this was confirmed by the increase in fluorescence intensity measured by confocal laser microscopy. Histopathological studies showed that PLN3 could extend Cur effect to deeper skin layers, especially after irradiation. This study highlights the possible efficacy of curcumin-loaded PEGylated lipidic nanoparticles to combat skin cancer by photodynamic therapy.

Topical photodynamic therapy of tumor bearing mice with meso-tetrakis (N-methyl-4-pyridyl) porphyrin loaded in ethosomes.

Photodynamic therapy is a clinically approved procedure for the treatment of neoplastic and other non-malignant diseases. Meso-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP) is a photosensitizing agent which has been used in many applications. However, the use of TMPyP topically is limited due to its hydrophilicity. To overcome this problem, TMPyP was loaded in ethosomes. Three ethosomal formulae (A), (B) and (C) were prepared and characterized. Preparation (A) was chosen to be used in the in vitro and in vivo study, having the greatest encapsulation efficiency, the smallest size and the highest cumulative release percentage. The results of in vitro permeation study revealed that the ethosomal TMPyP was superior to the drug in the free form with permeation flux (3.92 µg cm-2 h-1). In the in vivo animal study done on Swiss albino mice, after 19 days of Ehrlich tumor implantation, the group treated with the ethosomal preparation showed significantly smaller tumor size (143.28 ±â€¯13.2 mm3) compared to the group treated with the free TMPyP (219 ±â€¯11.9 mm3). It showed also significant longer survival time (21 days) compared to that treated with the free drug (18.2 ±â€¯1.2 days). Based on the obtained results, transdermal delivery of TMPyP was potentiated by incorporating it in ethosomes.

Improved photodynamic efficacy of thiophenyl sulfonated zinc phthalocyanine loaded in lipid nano-carriers for hepatocellular carcinoma cancer cells.

BACKGROUND: The aim of the present study was to modify the structural activity of zinc(II)phthalocyanine by combining it with thiophenyl groups then loaded in lipid nano-carriers and evaluate its parameters required for the structure-activity relationship (SAR) for photodynamic therapy (PDT) of cancer. METHODS: Tetra (4-Thiophenyl) sulfonated phthalocyaninatozinc(II) (PhS·SO3Na)4ZnPc 5 was synthesized and characterized by various spectroscopic methods as a test compound. Liver hepatocellular carcinoma (HepG2) cells were treated with the synthesized (PhS·SO3Na)4ZnPc 5 derivative loaded in lipid nano carriers to understand the effect of combined compound on liver cancer cells. Furthermore, HepG2 cells were irradiated by visible red light at 60 mW/cm2 for 20 min. The phototoxicity of (PhS·SO3Na)4ZnPc 5 after being formulated in both (L) and transfersomes (T) was investigated. RESULTS: Overall, the results indicate that combination of thiophenyl groups substitution, in particular in the structure of sulfonated zinc phthalocyanine is able to improve the photodynamic properties of ZnPc, and (PhS·SO3Na)4ZnPc 5 loaded in lipid nano-carriers can be a promising combined PDT treatment strategy for Liver hepatocellular carcinoma (HepG2) cells. CONCLUSIONS: The new formulation ZnPc-lipid nano-carriers will be beneficial in the upcoming clinical trials and would enhance the inhibition of tumor growth.