Maha Fadel

New topical photodynamic therapy for treatment of hidradenitis suppurativa using methylene blue niosomal gel: a single-blind, randomized, comparative study.

Hidradenitis suppurativa (HS), is a chronic, recurrent dermatosis affecting skin that contains apocrine glands. Photodynamic therapy using aminolaevulinic acid (ALA) activated by intense pulsed light (IPL) have shown variable success rates, with some adverse effects.

Topical colloidal indocyanine green-mediated photodynamic therapy for treatment of basal cell carcinoma

Abstract Indocyanine green (ICG) is a near-IR fluorescent dye with a great potential for application as photosensitizer in topical photodynamic therapy (PDT) of skin diseases. Despite its merits, its use has been hampered by its high degradation rate. Therefore, in the current article, ICG was encapsulated in a vesicular colloidal nanocarrier (transfersomes), with the aim of enhancing its therapeutic efficacy. Transfersomes were characterized for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release and histopathological effect on mice skin. A pilot clinical study was conducted to test its therapeutic potential for PDT of basal cell carcinoma (BCC). Transfersomal ICG displayed particle size (∼125 nm) and a negative zeta potential (∼−31 mV). Transfersomes were also able to sustain the release of ICG >2 h. Upon incorporation of transfersomal ICG in gel form, it was found to maintain the normal histology of mice skin post-irradiation with diode laser 820 nm. Moreover, ICG transfersomal PDT achieved 80% clearance rate for BCC patients with minimal pain reported during treatment. The previous findings suggest that transfersomal nanoencapsulated ICG is a promising treatment modality for BCC.

Evaluation of hypericin-loaded solid lipid nanoparticles: Physicochemical properties, photostability and phototoxicity

Hypericin (HYP), a natural photosensitizer, has powerful photo-oxidizing ability, tumor-seeking characteristics, and minimal dark toxicity; nevertheless, it has proven high lipid solubility compared to its sparingly water soluble nature. Therefore, its formulation into solid lipid nanoparticles (SLNs) has attracted increasing attention as a potential drug-delivery carrier. Two HYP-loaded SLNs formulations were prepared utilizing microemulsion-based technique. Thereafter, the physicochemical properties of the formulations were investigated and evaluated. HYP-loaded SLNs showed spherical shape with mean particle size ranging from 200–300 nm for both formulations (FA and FB). The encapsulation efficiencies reached above 80% and FA showed significant higher encapsulation than FB (P < 0.05), also, the thermal analysis using differential scanning calorimetry (DSC) indicated good compatibility between hypericin and lipids forming the cores in both formulations. Spectroscopic measurements of the photostability study showed that hypericin encapsulation into SLNs improved its photostability, compared to free HYP in 0.1% ethanolic solution. However, photocytotoxicity studies on HepG2 cells revealed an evident inhibition of the photodynamic efficacy of HYP-loaded SLNs, compared to free HYP. In conclusion, although the elevated entrapment efficiency of HYP into SLNs increased its photostability, it decreased its phototoxicity which might be due to the quenching deactivation of HYP molecules resulting from SLN compactness and thickness structure.

Jojoba oil soft colloidal nanocarrier of a synthetic retinoid: preparation, characterization and clinical efficacy in psoriatic patients.

BACKGROUND Nanotechnology has provided substantial benefits in drug delivery, especially in the treatment of dermatological diseases. Psoriasis is a chronic inflammatory skin disease in which topical delivery of antipsoriatic agents is considered the first line treatment. OBJECTIVE To investigate whether the encapsulation of the synthetic retinoid tazarotene in a nanocarrier based on jojoba oil would decrease its irritation potential and clinically improve its therapeutic outcome in psoriatic patients. METHOD A microemulsion system based on jojoba wax and labrasol/plurol isostearique was prepared and characterized. RESULTS The selected formula displayed spherical morphology, particle size of 15.49±2.41 nm, polydispersity index of 0.20 ±0.08, negative charge and low viscosity. The microemulsion provided two folds increase in skin deposition of tazarotene, correlating with higher reduction in psoriatic patients PASI scores after treatment (68% reduction in PASI scores versus 8.96% reduction with the marketed gel). No irritation was encountered in patients using microemulsion, with redness and inflammation reported with the marketed gel-treated patients. CONCLUSION Jojoba oil microemulsion proved to be advantageous in reducing the irritancy of tazarotene, enhancing its skin deposition and achieving better therapeutic outcome in psoriatic patients.

Photodynamic efficacy of hypericin targeted by two delivery techniques to hepatocellular carcinoma cells

The photocytotoxic effect of hypericin (Hyp) targeted by two different delivery techniques, namely, liposomes and anti-hepatocyte specific antigen (anti-HSA) was investigated. Optical absorption and steady-state fluorescence were used to analyze the conjugation of Hyp with anti-HSA model and to evaluate the encapsulation capacity and drug release in a liposome model. Particle size and thermal analysis of the prepared liposomes were performed using laser-light scattering and differential scanning calorimetry (DSC), respectively. Viability study of HepG2 cells exposed to Hyp in the two delivery systems, in the dark and following visible light irradiation, was performed in comparison to free Hyp. The intracellular uptake and localization of Hyp in HepG2 cells were analyzed by means of spectrofluorometry and fluorescence microscopy. Spectroscopic measurements demonstrated that Hyp binds to anti-HSA in its monomeric form. The photocytotoxic effect of Hyp depended clearly on the form of Hyp administered, either in free form, loaded into liposomes or conjugated with anti-HSA. While liposomes loaded with Hyp (Lip-Hyp) did not induce significant phototoxicity, both free Hyp or anti-HSA-Hyp inflicted substantial cell mortality, after photoirradiation. The intracellular uptake of Lip-Hyp by HepG2 cells was estimated to be 20% less compared to free Hyp or anti-HSA-Hyp. In spite of the equal uptake of both free Hyp and anti-HSA-Hyp, HepG2 cells demonstrated a relatively higher mortality with anti-HSA-Hyp compared to free Hyp.

Novel methotrexate soft nanocarrier/fractional erbium YAG laser combination for clinical treatment of plaque psoriasis

Abstract Psoriasis is a commonly encountered chronic dermatological disease, presenting with inflammatory symptoms in patients. Systemic treatment of psoriasis is associated with several adverse effects, therefore the development of a customized topical treatment modality for psoriasis would be an interesting alternative to systemic delivery. The therapeutic modality explored in this article was the comparative treatment of psoriatic patients using nanoparticulated methotrexate in the form of jojoba oil-based microemulsion with or without fractional erbium YAG laser. Assessment parameters included follow-up photography for up to 8 weeks of treatment, estimation of the psoriasis severity [TES (thickness, erythema, scales)] score, and histopathological skin evaluation. The prepared methotrexate microemulsion was clinically beneficial and safe in treatment of psoriasis vulgaris. The concomitant use of the fractional laser provided improvement in the psoriatic plaques within shorter time duration (3 weeks compared to 8 weeks of treatment), presenting an alternative topical treatment modality for psoriasis vulgaris.

Photodynamic diagnosis of parathyroid glands with nano-stealth aminolevulinic acid liposomes

Background The use of ALA to identify the parathyroid glands had been investigated both experimentally and clinically with promising results but the side effects from the systemic use of this photosensitizer reduce its widespread in clinical use. The aim of this study is to test the formulation of ALA in nano-stealth liposomes for better photodiagnosis of parathyroid glands intraoperatively with less ALA dose. MATERIALS AND METHODS Preparation of ALA nanovesicles and in vitro characterization for the drug encapsulation percentage, vesicle size and Zeta potential then the study of nanovesicles stability and in vitro drug release profile was done. The study compared nano-stealth liposomes and nano-liposomes with the free ALA solution, intraperitoneal administration of these different ALA formulations in rats and observing the ability to identify parathyroids intraoperatively and evaluation of fluorescence differences between these groups. RESULTS AND CONCLUSION Stealth liposomes were insignificantly higher in drug encapsulation%, in vitro drug release and zeta potential compared to conventional liposomes. Additionally, they needed less time for the start of the photosensitization and recorded the highest signal after spectrometry compared to the other two preparations. These data provide a new evidence of the potentiality of ALA-stealth Liposomes for identification of PTGs intraoperatively and could lead to propose a non-invasive procedure with reduced postoperative side effects.

Comparative enhancement of curcumin cytotoxic photodynamic activity by nanoliposomes and gold nanoparticles with pharmacological appraisal in HepG2 cancer cells and Erlich solid tumor model

Abstract Curcumin is a natural pigment that generates singlet oxygen upon light excitation, hence it can be used as a photosensitizer in photodynamic therapy. The extremely low water solubility and poor systemic bioavailability make curcumin a challenging molecule to be used clinically. In this study, two nanocarrier systems for curcumin were prepared and characterized; nanoliposomes and polyvinyl pyrrolidone-capped gold nanoparticles. The dark and photocytotoxicity were investigated as a function of light fluence rate (100 and 200 mW/cm2) on HepG2 cancer cells. In vivo Erlich tumor model was developed and comparison of the tumor volume, survival rate, and histopathological alterations was made for the two nanocarriers. Results showed that both curcumin nanocarriers were successfully prepared and characterized. Light irradiation was able to augment the cytotoxicity of both curcumin liposomes and gold nanoparticles, with the former being superior in cytotoxicity compared to the latter. The tumor size was almost diminished 1 month post-photodynamic treatment for both systems with regression in the number of tumor cells upon histopathological evaluation, with curcumin liposomes producing better tumor regression than gold nanoparticles with comparable survival rate. Liposomes were confirmed to be superior to gold nanoparticles as a photodynamic treatment modality for cancer.

A randomized, controlled, double-blind study evaluating photodynamic white hair removal using topical liposomal Rose Bengal

One of the challenges of OMICS research is the integration of new data into the preexisting, and then re-interpretation of the integrated data. We used readily available meta-analysis computational methods to integrate new data on the transcriptomic effects of EGF in primary human epidermal keratinocytes with the preexisting transcriptomics data in keratinocytes. We separately addressed the consequences of adding EGF to keratinocyte cultures and its reverse, blocking the EGFR kinase with Tyrphostin AG1478. We first starved primary human epidermal keratinocytes for 24 hrs and next treated them with EGF. Then, we compared the genes expressed in the treated and control cultures in parallel, using Affymetrix microarrays. We find that the addition of EGF promotes keratinocyte proliferation, attachment and motility and, surprisingly, induces DUSPs, the phosphatases that attenuate the EGF signal. Using metaanalysis, we identified overlapping effects of EGF with those of IL-1 and IFNg, both activators of keratinocyte in wound healing and inflammation. We also identified and characterized the genes and pathways which are suppressed by EGF but are induced by agents promoting epidermal differentiation, such as Ephrins and JNK inhibitors. EGFR activation is important in many malignancies, including cutaneous SCC, lung, colon and other cancers, and targeting the EGFR is currently used to treat such cancers. However, a significant drawback to EGFR targeted therapies is the skin toxicity side effect. This toxicity usually presents as hair and nails abnormalities, papular or pustular folliculitis and pruritic dry skin. These limit the usefulness of EGFR targeting therapies. Surprisingly, the transcriptional effects of EGFR inhibition have not been extensively explored in epidermal keratinocytes. Therefore, we treated primary human epidermal keratinocytes with Tyrphostin AG1478, a specific inhibitor of the EGFR kinase, and compared the treated and control cultures using Affymetrix microarrays. The observed changes were integrated with the preexisting data on transcriptional profiling in epidermal keratinocytes. We find that the inhibition of EGFR suppresses the transcription of genes linked to keratinocyte proliferation, attachment and motility. Interestingly, inhibiting EGFR promotes apoptosis by both induction of proapoptotic and suppression of antiapoptotic genes. Certain transcriptional effects of EGFR inhibition counter the transcriptional effects of retinoids. Surprisingly, EGFR inhibition strongly and specifically induces expression of markers of epidermal differentiation. Overall, our work defines the yin-yang of EGF signaling in human epidermis, namely both the changes responding to activation of the EGF receptor, and its inhibition. Moreover, this work can serve as a paradigm for integration and analysis of new omics data with the large bodies of data in public repositories.Nowadays facial wasting is considered a stigma of HIV-infection; well-known are the devastant effects on facial features of the drugs used for the higly active anti-retroviral therapy. Years after years, several techniques and filling devices have been proposed to restore facial features of these patients. Several authors stated that when facial wasting is associated with trunk lipohypertrophy (another side effect related to the drugs intake), structural fat graft is the best option achievable, because at the same time, removing the lipohypertrophied fat of the body, and using it to fill the face, let to reach a great improvement both at the face and the body. However, often and often, the injected fat can be resorbed in a very high percentage, so the use of dermal filler is quite frequent to help the physicians in treating these patients in removing facial wasting’s stigma. Several fillers have been proposed for this purpose, however, HIV-infected patients presenting facial wasting are not like cosmetic patients seeking a little improvement, these patients need a treatment more reconstructive than cosmetic; this is why long lasting or permanent fillers are often used, and in these cases the physician need different skills. Furthermore, it is very important how these fillers act once injected, and if late side effects can be seen; so, only long follow-up let a physician, involved in this tretament, to really understand what works and what doesn’t. The author presents what he learned by its own experince, in using fillers for facial wasting rehabilitation.M has been used to treat inflammatory skin conditions; however, there is limited data with regard to pharmacokinetic, dosage adjustment, and clinical response. The methotrexate polyglutamate (MTX PG3) assay was developed as a marker to measure methotrexate activity in vivo in determining the optimal therapeutic range in patient management. Our objective was to evaluate the methotrexate polyglutamte assay in assessing whether the measurable methotrexate metabolite correlates with a clinical response in pediatrics patients with inflammatory skin diseases treated with methotrexate. A retrospective chart review was performed on 47 children from SSM Cardinal Glennon Children’s Medical Center with a median age of 8 years (range, 2-17 years) and mean treatment duration of 363.42 days over a 24 month period. MTX PG3 levels were recorded from the MTX PG3 assay. Clinical treatment was evaluated using a Physician Global Assessment scale (0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe) re-classified into 0=poor/fair and 1=good/excellent. Patients were categorized into responders, defined as patients changing from poor/fair to good/excellent, and non-responders, defined as patients remaining at poor/fair. Late-responders, defined as children responding after 12 months, were compared with non-responders using mean maximum and mean percent change in MTX PG3 levels. Data analyzed using statistical t-tests. Of the 47 patients, stratified into two groups: responders 38/47 (81%) and non-responders 9/47 (19%). Responders and non-responders had a mean MTX PG3 level of 31.5 and 22.3, respectively, p=0.138. Late-responders and non-responders had a mean change of 42.6% and 19.1% and mean maximum of 41.9 and 22.3 MTX PG3 levels, respectively, p=0.01. This study has been limit primarily by a small sample size. MTX PG3 levels do not correlate with clinical response between responders and non-responders. However, amongst late and non-responders, MTX PG3 assay remains a viable test in adjusting dosage in association with clinical response. In the end, MTXPG3 levels are more predictive for late than early responders.Laser hair removal of blond and white hair is acomplicated task with often unsatisfactory results as a result of lack of laser-absorbing chromophore. In the present study, we investigated if repetitive sessions of photodynamic therapy (PDT) using Topicall application of liposomal rose bengal (RB) hydrogel followed by intense pulsed light (IPL) exposure enables removal of white and gray hair. Liposomal RB in hydrogel was prepared and pharmaceutically characterized. Fifteen adult females, skin phenotypes III–IV were entered into the study. They were determined to have white terminal hair. Unwanted facial hair was treated for three sessions at 4–6 week intervals using intense pulsed light (IPL). At each treatment: the treatment area was pre-treated with topical liposomal rose RB gel. While a control group of another 15 patients applied Placebo gel before IPL treatment. Hair regrowth was measured 4 weeks after each treatment and additionally 6months after the last treatment by counting the number of terminal hair compared with baseline pretreatment values. Rate of hair regrowth, complications and treatment outcomes were documented. Mean regrowth in the liposomal RB group was 63%after 3 treatment cycles. Six months after therapy, average terminal hair count compared with baseline pretreatment showed 40% reduction, and no recorded side effects. Also significant difference was seen compared with the control group, the clinical outcome was promising. As a conclusions photodynamic therapy using liposomal RB hydrogel in combination with IPL treatment showed significant efficacy in the treatment of white hair compared with a control group.