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.

Response surface methodological approach for optimization of photodynamic therapy of onychomycosis using chlorin e6 loaded nail penetration enhancer vesicles.

Antimicrobial photodynamic inactivation (aPDI) has a tremendous potential as an alternative therapeutic modality to conventional antifungals in treatment of onychomycosis, yet the nail barrier properties and the deep-seated nature of fungi within the nails remain challenging. Therefore, the aim of this study was to prepare, optimize, and characterize Chorin e6 (Ce6) nail penetration enhancer containing vesicles (Ce6-nPEVs) and evaluate their photodynamic mediated effect against Trichophyton rubrum (T.rubrum); the main causative agent of onychomycosis. Optimization of the particle size and encapsulation efficiency of nPEVs was performed using a four-factor two-level full factorial design. The transungual delivery potential of the selected formulation was assessed in comparison with the free drug. The photodynamic treatment conditions for T.rubrum aPDI by free Ce6 was optimized using response surface methodology based on Box-Behnken design, and the aPDI effect of the selected Ce6-nPEVs was evaluated versus the free Ce6 at the optimized condition. Results showed that formulations exhibited high encapsulation efficiency for Ce6 ranging from 79.4 to 98%, particle sizes ranging from 225 to 859 nm, positive zeta potential values ranging from +30 to +70 mV, and viscosity ranging from 1.26 to 3.43 cP. The predominant parameters for maximizing the encapsulation efficiency and minimizing the particle size of Ce6-nPEVs were identified. The selected formulation showed 1.8-folds higher nail hydration and 2.3 folds improvement in percentage of Ce6 up-taken by nails compared to the free drug. Results of the microbiological study confirmed the reliability and adequacy of the Box-Behnken model, and delineated Ce6 concentration and incubation time as the significant model terms. Free Ce6 and Ce6-nPEVs showed an equipotent in vitro fungicidal effect on T.rubrum at the optimized conditions, however Ce6-nPEVs is expected to show a differential effect at the in vivo level where the advantage of the enhanced nail penetration feature will be demonstrated.

Transfersomal eosin topical delivery assisted by fractional CO2 laser for photodynamic treatment of palmar hyperhidrosis: case study.

Hyperhidrosis is a condition in which the cholinergic receptors on the eccrine glands are overstimulated, resulting in excessive sweating. It is considered a serious cosmetic and psychological problem that affects the patient's quality of life. Searching for novel treatment modalities is required to minimize the side effects and to attain better patient satisfaction.Photodynamic therapy (PDT), using eosin as a photosensitizer, is developed as a promising modality of the treatment of palmar and axillary hyperhidrosis. In this study, we treated six cases suffering palmar hyperhidrosis by applying the fractional CO2 laser prior to PDT session. For PDT, a hydrogel of eosin loaded in a transfersomes as a nano-delivery carrier was applied for 5 min, followed by irradiation by intense pulsed light (IPL). The prepared transfersomes loaded by eosin were spherical in shape with encapsulation efficiency of 33 ± 3.5%, particle size 305.5 ± 5.7 nm, average zeta potential of - 54 ± 7.6 mV with 80 ± 4% of the loaded eosin was released after 3 h. Two cases achieved 90% improvement after four sessions, three patients needed six sessions to show 75% improvement, while one patient showed only 25% improvement after six sessions. This resulted in shortening the time of PS application and decreasing the number of sessions required to achieve acceptable improvement. More clinical studies on large number of patients are required to optimize the results.

Photodynamic therapy fortified with topical oleyl alcohol-based transethosomal 8-methoxypsoralen for ameliorating vitiligo: Optimization and clinical study.

Vitiligo is a common autoimmune skin disorder that is characterized by patchy depigmentation of the skin due to melanocytes and melanin loss. Herein, photodynamic therapy mediated 8-methoxypsoralen (8-MOP), has been used fortified with topical oleyl alcohol-based transethosomes; to overcome the poor solubility and adverse effects associated with 8-MOP oral delivery. A 23 factorial design was used to study the formulation variables. In vitro and ex-vivo characterization besides a clinical study were conducted to assess therapeutic efficacy of the formulation. Results revealed that transethosomes were superior to transfersomes regarding drug protection from degradation. The optimized transethosomal formulation, composed of 50 mg oleyl alcohol, 10 mg Tween 80® and 20% v/v ethanol, exhibited high entrapment efficiency (83.87 ± 4.1%) and drug loading (105.0 ± 0.2%). Moreover, it showed small vesicular size (265.0 ± 2.9 nm) and PDI (0.19). The formulation depicted core and shell structure, high deformability index (12.45 ± 0.7 mL/s) and high ex-vivo skin permeation. The topical application of the developed 8-MOP transethosomal gel enhanced the effect of NB UVB radiation in the treatment of vitiligo patients and exhibited no side effects. Hence, it can be used as a future strategy for delivering 8-MOP without the need of systemic application.

(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.

Cationic zinc (II) phthalocyanine nanoemulsions for photodynamic inactivation of resistant bacterial strains.

BACKGROUND: The growing emergence of microbial resistance to antibiotics represents a worldwide challenge. Antimicrobial photodynamic inactivation (aPDI) has been introduced as an alternative technique, especially when combined with nanotechnology. Therefore, this study was designed to investigate the therapeutic merits of combined aPDI and nanoemulsion in infections caused by resistant bacterial strains. METHODS: Cationic zinc (II) phthalocyanine nanoemulsions (ZnPc-NE) were prepared using isopropyl myristate (IPM) as oil phase, egg phosphatidylcholine (egg PC) as emulsifier, and N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB). Nanoemulsions were characterized for particle size, polydispersity, zeta potential, viscosity, and skin deposition. The in-vitro aPDI was investigated on human resistant pathogens; gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative Multidrug-resistant strain of Escherichia coli (MDR E. coli), under different experimental conditions. In addition, in-vivo model of abrasion wound infected by MDR E. coli was induced in rats to investigate the therapeutic potential of the selected formulation. RESULTS: It was evident that the selected ZnPc formulation (20 % IPM, 2 % egg PC and 0.5 % CTAB) displayed a particle size of 209.9 nm, zeta potential +73.1 mV, and 23.66 % deposition of ZnPc in skin layers. Furthermore, the selected formulation combined with light achieved almost 100 % eradication of the two bacterial strains, with superior bacterial load reduction and wound healing propertiesin-vivo, compared to either the nanoemulsion formulation or laser alone. CONCLUSION: ZnPc nanoemulsion improved antimicrobial photodynamic therapy in inactivating resistant bacterial infections and provided a promising therapeutic means of treating serious infections, and hence could be applied in diseases caused by other bacterial strains.

Bergamot oil as an integral component of nanostructured lipid carriers and a photosensitizer for photodynamic treatment of vitiligo: Characterization and clinical experimentation.

Background: Bergamot oil (BO) is a photosensitizer that can be used for photodynamic therapy (PDT) of dermatological diseases such as vitiligo. Being an oil, it can be integrated within the lipidic matrix of nanostructured lipid carriers (NLCs) as the liquid lipid constituent, hence exhibiting a dual role. Research design and methods: NLCs were prepared with different emulsifiers and coemulsifiers, and the effect of the preparation method and formulation variables on the NLCs' size was elucidated. The prepared NLCs were further characterized for their in vitro release, viscosity, thermal behavior, and in vitro photostability. Furthermore, a preclinical photodynamic study on animal skin was conducted, followed by clinical experimentation on patients with vitiligo. Results: Results showed that BO was successfully incorporated within the NLCs. The selected NLCs formulation was in the nanometer range with a gel consistency, and it provided sustained release of BO for 24 h. NLCs improved the photostability and photodynamic properties of BO, and displayed promising preclinical and clinical results for the topical PDT of vitiligo. Expert Opinion: BO containing NLCs was proven to be promising means for PDT of vitiligo, and can be further explored in other dermatological diseases.

Contrasting the efficacy of pulsed dye laser and photodynamic methylene blue nanoemulgel therapy in treating acne vulgaris.

The treatment of acne remains a challenge for dermatologists. A variety of conventional therapies are available for acne treatment such as topical and systemic medications. Although many of these traditional acne treatments are effective, the wide-spread nature of the disease and its sometimes resistant nature delineate the need for alternative therapies. Therefore, over the past decade, phototherapy has been introduced for the treatment of acne, such as pulsed dye lasers (PDLs) and photodynamic therapy (PDT). The aim of this study was to compare the safety and efficacy of PDL and methylene blue-mediated photodynamic therapy (MB-PDT) in the treatment of mild to moderate acne. Split-face clinical trial including fifteen patients presenting with mild to moderate acne were treated with 585 nm PDL on the right side of the face and MB-PDT with 665-nm diode laser on the left side. The photosensitizer MB was prepared in nanoemulgel formulation, and the treatment was carried out for three sessions maximum at 2-weeks intervals. Results revealed that both PDL and MB-PDT were effective therapies in the treatment of acne, as manifested by the reduction of inflammatory and non-inflammatory lesions throughout the treatment period. However, the latter therapy was proven more potent in the reduction of acne severity, and in terms of patients' tolerance. Therefore, it can be concluded that MB in the nanoemulgel form is a promising treatment approach for acne, and can be further experimented in the treatment of other dermatological diseases.

Synthesis of Biocompatible and Environmentally Nanofibrous Mats Loaded with Moxifloxacin as a Model Drug for Biomedical Applications.

Biopolymeric chitosan structure (Cs) is rationally investigated owing to its potentiality in pharmaceutical applications. The synthetic routes of biomimetic Cs-based blend electrospun nanofibers were studied. Herein, biocompatible crosslinked electrospun polyvinyl alcohol (PVA)/Cs-reduced gold nanoparticles (Cs(Rg))/ß-CD (beta-cyclodextrin) in pure water were fabricated. To this end, supportive PVA as a carrier, Cs bio modifier, and gold reductant and ß-CD as smoother, inclusion guest molecule, and capping agent exhibit efficient entrapment of moxifloxacin (Mox) and consequently accelerate release. Besides, PVA/Cs(Rg)/ß-CD paves towards controlled drug encapsulation-release affinity, antimicrobial, and for wound dressing. Without losing the nanofiber structure, the webs prolonged stability for particle size and release content up to 96.4%. The synergistic effect of the nanoformulation PVA/Cs(Rg)/ß-CD against pathogenic bacteria, fungus, and yeast, including Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger, posed clear zones up to 53 φmm. Furthermore, a certain combination of PVA/Cs (Rg)/ß-CD showed a total antioxidant capacity of 311.10 ± 2.86 mg AAE/g sample. In vitro cytotoxicity assay of HePG2 and MCF-7 NF6 can eradicate 34.8 and 29.3 µg/mL against selected cells.

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.

One-Step Synthesis of Polypyrrole-Coated Gold Nanoparticles for Use as a Photothermally Active Nano-System.

OBJECTIVE: This paper introduces a simple one-step and ultra-fast method for synthesis of highly photothermally active polypyrrole-coated gold nanoparticles. The synthesis process is so simple that the reaction is very fast without the need for any additives or complicated steps. METHODOLOGY: Polypyrrole-coated gold nanoparticles (AuPpy NPs) were synthesized by reacting chloroauric acid (HAuCl4) with pyrrole (monomer) in aqueous medium at room temperature. These nanoparticles were characterized by UV-visible-NIR spectrometry, transmission electron microscopy (TEM), AC conductivity, zeta sizer and were evaluated for dark cytotoxicity and photocytotoxicity using human hepatocellular carcinoma (HepG2) cell line as a model for cancer cells. RESULTS: The synthesized AuPpy NPs showed a peak characteristic for gold nanoparticles (530-600 nm, molar ratio dependent) and a wide absorption band along the visible-NIR region with intensity about triple or even quadruple that of polypyrrole synthesized by the conventional FeCl3 method at the same concentration and under the same conditions. TEM imaging showed that the synthesized AuPpy NPs were composed of spherical or semi-spherical gold core(s) of about 4-10 nm coated with distinct layer(s) of polypyrrole seen either loosely or in clusters. Mean sizes of the synthesized nanoparticles range between ~25 and 220 nm (molar ratio dependent). Zeta potentials of the AuPpy NPs preparations indicate their good colloidal stability. AC conductivity values of AuPpy NPs highly surpass that of Ppy prepared by the conventional FeCl3 method. AuPpy NPs were non-toxic even at high concentrations (up to 1000 µM pyrrole monomer equivalent) under dark conditions. Unlikely, light activated the photothermal activity of AuPpy NPs in a dose-dependent manner. CONCLUSION: This method simply and successfully synthesized AuPpy NPs nanoparticles that represent a safe alternative photothermally active multifunctional tool instead of highly toxic and non-biodegradable gold nanorods.

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.

Nanovesicular Photodynamic Clinical Treatment of Resistant Plantar Warts.

BACKGROUND: Photodynamic therapy which involves the use of photosensitizer molecule activated by a light source was proven very promising for the treatment of dermatological diseases, especially the resistant ones such as recalcitrant Plantar Warts (PW). OBJECTIVE: However, its efficacy is hindered by the poor permeation of the photosensitizer molecule required to initiate skin photo-induced effects. METHODS: In this manuscript, the efficiency of the nano-vesicular system (transfersomes) as a potential topical drug delivery system for the photosensitizer methylene blue (MB) was investigated following clinical Photodynamic Therapy (PDT) in patients suffering from PW. RESULTS: Results revealed that MB transfersomal gel displayed a higher complete healing percentage for the lesions compared to the free MB gel (86.67% versus 53.57%) achieved at a lower number of treatment sessions (2.2 versus 4.14). Patients reported no signs of pain or inflammation, with no recurrence of the lesions during the follow up period of 8 months. CONCLUSION: PDT using transfersomal MB is an effective and safe therapeutic modality for the treatment of PW.

Curcumin-loaded nanostructured lipid carriers prepared using Peceol™ and olive oil in photodynamic therapy: development and application in breast cancer cell line.

PURPOSE: To potentiate the anticancer activity of curcumin (CUR) by improving its cell penetration potentials through formulating it into nanostructured lipid carriers (NLCs) and using the prepared NLCs in photodynamic therapy. METHODS: A 3×4 factorial design was used to obtain 12 CUR-NLCs using two factors on different levels: (1) the solid lipid type at four levels and (2) the solid to liquid lipid ratio at three levels. Olive oil, Tween 80 and lecithin were chosen as liquid lipid, surfactant and co-surfactant, respectively. CUR-NLCs prepared by high shear hot homogenization method were evaluated by determination of particle size (PS), polydispersity index, zeta potential (ZP), entrapment efficiency percent, drug loading percent and in vitro drug release. Optimization was based on the evaluation results using response surface modeling (RSM). Optimized formulae were tested for their in vitro release pattern and for dark and photo-cytotoxic anticancer activity on breast cancer cell line in comparison to free CUR. RESULTS: Evaluation tests showed the appropriateness of NLCs prepared from glyceryl monooleate and Geleol™ helped choosing two optimized formulae, PE3 and GE3. PE3 (prepared using glyceryl monooleate) showed enhanced release rates compared to GE3 (prepared from Geleol) and superior cytotoxic anticancer activity compared to both GE3 and free CUR under both light and dark conditions. The small mean PS, spherical shape as well as the negative ZP enhanced the internalization of the NLCs within cells. Modulation and inhibition of P-glycoprotein expression by glyceryl monooleate synergized the cytotoxic activity of CUR. CONCLUSION: CUR loading in NLCs enhanced its cell penetration and cytotoxic anticancer properties both in dark and in light conditions.

Novel bergamot oil nanospanlastics combined with PUVB therapy as a clinically translatable approach for vitiligo treatment.

The impact of nanomedicine has grown in the current decade; however, only very few clinical translational attempts have been realized. Therefore in the present study, we hypothesized that bergamot oil, a psoralen-containing oil, would produce an optimized melanogenic effect in the clinical treatment of vitiligo when loaded within an elastic nanocarrier (spanlastics) and combined with PUVB for activation of psoralens. Spanlastics were prepared and characterized for particle size, physical stability, in vitro release, thermal behavior, deformability, morphology, and in vitro photostability. The efficacy of the selected formula was tested histopathologically on rat skin and clinically translated in patients suffering from vitiligo. Results revealed that the spanlastics were of reasonable nanosize, deformable, and provided sustained release of bergamot oil. The incorporation of bergamot oil within spanlastics improved its photostability and its photodynamic activity. Spanlastics exhibited promising clinical results in terms of extent and onset of repigmentation in vitiligo patients. Therefore, it can be concluded that spanlastics can be introduced as a promising nanotreatment modality for vitiligo.

One-step synthesis of phyto-polymer coated gold nanospheres as a delivery system to enhance resveratrol cytotoxicity.

This study introduces a simple method for one-step synthesis of highly stable nontoxic polymer-coated gold nanospheres for use in drug delivery, focuses on the ability of chloroauric acid (HAu Cl4 ) to induce polyphenols polymerization, puts up an easy procedure for loading hydrophobic drugs onto gold nanoparticles with ultra-high loading efficiency and studies the cytotoxicity of free and gold nanoparticles-loaded resveratrol. Gold nanospheres were synthesized simply by direct reaction between resveratrol itself and HAu Cl4 in aqueous medium. Synthesized gold nanospheres exhibited high stability in both aqueous and ethanolic solutions. UV-visible spectrum showed that the synthesized gold nanospheres have maximum absorption at 532 nm. TEM imaging, mass and FT-IR spectrometry revealed the presence of a distinct polymeric shell around each nanoparticle. Resveratrol, as a chemopreventive agent, was loaded onto the synthesized gold nanospheres with an ultra-high loading capacity (11.6% w/w). Free resveratrol, free gold nanospheres, and resveratrol-loaded gold nanospheres were examined for cytotoxicity on HepG2 cell line where cytotoxicity of loaded resveratrol was dramatically enhanced to reach about nine folds as that of free resveratrol at the same concentration.

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

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.