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Hyperpigmentation is darkened patches or spots on the skin occurred by increased melanin. Undecylenoyl phenylalanine (Sepiwhite®), as a commercial lipophilic derivative of phenylalanine, is a powerful new brightener that can be used in the treatment of skin pigmentation disorders.Solid lipid nanoparticles (SLNs) increase the efficiency of hydrophobic drugs. The current study aimed to prepare and characterize SLNs containing Sepiwhite (SEPI-SLN).In this study, an optimized SEPI-SLN formulation was selected by applying the response surface method. In vitro drug loading content, the release profile of SEPI, and cell viability were investigated. The permeation rate of SEPI-SLN was also compared to conventional cream containing Sepiwhite (SEPI-CREAM). Furthermore, the anti-tyrosinase activity of Sepiwhite was also evaluated.The optimized formulation showed a spherical morphology with particle size and entrapment efficiency of 218.6 ± 11.1 nm and % 87.31 ± 0.65, respectively. Differential scanning calorimetry (DSC) analysis confirmed SEPI-loaded SLN formulation with no drug-lipid incompatibility. The in vitro permeation experiment revealed the enhanced cutaneous uptake of SEPI-SLN. The results also showed that Sepiwhite could stop melanogenesis with inhibition of the tyrosinase enzyme.Our findings confirm that SLNs could be a proper nanocarrier for the relevant usage of Sepiwhite as a powerful brightener agent.

Sepiwhite is a novel anti-pigmenting agent that is derived from fatty acid and phenylalanine and used for hyperpigmentation induced by light exposure or inflammation. In this study, a simple and validated high-performance liquid chromatography method for the quantitation of sepiwhite was developed. Optimized forced degradation of sepiwhite at thermal, acid/base, photolysis, oxidative, and heavy metal ions conditions were evaluated and the effect of each of them on production of specific 10%-30% degradants was studied by the approach of design of experiments. Sepiwhite accelerated study was conducted and toxicity of sepiwhite at each condition was tested. An optimized high-performance liquid chromatography method was validated by a face-centered central composition design. Ten different degradants were identified from sepiwhite and degradation behavior under different conditions was studied. Sepiwhite and its degradant products show no cytotoxicity. This optimized high-performance liquid chromatography method can be applied for quality control assay and sepiwhite degradation behavior may be considered in the manufacturing of sepiwhite products.

This study was performed to explore the physicochemical and anti-biofilm properties of rifampin (Rif) and cis-2-decenoic acid (C2DA) co-entrapped in solid lipid nanoparticles, Rif-C2DA-SLN, against staphylococcal biofilm. The formulation was prepared by high-shear homogenization and ultrasound methods and characterized for size, zeta potentials, encapsulation efficacy, drug lipid interaction studies (DSC), shape morphology (TEM), stability studies, and in vitro anti-biofilm activity against Staphylococcus aureus and S. epidermidis biofilm. The zeta potentials, particle sizes, and encapsulation efficacy of final formulations were 19.0 ± 7.64 mV, 127.2 ± 2.8 nm, and approximately 69% (Rif) and 46% (C2DA), respectively. SLN formulations were stable for 12 months. DSC studies showed no chemical interaction between drugs and lipids. SLN formulations showed better in vitro anti-biofilm activity than free forms especially in the stage of biofilm formation. Nanoparticles were not able to remove the formed biofilm. Simultaneous entrapment of Rif and C2DA by SLN is reported for the first time, and Rif-C2DA-SLN can be applied as an efficient nanoparticulate system with potential anti-biofilm activities. These data suggest that the combined strategies for delivery of both C2DA and Rif by nanoparticulate systems would pave the way toward developing the strategies to combat biofilms.

Solid lipid nanoparticles (SLN) loaded by Ziziphora clinopodioides Lam. were synthesized using the method of high shear homogenization and ultra sound. The lipid phase consisted of percirol ATO5 and campritol 888 (5% w/v). Poloxamer 188 (2.5% w/v) was used as surfactant. Different amount of essential oil (1, 2, 2.5% w/v) were added to SLN. Particle size of solid lipid nanoparticle loaded by essential oil (2.5%) (SLN-EO) was 241.1 nm with poly dispersity index (PDI) of 0.312 and Zeta potential – 22.6 mv. Entrapment efficiency of SLN-EO (2.5%) was 93%. Transmission electron microscopy (TEM) study showed the spherical particles with the size under 100 nm. Based on the results of fumigant toxicity, the LC50 values of SLN-EO and pure oil against Tribolium castaneum were 30.602 and 68.303 µL. L air−1, respectively. These results demonstrated that SLN-EO had higher toxicity effects on red flour beetles. The comparative assessment of persistence indicated SLN-EO formulation remained effective until 14 days, while the pure oil lost its toxicity after the 8th day of application. Chemical composition of Ziziphoraclinopodioides showed that pulegone (51.78%), 1, 8- cineole (8.95%), p- menthone (7.74%) and piperitenone (5.7%) were the major components.

Purpose: The aim of this study was to characterize the undecylenoyl phenylalanine (Sepiwhite (SEPI))-loaded nanostructured lipid carriers (NLCs) as a new antimelanogenesis compound. Methods: In this study, an optimized SEPI-NLC formulation was prepared and characterized for particle size, zeta potential, stability, and encapsulation efficiency. Then, in vitro drug loading capacity and the release profile of SEPI, and its cytotoxicity were investigated. The ex vivo skin permeation and the anti-tyrosinase activity of SEPI-NLCs were also evaluated. Results: The optimized SEPI-NLC formulation showed the size of 180.1±5.01 nm, a spherical morphology under TEM, entrapment efficiency of 90.81±3.75%, and stability for 9 months at room temperature. The differential scanning calorimetry (DSC) analysis exhibited an amorphous state of SEPI in NLCs. In addition, the release study demonstrated that SEPI-NLCs had a biphasic release outline with an initial burst release compared to SEPI-EMULSION. About 65% of SEPI was released from SEPI-NLC within 72 h, while in SEPI-EMULSION, this value was 23%. The ex vivo permeation profiles revealed that the higher SEPI accumulation in the skin following application of SEPI-NLC (up to 88.8%) compared to SEPI-EMULSION (65%) and SEPI-ETHANOL (74.8%) formulations (P

Noscapine is a benzylisoquinoline alkaloid isolated from poppy extract, used as an antitussive since the 1950s, and has no addictive or euphoric effects. Various studies have shown that noscapine has excellent anti-inflammatory effects and potentiates the antioxidant defences by inhibiting nitric oxide (NO) metabolites and reactive oxygen species (ROS) levels and increasing total glutathione (GSH). Furthermore, noscapine has indicated antiangiogenic and antimetastatic effects. Noscapine induces apoptosis in many cancerous cell types and provides favourable antitumour activities and inhibitory cell proliferation in solid tumours, even drug-resistant strains, via mitochondrial pathways. Moreover, this compound attenuates the dynamic properties of microtubules and arrests the cell cycle in the G2/M phase. Noscapine can reduce endothelial cell migration in the brain by inhibiting endothelial cell activator interleukin 8 (IL-8). In fact, this study aimed to elaborate on the possible mechanisms of noscapine against different disorders.

Vitamin D is an essential vitamin for bone marrow development and immune function, which is mostly synthesized in the skin through sun exposure. The high global prevalence of vitamin D deficiency requires a feasible approach to administer vitamin D to a larger number of population in a shorter amount of time, and this may be achieved through food fortification. Food fortification using nanostructured lipid carriers (NLC) and nanoemulsions appears to be an ideal method to enhance bioavailability, stability, and solubility of bioactive compounds. The aim of this study was to develop NLC and nanoemulsion forms of vitamin D to evaluate its efficacy for further enrichment of dairy products. NLC containing Precirol and nanoemulsion containing vegetable oils were prepared and characterized for polydispersity index, particle size, zeta potential, particle shape, crystal properties, stability, encapsulation efficiency, and releasing. Vitamin D3 NLC size was in the range of 123.4 to 210.6 nm and for nanoemulsion 137.6 to 171.6 nm, respectively. Optimal NLC and nanoemulsion carriers were selected for morphological assessment, encapsulation efficiency, thermal analysis, and release study. Scanning and transmission electron microscopy revealed that particles had approximately spherical shape. In gastric simulated solution (pH = 1.2), NLC and nanoemulsion form of vitamin D3 released 9.3% and 26.9% of vitaminD3, respectively. This indicated that our formulation is able to protect vitamin D3 under acidic conditions. The results of this study revealed that NLC and nanoemulsion could be an optimal carrier for food fortification in order to improve bioavailability of bioactive compounds such as vitamin D.

Objective(s): The present study aimed to determine and compare moisturizing and occlusion effects of different solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using magnetized water and deionized water. Materials and Methods: SLN formulations were prepared using various lipids, including Tripalmitin, Compritol®, Precirol®, and emulsifiers including Poloxamer and Tween 80. NLC formulations were also prepared with oleic acid and the same solid lipids. Two types of formulations were prepared; first with deionized water and then with magnetized water. Formulations were prepared using high shear homogenization and ultrasound methods. The products were analyzed by PSA (particle size analyzer), DSC (differential scanning calorimetry), and TEM (transmission electron microscopy). The moisturizing effect of formulations was determined by in vivo and in vitro methods. Results: Findings of the assessments demonstrated that in products prepared with magnetized water, 5% SLN Precirol® had the most moisturizing effect in vivo and 5% SLN Compritol® had the most moisturizing effect in vitro. The use of magnetized water in formulations can improve the effectiveness and increase the stability of moisturizing products. Conclusion: In this study, all products prepared with magnetized water showed more stability, smaller size, and more moisturizing effects compared with products prepared with deionized water.

Liposomal formulations were made using Solvent-assisted active loading technology (SALT). Two formulations composed of HSPC:DPPG:Chol:DSPE-mPEG2000 (PG-LipCUR) and HSPC:Chol:DSPE-mPEG2000 (LipCUR) demonstrated good colloidal properties and the CUR-encapsulation of 82% and 89% for PG-LipCUR and LipCUR, respectively. The results showed that both formulations were stable during 6 months storage at 4 °C. The release study showed that the PG-LipCUR and LipCUR formulations are relatively stable at pH 7.4. Both formulations had higher cytotoxicity on TUBO and 4T1 cell lines in compassion with normal cells. PG-LipCUR had the higher amounts of CUR cellular uptake than LipCUR. Biodistribution studies showed that both formulations could enhance the half-life of the CUR 2–3 times compared to free CUR. The tumor accumulation of PG-LipCUR was significantly higher than LipCUR. The antitumor activities of liposomes on 4T1 tumor model demonstrated the efficacy of both formulations compared to PBS and free CUR. PG-LipCUR also was more potent in tumor growth delay in comparison with LipCUR. However, combination of the Caelyx® and PG-LipCUR had the most antitumor properties among other treatments. Based on the results, PG-LipCUR could be a promising formulation for the delivery of CUR which also significantly increased the efficacy of Caelyx® and merits further investigation.

In this study, the effect of natural macromolecules as carrier agents on the biological activity of nano-encapsulated Bene hull polyphenols (Pistacia atlantica subsp. Mutica) through W/O/W emulsions was evaluated. The W/O microemulsions as primary emulsions and a complex of soy protein isolate and basil seed gum (SPI-BSG), whey protein isolate and basil seed gum (WPI-BSG) and also Hi-Cap 100 in the outer aqueous phase were used to produce W/O/W nano-emulsions. Z-average size of emulsions stabilized by Hi-Cap, WPI-BSG, and SPI-BSG was 318, 736.9 and 1918 nm, respectively. The encapsulation efficiency of polyphenols for powders produced by Hi-Cap, WPI-BSG, and SPI-BSG was 95.25, 90.9 and 92.88%, respectively, which was decreased to 72.47, 67.12 and 64.44% after 6 weeks storage at 30 °C. The antioxidant activity of encapsulated polyphenols at 100, 200 and 300 ppm was measured in oil by peroxide and p-anisidine values during storage and was compared to non-encapsulated extract and synthetic antioxidant. Results showed oxidative alterations in oils containing encapsulated polyphenols was lower than unencapsulated form, which among them capsules produced by SPI-BSG exhibited higher antioxidant effects due to the better gradual release. Generally, the higher antioxidant potential was achieved with increased solubility and controlled release of polyphenols through their nano-encapsulation.

In this study, solid lipid nanoparticles containing Eugenia caryophyllata essential oil (SLN-EO) were prepared by high-shear homogenization and ultrasound methods, and used to eradicate pathogens. SLN formulations were evaluated for their size, zeta potential and encapsulation efficacy (EE). The morphological and thermal properties of the formulations were analysed by transmission electron microscopy (TEM) and differential scanning calorimetry methods. The lead formulations were chosen and tested with minimum inhibitory concentration (MIC), MBC and time-kill methods to investigate the antimicrobial activity against Salmonella typhi, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. The particle size of three final formulations were 397 ± 10·1, 786·9 ± 11 and 506·4 ± 22 nm respectively. The zeta potential of all formulations was negative values. The size of the formulations was slightly increased during 3 months storage at 25°C. The TEM imaging showed that formulation had spherical shape. The EE of EO was estimated approximately 70%. MIC and MCC values of SLN-EO were lower than those of the oil alone. The time-kill studies showed that SLN-EO was either equivalent to or better than EO (P-value

Auraptene (AUR) is a bioactive antioxidant coumarin with valuable pharmacological properties; however, poor water solubility is a substantial issue for the topical application of AUR. Therefore, we sought to prepare solid lipid nanoparticles (SLNs) containing AUR (AUR-SLNs) to enhance its anti-inflammatory effect. The prepared formulations were optimized by applying the response surface method. Furthermore, AUR-SLNs were compared to conventional cream containing AUR regarding both the permeation rate of the nanoparticles and the anti-inflammatory effect through both in vitro and in vivo studies. Particle size and entrapment efficiency of the optimized formulation were 140.9 ± 3.55 nm and 84.11% ± 3.30, respectively. Transmission electron microscopy revealed that the nanoparticles were spherical. Differential scanning calorimetry (DSC) analysis demonstrated no drug-lipid incompatibility in the formulation. Fourier transform-infrared spectroscopy (FTIR) spectra revealed the amorphous state of AUR and the encapsulation of this agent in SLNs. The in vitro permeation studies exhibited that AUR-SLNs could significantly enhance cutaneous uptake of AUR and skin targeting. The anti-inflammatory and histopathological studies exhibited no significant differences between AUR-SLNs and indomethacin. AUR-SLNs did not induce skin sensitization in guinea pigs. The results suggest that SLNs could be appropriate carriers for the topical application of AUR as a natural anti-inflammatory agent.

The diffusion coefficients of mass transfer in colloidosomes are sensitive to environmental changes. Also, Fick’s law of diffusion cannot be solved analytically in presence more complex geometries or non-constant active agent diffusivities. Because of the approximation property and uncertainty handing of fuzzy systems, here they are employed to model diffusion coefficients in the caffeine release from hydrogel colloidosomes. The approximated diffusion coefficients are then used in the Fick’s law equations, to create the fuzzy-diffusional model. The identification and validation of the fuzzy-diffusion model is obtained from experimental caffeine release curves of colloidosome samples in different shear rates, and at two time ranges. The proposed method is then compared with three other methods and depicts lower error and variance both in identification and evaluation. The diffusional-fuzzy model maintains the interpretability of the Fick’s model, improves the process simulation and eliminates phenomenon and property considerations.

The aim of this study was to prepare, characterize and evaluate solid lipid nanoparticles and nanostructured lipid carriers containing phycocyanin from Spirulina platensis. These nanocarriers were prepared through ultrasound-assisted high-shear homogenization method. The results showed that the type and amount of lipid and surfactant had a significant effect on the particle size distribution, polydispersity index and zeta potential. The results of differential scanning calorimetry, fourier transorm infrared spectroscopy and X-ray diffraction analyses indicated no phycocyanin peak in the prepared formulations, showing the effectiveness of nanocarriers systems in phycocyanin encapsulation. The results of the investigations on particles morphology showed that the produced nanoparticles were spherical and uniform and their size ranged from 50 to 80 nm. The nanoparticle encapsulation efficiency varied from 37 to 69%.

The aim of this study was to prepare and characterize a new nanocarrier for oral delivery of tamoxifen citrate (TMC) as a lipophilic oral administrated drug. This drug has low oral bioavailability due to its low aqueous solubility. To enhance the solubility of this drug, the microemulsion system was applied in form of oil-in-water. Sesame oil and Tween 80 were used as drug solvent oil and surfactant, respectively. Two different formulations were prepared for this purpose. The first formulation contained edible glycerin as co-surfactant and the second formulation contained Span 80 as a mixed surfactant. The results of characterization showed that the mean droplet size of drug-free samples was in the range of 16.64-64.62nm with a PDI value of

Curcuminoids are considered as one of the most promising phytochemicals with numerous pharmacological effects and therapeutic potentials. Nevertheless, their inappropriate pharmacokinetic properties (i.e., poor bioavailability) have made pharmaceutical industries face many challenges in developing an efficient formulation. To address this issue, we designed curcuminoids-loaded solid lipid nanoparticles (CUR-SLNs) and nanostructured lipid carriers (CUR-NLCs) using high shear homogenization and ultrasound technique. The optimized SLNs and NLCs formulations exhibited average particle sizes of 160.7 ± 2.69 and 151.4 ± 3.54 nm, respectively. The encapsulation efficiency of CUR-SLNs and CUR-NLCs were 95.30% ± 1.71 and 97.37% ± 2.83. Transmission electron microscopy imaging revealed the spherical shape of the lipid nanoparticles. Differential scanning calorimetry (DSC) studies showed an amorphous state of the curcuminoids incorporated into the nanoparticles. Furthermore, pharmacokinetic studies that were conducted to prove the absorption enhancing effect of the developed formulations, demonstrated significant improvement in pharmacokinetic parameters including area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax) of the nanocarriers in comparison with free curcuminoids. The results suggested that SLNs and nanomicellar formulations, as compared to NLCs, were better functioned at boosting the pharmacokinetic properties of curcuminoids.

We have investigated the co-addition of hexadecylphosphocholine (HePC) and a Tat derived peptide (Tat), coupled to Maleimide-PEG2000-DSPE pegylated liposomal doxorubicin (PLD) in many respects, including drug and liposome cellular delivery, drug release, biodistribution, in vivo cell delivery and antitumor activity. The liposomes were HePC-free and -containing liposomes, from which liposomes with 25, 50, 100 and 200 numbers of Tat/liposome were prepared. Similarly, DiI-C18 (3)-model liposomes (DiI-L and DiI-HePC-L) were prepared. HePC and Tat increased cellular delivery of Dox and cytotoxicity in B16F0 melanoma and C26 colon carcinoma cells. Tat enhanced liposome-cell interaction and caused Dox burst release. HePC and Tat reduced the serum retention time of liposomal Dox, slightly and dramatically, respectively. In comparison, Tat-liposomes enhanced Dox delivery to liver and spleen cells 3h post-injection. Likewise, Dox content of these tissues and tumor was lower at 24h. The naïve liposomes retarded tumor growth more effectively and their related median survival time of the treated C26 bearing BALB/c mice was longer than those of Tat-liposomes (MST45days versus MST38days). Overall liposomes exhibiting sustained drug release and negligible cell interaction were more suitable delivery systems in targeting cancerous tumors and suppressing their growth.

Objective The aim of the present study was to assess the in vitro anti-biofilm activities of solid lipid nanoparticles (SLN) loaded with rifampin against biofilm-producing Staphylococcus epidermidis . Methods SLN were prepared and characterized for size, zeta potentials and encapsulation efficacy. The morphological and thermal properties of formulation were evaluated by TEM imagining and DSC analysis. The anti-biofilm activity of different formulations was assessed at different incubation times and concentrations by crystal violet (CV) and viable biofilm count methods. Results The zeta potentials, particle sizes and encapsulation efficiencies of final formulations were 17 ± 0.7 mV, 101 ± 4.7 nm and approximately 70%; respectively. Rifampin-SLN was able to reduce the biomass of biofilm at time- and concentration-dependent manner. According to biofilm count results, the Rifampin-SLN was more effective for removal of the bacteria with respect to free rifampin. Conclusion The results of this study highlight the advantages and efficiency of Rifampin-SLN in biofilm eradication.

7-ethyl-10-hydroxy camptothecin (SN38) is poorly soluble in water and pharmaceutical solvents. Oral administration of SN38 was restricted due to poor solubility. Many ways such as encapsulation in carriers are used for solving this restriction. Solid lipid nanoparticles (SLNs) are able to encapsulate lipophilic drugs and improve oral bioavailability. In addition, concomitant use of the efflux pump inhibitors can improve the performance of the encapsulated drug. In the present study, SN38 was loaded in SLNs. Nanoparticle size, zeta potential and drug encapsulation efficacy were investigated. The drug release from nanoparticles was also determined in the simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). Cytotoxicity of nanoparticles after 24 and 48 h were measured in C26 and Caco-2 cell lines. The cellular uptake of the drug was determined. Tumor growth inhibition and survival were evaluated in animal model. The results showed that the drug-loaded SLNs were about 172.3 ± 3.3 nm in size. The encapsulation efficacy was 61% ± 7. In cellular studies, higher toxicity of the drug-loaded nanoparticles with the two substances piperine and quercetin were achieved in the Caco-2 cell line. It was observed that drug uptake of nanoparticles containing SN38 with or without piperine and quercetin by C26 and Caco-2 cell line was significantly higher than free SN38 in 2 and 4 h. According to in vivo studies, the use of piperine and quercetin with SLN containing SN38 has produced a favorable synergistic effect as increasing the survival time in animal model.

The aim of this study was to prepare a microemulsion based hydrogel containing sesame oil and evaluate its topical application in preventing the harmful effects of UV radiation on the guinea pig's skin using histopathologic and clinical findings. Sesame oil with high antioxidant content and unique chemical and physiological properties is a suitable candidate for the evolution of UV protection on skin. Applying this natural oil in microemulsion formulation containing particles with nanometer size can enhance its efficacy. To prepare a stable microemulsion, it is necessary to select the appropriate surfactants. In this study, first the best combination of hydrophilic surfactant of Tween 80 with various lipophilic surfactants such as Span 20, Span 80 and Span 85 at different surfactant ratios was examined. The microemulsion formulations were assessed for particle size, zeta potential, polydispersity index, refractive index, electrical conductivity, pH value and stability. Results showed that among various samples, microemulsion containing a mixture of Tween 80 and Span 80 with the surfactant ratio of 9:1 was the best sample in terms of stability over time (six months). This sample had a lower particle size of 26.09 nm with a narrow particle size distribution. For topical application, the microemulsion based hydrogel was prepared with 0.6% Carbomer 940 as a gelling agent. The pH value and viscosity of gel formulation were 6.6 and 12.90 Pa.s, respectively, which is appropriate for topical applications. A slight enhancement of particle size inside hydrogel structure was observed after six months of the gel preparation. The clinical evolutions of formulation on guinea pig's skin were included skin scaling, skin irregularity, erythema, skin hyperpigmentation, and edema. Epidermal hyperkeratosis, hyperpigmentation, exocytosis, acanthosis, chromatin discoloration in nucleus of epidermal squamous cells, perifolliculitis, dermal vascular hyperemia, edema and dermal thickness, infiltration of plasma cell lymphocytes and eosinophils into dermis were observed for histopathological investigations. Based on clinical and histopathological examinations, topical application of microemulsion-based hydrogel of sesame oil can effectively prevent skin damage induced by UV radiation and is therefore suitable for skin products.

The purpose of this study was to investigate whether the conjugation of anti-HER2-Affibody to cisplatin PEGylated liposome can efficiently enhance the therapeutic effectiveness of the targeted liposome.First, Affibody molecules were incubated with Mal-PEG2000-DSPE micelle to afford formation of a maleimide-mediated thioether coupling to the COOH-terminal cysteine of Affibody. Cisplatin-loaded liposomes composed of hydrogenated soy phosphatidylcholine/ cholesterol/mPEG2000-DSPE (56.5:38.5:5 molar ratio) (150 mM) were prepared and characterized by their physicochemical properties. Affibody-conjugated micelles were then transferred into preformed liposomes by means of post insertion. The cytotoxicity and cellular uptake of Affibody-targeted (affisome) and nontargeted liposomes were tested in HER2(+) SK-BR-3, and the in vivo therapeutic activity was evaluated in TUBO breast cancer models.Anti-HER2 affisome demonstrated a higher amount of platinum intracellularly, and affected HER2(+)-SK-BR-3 cell death was at lower concentrations compared with its liposome counterparts. Further, cisplatin-affisome showed greater therapeutic efficiency than nontargeted liposome in HER2(+)-TUBO models. Equally promising, the affisome-treated mice did extend the survival of animals by several days and even left one tumor-free survivor.Affibody-targeting endowed cisplatin liposomes with significantly enhanced, albeit modest, therapeutic activity in HER2-overexpressing tumor model; however, further values are yet to be determined to advance clinical translation of these targeted nanoparticulates.

In this investigation, Hexadecylphosphocholine (HePC, miltefosine) was being used as a new ingredient in Pegylated liposomal doxorubicin (PLD) and different aspects of this integration such as its effect on doxorubicin (Dox) release and cell uptake, cytotoxicity of liposomes, in vivo distribution and half-life clearance time of Dox as well as median survival time were illustrated. The liposomal formulations were Pegylated liposomal doxorubicin containing 0, 0.5, 1, 2 and 4% mole ratios of HePC (HePC-PLD) and their respective Dox-free liposomes (HePC-PLs). The cells used were colon carcinoma (C26), adriamycin-resistant breast cancer (MCF-7-ADR), and B16F0 melanoma cell lines, of which C26 and B16F0 cells were exploited for tumoring in BALB/c and C57Bl/6 mice, respectively. In most cases, increase in miltefosine percentage resulted in physically liposomal instability, increased Dox delivery and toxicity and reduced blood half-life of Dox. Overall, HePC 4% -PLD and PLD differed significantly in many respects and it was considered too toxic to be injected at the same dose (15mg Dox/ kg) as PLD. Although HePC 2% -PLD could extend the median survival time marginally in comparison to PLD, the concept of HePC- containing liposomes merits further investigation.

In this research, hydrogel-based colloidosome with the shell of CaCO3 microparticles was used to encapsulate caffeine as a model flavour compound. The results of the microscopic evaluation showed that the optimum parameters to fabricate this type of colloidosome were a volume fraction of water equal to 0.2 and a weight of CaCO3 microparticles to the volume of aqueous solution equal to 0.04 g/ml. In these conditions, when CaCO3 particles were dispersed in sunflower oil and then water in oil emulsion was prepared, with adding D-gluconic acid δ-lactone, water droplets containing alginate slowly gelate with the outer layer of CaCO3 particles in micrometer hydrogels without coagulation. CaCO3 microparticles act as both a cross-linker for the alginate and a stabilizer of water in oil emulsion. After leaving for 48 h, the hydrogel colloidosomes sank to the bottom of the container as a result of gravity. In the optimum state, the colloidosomes had maximum stability and uniformity. After 5 h, this colloidosome sample continued the caffeine release in water up to 55% maximally while using mouth conditions for this sample, the release of the loaded caffeine increased 33% and reached to 73%. Kinetics release of caffeine from colloidosome samples was evaluated using the spectrophotometery method and the measurement of the released caffeine concentration. The results of modelling showed that the Korsmeyer–Peppas model is the best model for describing the release behaviour in mouth conditions (R2 ≥ 0.991), whereas the Kopcha model had the maximum coefficient of determination in conditions without shear (R2 ≥ 0.968). Overall, release in all colloidosome samples was from the Fickian diffusion type. Copyright © 2015 John Wiley & Sons, Ltd.

BACKGROUND: Despite almost the three decades passed since the chemical attacks of Iraqi's army against the Iranian troops, some veterans are still suffering from long-term complications of sulfur mustard (SM) poisoning, including certain skin complaints specially dryness, burning, and pruritus. We thus aimed to evaluate the skin's water and lipid content in patients with a disability of >25% due to complications of SM poisoning and compare them with a matched control group. MATERIALS AND METHODS: Sixty-nine male participants were included in this study; 43 SM-exposed patients, and 26 normal controls from their close relatives. The water and lipid content was measured in four different locations: Extensor and flexor sides of forearms and lateral and medial sides of legs by the Corneometer CM 820/Sebumeter SM 810. Collected data was analyzed and P ≤ 0.05 was considered as statistically significant. RESULTS: The mean age of the patients and controls was 49.53 ± 11.34 (ranges: 40-71) and 29.08 ± 8.836 (ranges: 15-49 years), respectively. In the veterans group, the main cutaneous complaint was itching and skin dryness. Cherry angioma, dry skin, and pruritus were significantly more common in the SM-exposed cases than in the controls. (P = 0.01, 0.05, and 0.04, respectively). The moisture and lipid content of all areas were lower in the SM-exposed group, but it was only significant in skin sebum of lateral sides of legs (P = 0.02). CONCLUSION: Exposure to SM could decrease the function of stratum corneum and lipid production as a barrier, even after several years of its exposure. Language: en

Solid lipid nanoparticles (SLNs), as alternative colloidal carriers, have been used for the sustained release of lipophilic drugs with poor water solubility. One of the most important parameters in the characterization of SLNs is entrapment efficiency (EE). Despite the importance of this factor in estimating the drug loading capacity, EE does not always represent the exact percentage of the entrapped drug. Several variables such as the stirring speed and duration, and concentration of surfactant, emulsifier, and drug play important roles in determining the final EE. In addition, EE is mainly affected by the type and concentration of the lipid. There are two major methods for the measurement of EE are in which the encapsulated drug in SLNs is either directly measured (direct method) or the amount of unencapsulated drug in the supernatant is measured (indirect method). Accuracy of drug analysis is the main challenge for EE calculation, and is either performed in the separated aqueous medium or the particles. In this review, we aimed to introduce the available methods for EE determination in SLNs and discuss the advantages and shortcomings of each method.

This study reports on the activity of thermosensitive liposomes (TSLs) incorporating different HSPC ratios in DPPC/MSPC/PEG2000-DSPE matrix (90/10/4) plus mild hyperthermia (HT) (42 °C). TSLs were loaded with a poorly membrane permeable anticancer drug, cisplatin, through the passive equilibration method. The addition of HSPC to the corresponding DPPC lipid matrix increased the transition temperature. In vitro data demonstrated >90% cisplatin leakage from nanosized DPPC 90-lyso-TSL (LTSL) within 10 min at 42 °C, while other TSLs bearing HSPC showed greater stability. The plasma kinetics of cisplatin demonstrated higher cisplatin leakage from DPPC 90-LTSL in the first 4 h (from 17.4 to 0.4 μg/mL) compared to other formulations. Indeed, increasing HSPC fraction in liposome bilayers significantly improved drug retention in blood. Though DPPC 90-LTSL plus one-step HT was expected to provide a unique drug release, the premature drug leakage as well as the likely wash-back of a great portion of drug into the bl...

Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator which is orally used for treatment of osteoporosis and prevention of breast cancer. The drug has low aqueous solubility and bioavailability. The aim of the present study is to formulate and characterize oil-in-water microemulsion systems for oral delivery of RLX. To enhance the drug aqueous solubility, microemulsion based on sesame oil was prepared. Sesame oil and Tween 80 were selected as the drug solvent oil and surfactant, respectively. In the first and second formulations, Edible glycerin and Span 80 were applied as co-surfactant, respectively. Pseudo-ternary phase diagrams showed that the best surfactant/co-surfactant ratios in the first and second formulations were 4:1 and 9:1, respectively. The particle size of all free drug-loaded and drug loaded samples were in the range of 31.25 ± 0.3 nm and 60.9 ± 0.1 nm, respectively. Electrical conductivity coefficient and refractive index of all microemulsion samples confirmed the formation of oil-in-water type of microemulsion. In vitro drug release profile showed that after 24 hours, 46% and 63% of the drug released through the first formulation in 0.1% (w/v) Tween 80 in distilled water as a release medium and phosphate buffer solution (PBS) at pH = 5.5, respectively. These values were changed to 57% and 98% for the second formulation. Results confirmed that the proposed microemulsion system containing RLX could improve and control the drug release profile in comparison to conventional dosage form.

The aim of this study was to prepare and characterize topical methotrexate (MTX) with different percentages (0.05%, 0.1%, 0.25% and 0.5%) entrapped in deformable liposomes using phosphatidylcholine and oleic acid. The effectiveness and sub-acute toxicity of these topical formulations were investigated in imiquimod (IMQ)-induced psoriasis in a mouse model (IMQP). The particle sizes of formulations were around 100 nm with a mean zeta potential of −72.87 mV. The entrapment efficiency (EE%) of MTX in liposomal formulations were more than 85%. Franz cell permeability studies indicated that permeation of MTX through the healthy BALB/c mice skin is very low; however, in the inflammatory skin, which was induced by IMQ it was significant (50%). Liposomal MTX (LM 0.05 and 0.1%) caused significant reduction of thickness score dose-dependently in IMQP compared to the injected MTX. Moreover, investigation of the inflammatory factor and pathological examinations of skin proved the superiority of the LM treating group. Pathological examinations also showed there are no toxicity in organs of the mice that received the LM. Blood cell count test didn’t show any abnormality. MTX-entrapped deformable liposomes could be a topical option in future for the treatment of human psoriasis with a less toxicity and merit further investigations.

It has been proved that fresh frog skin is efficient in the wound healing process.The purpose of study is to introduce a formulation of frog skin powder for evaluation of wound repair where fresh frog skin is not available.Rana ridibunda (Ranidae) skins were lyophilized, and a powder was prepared. The powder (0.0005 g) was then mixed with ointment (0.0065 g) for treating each wound. Formulation was used on full-thickness wounds on mice (FO group) and compared to positive and negative controls. In order to study the wound healing process, wound contraction, inflammation, number of fibroblast cells, neovascularization and collagen density were evaluated on days 2, 4 and 6 following the injury. Moreover, CFU measurement was performed for the evaluation of wound contamination.Acceleration in wound contraction in the FO group compared to control groups was significant (p 0.001) on days 4 and 6. Results showed that FO treatment considerably decreased inflammatory cells during the study. On day 4, FO treatment was significantly effective in increasing the number of fibroblast cells and collagen density (p 0.01 and p 0.05, respectively). On day 6 the number of fibroblast cells (p 0.001), collagen density (p 0.05) and neovascularization (p 0.05), were higher in the FO group than the control groups. Results of CFU measurement demonstrated significant reduction of wound contamination in FO treated wounds on days 2 (p 0.05) and 4 (p 0.01).Our findings indicated that the pharmaceutical form of frog skin used in this study has considerable healing and antibacterial effects on wounds.