Shifting Paradigms and Arising Concerns in Severe Hemophilia A Treatment.

The management of hemophilia A has undergone a remarkable revolution, in line with technological advancement. In the recent past, the primary concern associated with Factor VIII (FVIII) concentrates was the risk of infections, which is now almost resolved by advanced blood screening and viral inactivation methods. Improving patients' compliance with prophylaxis has become a key focus, as it can lead to improved health outcomes and reduced health care costs in the long term. Recent bioengineering research is directed toward prolonging the recombinant FVIII (rFVIII) coagulant activity and synthesising higher FVIII yields. As an outcome, B-domain deleted, polyethylene glycolated, single-chain, Fc-fused rFVIII, and rFVIIIFc-von Willebrand Factor-XTEN are available for patients. Moreover, emicizumab, a bispecific antibody, is commercially available, whereas fitusiran and tissue factor pathway inhibitor are in clinical trial stages as alternative strategies for patients with inhibitors. With these advancements, noninfectious complications, such as inhibitor development, allergic reactions, and thrombosis, are emerging concerns requiring careful management. In addition, the recent approval of gene therapy is a major milestone toward a permanent cure for hemophilia A. The vast array of treatment options at our disposal today empowers patients and providers alike, to tailor therapeutic regimens to the unique needs of each individual. Despite significant progress in modern treatment options, these highly effective therapies are markedly more expensive than conventional replacement therapy, limiting their access for patients in developing countries.

Size-Controlled Preparation of Docetaxel- and Curcumin-Loaded Nanoemulsions for Potential Pulmonary Delivery.

Lung cancer is one of the deadliest pulmonary diseases in the world. Although docetaxel (DTX) has exhibited superior efficacy in lung cancer treatment, it has demonstrated numerous adverse effects and poor bioavailability. The natural product extract, curcumin (CCM), has reportedly reduced toxicity and synergistically improved DTX bioavailability. Nonetheless, the hydrophobic nature of DTX and CCM limits their clinical use. Nanoemulsion pulmonary delivery of DTX and CCM has demonstrated potential as a drug carrier to alleviate these drawbacks. The controlled preparation of inhalable DTX- and CCM-loaded nanoemulsions within the 100 to 200 nm range was explored in this study. A response surface methodology (RSM) based on a central composite design (CCD) was utilized to fabricate the desired size of the nanoemulsion under optimized conditions. Different process parameters were employed to control the size of the nanoemulsions procured through a high-energy emulsification technique. The size of the resultant nanoemulsions decreased with increasing energy input. The actual response according to the targeted sizes for DTX- and CCM-loaded nanoemulsion models exhibited excellent agreement with the predicted value at below 5% residual standard error under optimized conditions. The nanoemulsion of 100 nm particle size demonstrated better membrane permeability than their larger counterparts. Moreover, the formulations documented favorable physicochemical and aerodynamic pulmonary delivery properties and reduced toxicity in human lung fibroblast (MRC-5) cells. Hence, this tunable size of nanoemulsions could be a suitable alternative drug delivery for pulmonary diseases with increased local lung concentration.

Correction: Lipid-based nanoparticles for psoriasis treatment: a review on conventional treatments, recent works, and future prospects.

[This corrects the article DOI: 10.1039/D1RA06087B.].

A Review on the Delivery of Plant-Based Antidiabetic Agents Using Nanocarriers: Current Status and Their Role in Combatting Hyperglycaemia.

Diabetes mellitus is a prevalent metabolic syndrome that is associated with high blood glucose levels. The number of diabetic patients is increasing every year and the total number of cases is expected to reach more than 600 million worldwide by 2045. Modern antidiabetic drugs alleviate hyperglycaemia and complications that are caused by high blood glucose levels. However, due to the side effects of these drugs, plant extracts and bioactive compounds with antidiabetic properties have been gaining attention as alternative treatments for diabetes. Natural products are biocompatible, cheaper and expected to cause fewer side effects than the current antidiabetic drugs. In this review, various nanocarrier systems are discussed, such as liposomes, niosomes, polymeric nanoparticles, nanoemulsions, solid lipid nanoparticles and metallic nanoparticles. These systems have been applied to overcome the limitations of the current drugs and simultaneously improve the efficacy of plant-based antidiabetic drugs. The main challenges in the formulation of plant-based nanocarriers are the loading capacity of the plant extracts and the stability of the carriers. A brief review of lipid nanocarriers and the amphipathic properties of phospholipids and liposomes that encapsulate hydrophilic, hydrophobic and amphiphilic drugs is also described. A special emphasis is placed on metallic nanoparticles, with their advantages and associated complications being reported to highlight their effectiveness for treating hyperglycaemia. The present review could be an interesting paper for researchers who are working in the field of using plant extract-loaded nanoparticles as antidiabetic therapies.

Investigation and Optimization of Hydrogel Microneedles for Transdermal Delivery of Caffeine.

Caffeine is therapeutically effective for treating apnea, cellulite formation, and pain management. It also exhibits neuroprotective and antioxidant activities in different models of Parkinson's disease and Alzheimer's disease. However, caffeine administration in a minimally invasive and sustainable manner through the transdermal route is challenging owing to its hydrophilic nature. Therefore, this study demonstrated a transdermal delivery approach for caffeine by utilizing hydrogel microneedle (MN) as a permeation enhancer. The influence of formulation parameters such as molecular weight (MW) of PMVE/MA (polymethyl vinyl ether/maleic anhydride) copolymer and sodium bicarbonate (NaHCO3) concentration on the swelling kinetics and mechanical integrity of the hydrogel MNs was investigated. In addition, the effect of different MN application methods and needle densities of hydrogel MN on the skin insertion efficiency and penetration depth was also evaluated. The swelling degree at equilibrium percentage (% Seq) recorded for hydrogels fabricated with Gantrez S-97 (MW = 1,500,000 Da) was significantly higher than formulation with Gantrez AN-139 (MW = 1,080,000 Da). Increasing the concentration of NaHCO3 also significantly increased the % Seq. Moreover, a 100% penetration was recorded for both the applicator and combination of applicator and thumb pressure compared with only 11% for thumb pressure alone. The average diameter of micropores created by the applicator method was 62.94 µm, which was significantly lower than the combination of both applicator and thumb pressure MN application (100.53 µm). Based on histological imaging, the penetration depth of hydrogel MN increased as the MN density per array decreased. The hydrogel MN with the optimized formulation and skin insertion parameters was tested for caffeine delivery in an in vitro Franz diffusion cell setup. Approximately 2.9 mg of caffeine was delivered within 24 h, and the drug release profile was best fitted to the Korsmeyer-Peppas model, displaying Super Case II kinetics. In conclusion, a combination of thumb and impact application methods and reduced needle density improved the skin penetration efficiency of hydrogel MNs. The results also show that hydrogel MNs fabricated from 3% w/w NaHCO3 and high MW of copolymer exhibit optimum physical and swelling properties for enhanced transdermal delivery.

Nanoemulsions: A Review on the Conceptualization of Treatment for Psoriasis Using a 'Green' Surfactant with Low-Energy Emulsification Method.

Psoriasis is a skin disease that is not lethal and does not spread through bodily contact. However, this seemingly harmless condition can lead to a loss of confidence and social stigmatization due to a persons' flawed appearance. The conventional methods of psoriasis treatment include taking in systemic drugs to inhibit immunoresponses within the body or applying topical drugs onto the surface of the skin to inhibit cell proliferation. Topical methods are favored as they pose lesser side effects compared to the systemic methods. However, the side effects from systemic drugs and low bioavailability of topical drugs are the limitations to the treatment. The use of nanotechnology in this field has enhanced drug loading capacity and reduced dosage size. In this review, biosurfactants were introduced as a 'greener' alternative to their synthetic counterparts. Glycolipid biosurfactants are specifically suited for anti-psoriatic application due to their characteristic skin-enhancing qualities. The selection of a suitable oil phase can also contribute to the anti-psoriatic effect as some oils have skin-healing properties. The review covers the pathogenic pathway of psoriasis, conventional treatments, and prospective ingredients to be used as components in the nanoemulsion formulation. Furthermore, an insight into the state-of-the-art methods used in formulating nanoemulsions and their progression to low-energy methods are also elaborated in detail.

Aerosolized Niosome Formulation Containing Gemcitabine and Cisplatin for Lung Cancer Treatment: Optimization, Characterization and In Vitro Evaluation.

Gemcitabine (Gem) and cisplatin (Cis) are currently being used for lung cancer treatment, but they are highly toxic in high dosages. This research aimed to develop a niosome formulation containing a low-dosage Gem and Cis (NGC), as an alternative formulation for lung cancer treatment. NGC was prepared using a very simple heating method and was further optimized by D-optimal mixture design. The optimum NGC formulation with particle size, polydispersity index (PDI), and zeta potential of 166.45 nm, 0.16, and -15.28 mV, respectively, was obtained and remained stable at 27 °C with no phase separation for up to 90 days. The aerosol output was 96.22%, which indicates its suitability as aerosolized formulation. An in vitro drug release study using the dialysis bag diffusion technique showed controlled release for both drugs up to 24 h penetration. A cytotoxicity study against normal lung (MRC5) and lung cancer (A549) cell lines was investigated. The results showed that the optimized NGC had reduced cytotoxicity effects against both MRC5 and A549 when compared with the control (Gem + Cis alone) from very toxic (IC50 < 1.56 µg/mL) to weakly toxic (IC50 280.00 µg/mL) and moderately toxic (IC50 = 46.00 µg/mL), respectively, after 72 h of treatment. These findings revealed that the optimized NGC has excellent potential and is a promising prospect in aerosolized delivery systems to treat lung cancer that warrants further investigation.

Lipid-based nanoparticles for psoriasis treatment: a review on conventional treatments, recent works, and future prospects.

Psoriasis is a lingering inflammatory skin disease that attacks the immune system. The abnormal interactions between T cells, immune cells, and inflammatory cytokines causing the epidermal thickening. International guidelines have recommended topical treatments for mild to moderate psoriasis whilst systemic and phototherapy treatments for moderate to severe psoriasis. However, current therapeutic approaches have a wider extent to treat moderate to severe type of psoriasis especially since the emergence of diverse biologic agents. In the meantime, topical delivery of conventional treatments has prompted many unsatisfactory effects to penetrate through the skin (stratum corneum). By understanding the physiology of stratum corneum barrier functions, scientists have developed different types of lipid-based nanoparticles like solid lipid nanoparticles, nanostructured lipid carriers, nanovesicles, and nanoemulsions. These novel drug delivery systems help the poorly solubilised active pharmaceutical ingredient reaches the targeted site seamlessly because of the bioavailability feature of the nanosized molecules. Lipid-based nanoparticles for psoriasis treatments create a paradigm for topical drug delivery due to their lipids' amphiphilic feature to efficiently encapsulate both lipophilic and hydrophilic drugs. This review highlights different types of lipid-based nanoparticles and their recent works of nano formulated psoriasis treatments. The encapsulation of psoriasis drugs through lipid nanocarriers unfold numerous research opportunities in pharmaceutical applications but also draw challenges for the future development of nano drugs.

Extraction, anti-tyrosinase, and antioxidant activities of the collagen hydrolysate derived from Rhopilema hispidum.

The study was conducted to determine anti-tyrosinase and antioxidant activities of the extracted collagen hydrolysate (CH) derived from Malaysian jellyfish, Rhopilema hispidum. Collagen was extracted using 1:1 (w:v) 0.1 M NaOH solution at temperature 25 °C for 48 hr followed by treatment of 1:2 (w:v) distilled water for another 24 hr and freeze-dried. The extracted collagen was hydrolyzed using papain at optimum temperature, pH and enzyme/substrate ratio [E/S] of 60 °C, 7.0 and 1:50, respectively. CH was found to exhibit tyrosinase inhibitory activity, DPPH radical scavenging and metal ion-chelating assays up to 64, 28, and 83%, respectively, after 8 hr of hydrolysis process. The molecular weight of CH was found <10 kDa consisting of mainly Gly (19.219%), Glu (10.428%), and Arg (8.848%). The UV-visible spectrum analysis showed a major and minor peak at 218 and 276 nm, accordingly. The FTIR spectroscopy confirmed the amide groups in CH. The SEM images demonstrated spongy and porous structure of CH. In the cytotoxicity study, CH has no cytotoxicity against mouse embryonic 3T3 fibroblast cell line with IC50 value >500 µg/ml. Results revealed that the CH generated from this study has a potential to be developed as active ingredient in cosmeceutical application.

Response Factorial Design Analysis on Papain-Generated Hydrolysates from Actinopyga lecanora for Determination of Antioxidant and Antityrosinase Activities.

Actinopyga lecanora (A. lecanora) is classified among the edible species of sea cucumber, known to be rich in protein. Its hydrolysates were reported to contain relatively high antioxidant activity. Antioxidants are one of the essential properties in cosmeceutical products especially to alleviate skin aging. In the present study, pH, reaction temperature, reaction time and enzyme/substrate ratio (E/S) have been identified as the parameters in the papain enzymatic hydrolysis of A. lecanora. The degree of hydrolysis (DH) with antioxidant activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP) assays were used as the responses in the optimization. Analysis of variance (ANOVA), normal plot of residuals and 3D contour plots were evaluated to study the effects and interactions between parameters. The best conditions selected from the optimization were at pH 5.00, 70 °C of reaction temperature, 9 h of hydrolysis time and 1.00% enzyme/substrate (E/S) ratio, with the hydrolysates having 51.90% of DH, 42.70% of DPPH activity and 109.90 Fe2+µg/mL of FRAP activity. The A. lecanora hydrolysates (ALH) showed a high amount of hydrophobic amino acids (286.40 mg/g sample) that might be responsible for antioxidant and antityrosinase activities. Scanning electron microscopy (SEM) image of ALH shows smooth structures with pores. Antityrosinase activity of ALH exhibited inhibition of 31.50% for L-tyrosine substrate and 25.40% for L-DOPA substrate. This condition suggests that the optimized ALH acquired has the potential to be used as a bioactive ingredient for cosmeceutical applications.

Modeling the Effect of Composition on Formation of Aerosolized Nanoemulsion System Encapsulating Docetaxel and Curcumin Using D-Optimal Mixture Experimental Design.

The synergistic anticancer effect of docetaxel (DTX) and curcumin (CCM) has emerged as an attractive therapeutic candidate for lung cancer treatment. However, the lack of optimal bioavailability because of high toxicity, low stability, and poor solubility has limited their clinical success. Given this, an aerosolized nanoemulsion system for pulmonary delivery is recommended to mitigate these drawbacks. In this study, DTX- and CCM-loaded nanoemulsions were optimized using the D-optimal mixture experimental design (MED). The effect of nanoemulsion compositions towards two response variables, namely, particle size and aerosol size, was studied. The optimized formulations for both DTX- and CCM-loaded nanoemulsions were determined, and their physicochemical and aerodynamic properties were evaluated as well. The MED models achieved the optimum formulation for DTX- and CCM-loaded nanoemulsions containing a 6.0 wt% mixture of palm kernel oil ester (PKOE) and safflower seed oils (1:1), 2.5 wt% of lecithin, 2.0 wt% mixture of Tween 85 and Span 85 (9:1), and 2.5 wt% of glycerol in the aqueous phase. The actual values of the optimized formulations were in line with the predicted values obtained from the MED, and they exhibited desirable attributes of physicochemical and aerodynamic properties for inhalation therapy. Thus, the optimized formulations have potential use as a drug delivery system for a pulmonary application.

Optimization of Processing Parameters of Nanoemulsion Containing Aripiprazole Using Response Surface Methodology.

BACKGROUND: Aripiprazole, which is a quinolinone derivative, has been widely used to treat schizophrenia, major depressive disorder, and bipolar disorder. PURPOSE: A Central Composite Rotatable Design (CCRD) of Response Surface Methodology (RSM) was used purposely to optimize process parameters conditions for formulating nanoemulsion containing aripiprazole using high emulsification methods. METHODS: This design is used to investigate the influences of four independent variables (overhead stirring time (A), shear rate (B), shear time (C), and the cycle of high-pressure homogenizer (D)) on the response variable namely, a droplet size (Y) of nanoemulsion containing aripiprazole. RESULTS: The optimum conditions suggested by the predicted model were: 120 min of overhead stirring time, 15 min of high shear homogenizer time, 4400 rpm of high shear homogenizer rate and 11 cycles of high-pressure homogenizer, giving a desirable droplet size of nanoemulsion containing aripiprazole of 64.52 nm for experimental value and 62.59 nm for predicted value. The analysis of variance (ANOVA) showed the quadratic polynomial fitted the experimental values with F-value (9.53), a low p-value (0.0003) and a non-significant lack of-fit. It proved that the models were adequate to predict the relevance response. The optimized formulation with a viscosity value of 3.72 mPa.s and pH value of 7.4 showed good osmolality value (297 mOsm/kg) and remained stable for three months in three different temperatures (4°C, 25°C, and 45°C). CONCLUSION: This proven that response surface methodology is an efficient tool to produce desirable droplet size of nanoemulsion containing aripiprazole for parenteral delivery application.

In vitro kinetic release study, antimicrobial activity and in vivo toxicity profile of a kojic acid ester-based nanoemulsion for topical application.

Nanoemulsions have emerged as novel vehicles for drug delivery that allow sustained or controlled release for topical application. In this study, kojic acid ester-based nanoemulsion (KAE-NA) was analyzed for in vitro permeation evaluation, kinetic release study, in vitro antimicrobial activity and in vivo toxicity profile on embryonic zebrafish (Danio rerio). Based on KAE-NA in vitro permeation evaluation, the percentage of permeation was significantly improved from 4.94% at 1 h to 59.64% at 8 h of application. The permeation rate of KAE-NA at 8 h was 4659.50 µg cm-2 h-1 (initial concentration, C 0 = 2000 µg mL-1) with a permeability coefficient (K p) value of 0.48 cm h-1. The kinetic release analysis showed the Korsmeyer-Peppas model was the best fitted kinetic model with high linearity [R 2 = 0.9964]. Antimicrobial activity of KAE-NA was studied against the skin pathogen bacteria Staphylococcus aureus ATCC 43300. The results indicated that the inhibition zone size of the KAE-NA (8.00 ± 0.0 mm) was slightly bigger than that of its active ingredient, kojic acid ester (6.5 ± 0.0 mm). The toxicity profile of KAE-NA on embryonic zebrafish revealed less toxicity with LC50 (50% lethal concentration) more than 500 µg mL-1. The survival rate of the embryonic zebrafish was more than 80% when treated at doses ranging from 7.81-250 µg mL-1 and showed normal development throughout the experiment without any observed deformation. Hence, KAE-NA proved to be less toxic on the embryonic zebrafish.

Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells.

BACKGROUND: Gemcitabine (GEM) is a chemotherapeutic agent, which is known to battle cancer but challenging due to its hydrophilic nature. Nanoemulsion is water-in-oil (W/O) nanoemulsion shows potential as a carrier system in delivering gemcitabine to the cancer cell. METHODS: The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response. RESULTS: The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and -37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).

Optimization and Characterization of Palm Oil-based Nanoemulsion Loaded with Parthenium hysterophorus Crude Extract for Natural Herbicide Formulation.

The present study revealed the optimization of nanoemulsion containing palm oil derivatives and Parthenium hysterophorus L. crude extract (PHCE) as pre-emergence herbicide formulation against Diodia ocimifolia. The nanoemulsion formulation was prepared by high energy emulsification method, and it was optimized by mixture experimental design (MED). From the optimization process, analysis of variance (ANOVA) showed a fit quadratic polynomial model with an optimal formulation composition containing 30.91% of palm kernel oil ester (PKOE), 28.48% of mixed surfactants (Tensiofix and Tween 80, 8:2), 28.32% of water and 12.29% of PHCE. The reading of both experimental and predicted particle size in the verification experiment were acceptable with a residual standard error (RSE) was less than 2%. Under the optimal condition, the smallest particle size obtained was 140.10 nm, and the particle was shown by morphology analysis to be spherical and demonstrated good stability (no phase separation) under centrifugation and different storage conditions (25 ± 5°C and 45°C). Nanoemulsion stored for 60 days exhibits monodisperse emulsion with a slight increase of particle size. The increase in particle size over time might have contributed by Ostwald ripening phenomenon which is shown by a linear graph from Ostwald ripening rate analysis. In the in vitro germination test, P. hysterophorus nanoemulsion (PHNE) was shown to cause total inhibition of D. ocimifolia seed at lower concentration (5 g L-1) as compared to PHCE (10 g L-1). The finding of the research could potentially serve as a platform for the development of palm oil based formulation containing plant crude extract for green weed management.

Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment.

Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and ζ-potential in the range of 90 to 110 nm and - 30 to - 40 mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 ± 1 °C for 3 months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery.

In vitro evaluation of the inhalable quercetin loaded nanoemulsion for pulmonary delivery.

Bioavailability of quercetin, a flavonoid potentially known to combat cancer, is challenging due to hydrophobic nature. Oil-in-water (O/W) nanoemulsion system could be used as nanocarrier for quercertin to be delivered to lung via pulmonary delivery. The novelty of this nanoformulation was introduced by using palm oil ester/ricinoleic acid as oil phase which formed spherical shape nanoemulsion as measured by transmission electron microscopy and Zetasizer analyses. High energy emulsification method and D-optimal mixture design were used to optimize the composition towards the volume median diameter. The droplet size, polydispersity index, and zeta potential of the optimized formulation were 131.4 nm, 0.257, and 51.1 mV, respectively. The formulation exhibited high drug entrapment efficiency and good stability against phase separation and storage at temperature 4 °C for 3 months. It was discovered that the system had an acceptable median mass aerodynamic diameter (3.09 ± 0.05 µm) and geometric standard deviation (1.77 ± 0.03) with high fine particle fraction (90.52 ± 0.10%), percent dispersed (83.12 ± 1.29%), and percent inhaled (81.26 ± 1.28%) for deposition in deep lung. The in vitro release study demonstrated that the sustained release pattern of quercetin from naneomulsion formulation up to 48 h of about 26.75% release and it was in adherence to Korsmeyer's Peppas mechanism. The cytotoxicity study demonstrated that the optimized nanoemulsion can potentially induce cyctotoxicity towards A549 lung cancer cells without affecting the normal cells. These results of the study suggest that nanoemulsion is a potential carrier system for pulmonary delivery of molecules with low water solubility like quercetin.

Improvement of physicochemical properties of nanocolloidal carrier loaded with low water solubility drug for parenteral cancer treatment by Response Surface Methodology.

Nanoemulsions have been used as a drug carrier system, particularly for poorly water-soluble drugs. Sorafenib is a poorly soluble drug and also there is no parenteral treatment. The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib. The formulations were prepared by high energy emulsification method and optimized by using Response Surface Methodology (RSM). Here, the effect of independent composition variables of lecithin (1.16-2.84%, w/w), Medium-Chain Triglycerides (2.32-5.68%, w/w) and polysorbate 80 (0.58-1.42%, w/w) amounts on the properties of Sorafenib-loaded nanoemulsion was investigated. The three responses variables were particle size, zeta potential, and polydispersity index. Optimization of the conditions according to the three dependent variables was performed for the preparation of the Sorafenib-loaded nanoemulsions with the minimum value of particle size, suitable rage of zeta potential, and polydispersity index. A formulation containing 0.05% of Sorafenib kept its properties in a satisfactory range over the evaluated period. The composition with 3% Medium-Chain Triglycerides, 2.5% lecithin and 1.22% polysorbate 80 exhibited the smallest particle size and polydispersity index (43.17 nm and 0.22, respectively) with the zeta potential of -38.8 mV was the optimized composition. The fabricated nanoemulsion was characterized by the transmission electron microscope (TEM), viscosity, and stability assessment study. Also, the cytotoxicity result showed that the optimum formulations had no significant effect on a normal cell in a low concentration of the drug but could eliminate the cancer cells. The dose-dependent toxicity made it a suitable candidate for parenteral applications in the treatment of breast cancer. Furthermore, the optimized formulation indicated good storage stability for 3 months at different temperatures (4 ±â€¯2 °C, 25 ±â€¯2 °C and 45 ±â€¯2 °C).

Development of a kojic monooleate-enriched oil-in-water nanoemulsion as a potential carrier for hyperpigmentation treatment.

INTRODUCTION: Kojic monooleate (KMO) is an ester derived from a fungal metabolite of kojic acid with monounsaturated fatty acid, oleic acid, which contains tyrosinase inhibitor to treat skin disorders such as hyperpigmentation. In this study, KMO was formulated in an oil-in-water nanoemulsion as a carrier for better penetration into the skin. METHODS: The nanoemulsion was prepared by using high and low energy emulsification technique. D-optimal mixture experimental design was generated as a tool for optimizing the composition of nanoemulsions suitable for topical delivery systems. Effects of formulation variables including KMO (2.0%-10.0% w/w), mixture of castor oil (CO):lemon essential oil (LO; 9:1) (1.0%-5.0% w/w), Tween 80 (1.0%-4.0% w/w), xanthan gum (0.5%-1.5% w/w), and deionized water (78.8%-94.8% w/w), on droplet size as a response were determined. RESULTS: Analysis of variance showed that the fitness of the quadratic polynomial fits the experimental data with F-value (2,479.87), a low P-value (P<0.0001), and a nonsignificant lack of fit. The optimized formulation of KMO-enriched nanoemulsion with desirable criteria was KMO (10.0% w/w), Tween 80 (3.19% w/w), CO:LO (3.74% w/w), xanthan gum (0.70% w/w), and deionized water (81.68% w/w). This optimum formulation showed good agreement between the actual droplet size (110.01 nm) and the predicted droplet size (111.73 nm) with a residual standard error <2.0%. The optimized formulation with pH values (6.28) showed high conductivity (1,492.00 µScm-1) and remained stable under accelerated stability study during storage at 4°C, 25°C, and 45°C for 90 days, centrifugal force as well as freeze-thaw cycles. Rheology measurement justified that the optimized formulation was more elastic (shear thinning and pseudo-plastic properties) rather than demonstrating viscous characteristics. In vitro cytotoxicity of the optimized KMO formulation and KMO oil showed that IC50 (50% inhibition of cell viability) value was >100 µg/mL. CONCLUSION: The survival rate of 3T3 cell on KMO formulation (54.76%) was found to be higher compared to KMO oil (53.37%) without any toxicity sign. This proved that the KMO formulation was less toxic and can be applied for cosmeceutical applications.

Optimization of Quercetin loaded Palm Oil Ester Based Nanoemulsion Formulation for Pulmonary Delivery.

In this research, the palm oil ester (POE)- based nanoemulsion formulation containing quercetin for pulmonary delivery was developed. The nanoemulsion formulation was prepared by high energy emulsification method and then further optimized using D-optimal mixture design. The concentration effects of the mixture of POE:ricinoleic acid (RC), ratio 1:1 (1.50-4.50 wt.%), lecithin (1.50-2.50 wt.%), Tween 80 (0.50-1.00 wt.%), glycerol (1.50-3.00 wt.%), and water (88.0-94.9 wt.%) towards the droplet size were investigated. The results showed that the optimum formulation with 1.50 wt.% POE:RC, 1.50 wt.% lecithin, 1.50 wt.% Tween 80, 1.50 wt.% glycerol and 93.90 % water was obtained. The droplet size, polydispersity index (PDI) and zeta potential of the optimized formulation were 110.3 nm, 0.290 and －37.7 mV, respectively. The formulation also exhibited good stability against storage at 4℃ for 90 days. In vitro aerosols delivery evaluation showed that the aerosols output, aerosols rate and median mass aerodynamic diameter of the optimized nanoemulsion were 99.31%, 0.19 g/min and 4.25 µm, respectively. The characterization of physical properties and efficiency for aerosols delivery results suggest that POE- based nanoemulsion containing quercetin has the potential to be used for pulmonary delivery specifically for lung cancer treatment.