Green Formulation of Spironolactone Loaded Chitosan-Coated Nano Lipid Carrier for Treatment of Acne Vulgaris: A Randomized Double-Blind Clinical Trial.

Purpose: Spironolactone (SPN), which is classified as an anti-androgen, has demonstrated efficacy in treating acne. This study aimed to utilize ultrasonication to create a chitosan-coated nano lipid carrier (NLC) for enhancing the delivery of SPN to the skin and treating acne. Methods: Various hydrophilic-lipophilic balance (HLB) values were investigated to optimize the SPN-NLCs. Photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were employed to characterize the solid state of SPN in nanoparticle form. Additionally, the optimized formulation was used in a double-blind, randomized clinical trial. Results: Reducing the HLB of the surfactant mixtures resulted in a reduction in the size of SPNNLCs. The formula with the smallest particle diameter (238.4±0.74 nm) and the lowest HLB value (9.65) exhibited the highest encapsulation efficiency (EE) of 79.88±1.807%. Coating the optimized SPN-NLC with chitosan increased the diameter, polydispersity index (PDI), zeta potential (ZP), and EE. In vitro skin absorption studies demonstrated sustained release profiles for chitosan-coated SPN-NLC. In the double-blind trial, a gel containing chitosan-coated SPN-NLC effectively treated mild to moderate acne vulgaris, leading to improved healing and reduced lesion count after 8 weeks of therapy compared to the placebo. It successfully addressed both non-inflammatory and inflammatory lesions without adverse effects on the skin. Conclusion: The findings indicate that chitosan-coated SPN-NLCs have the potential as nanoparticles for targeted SPN delivery to the skin, offering novel options for the treatment of acne vulgaris.

Vitamin K (Menadione)-incorporated chitosan/alginate hydrogel as a novel product for periorbital hyperpigmentation.

The possibility of controlling periorbital hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. In the current investigation, 1% vitamin K (Vit K) was incorporated into a Chitosan/alginate hydrogel which aimed to increase the dermal delivery and anti-pigmentation effect. The Vit K-hydrogel was evaluated using several different tests, including volume expansion/contraction analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), ultraviolet (UV) absorbance spectroscopy, and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Vit K hydrogel's drug release profile showed a steady increase over time. Furthermore, the modified Vit K hydrogel formulations showed no harmful effects in an in vitro cytotoxicity study. The Vit K hydrogel was tested for dermal irritation on Wistar rats, and the hydrogel was found to be non-irritating. Furthermore, Vit K-hydrogel inhibited melanin formation (31.76 ± 1.14%) and was remarkably higher than free Vit K. In addition, Vit K-hydrogel inhibited L-dopa auto-oxidation to a greater extent (94.80 ± 2.41%) in comparison with Vit K solution (73.95 ± 1.62%). Vit K-hydrogel enhanced percutaneous transport of Vit K, according to in vitro percutaneous absorption findings, suggesting that this innovative formulation may provide new therapeutic options for periorbital hyperpigmentation.

Development of kojic acid loaded collagen-chitosan nanoparticle as skin lightener product: in vitro and in vivo assessment.

In the present study, an ionic gelation and ultrasonic approach was performed to produce kojic acid (KA) loaded chitosan(CS)/collagen(CN) nanoparticle(NP) (CSCN-NP) which aimed to increase the dermal delivery and anti-pigmentation effect. To optimize the CSCN-NP the effect of the amount of CN was investigated. The results showed that increasing CN from 0 to 500 mg increased the mean particle size and entrapment efficiency of KA-CSCN-NP from 266.07 ± 9.30 nm to 404.23 ± 9.44 nm and 17.37 ± 2.06% to 82.34 ± 2.16%, respectively. Differential scanning calorimetry confirmed the amorphous form of KA in CSCN-NP, while scanning electron microscopy revealed that the nanoparticles were spherical. There was no chemical interaction between KA and the other components base on attenuated total reflectance-Fourier transform infrared spectroscopy. The skin permeability test showed that KA-CSCN-NP gel delivered more KA to the dermal layers (29.16 ± 1.67% or 537.26 ± 537.26 µg/cm2) and receiver compartment (15.04 ± 1.47% or 277.15 ± 27.22 µg/cm2) compared to KA plain gel. In vitro cytotoxicity assay demonstrated that the improved KA-CSCN-NP was non-toxic. Dermal irritating test on Wistar rats showed that the KA gel was non-irritating. Furthermore, KA-CSCN-NP was found to inhibit melanin formation to a greater extent than free KA and significantly inhibited L-dopa auto-oxidation (94.80 ± 2.41%) compared to pure kojic acid solution (75.28 ± 3.22%). The observations of this study revealed that the produced KA-CSCN-NP might be used as a potential nano-vehicle for KA dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems.

Nanohybrid Based on (Mn, Zn) Ferrite Nanoparticles Functionalized With Chitosan and Sodium Alginate for Loading of Curcumin Against Human Breast Cancer Cells.

This study reports on the synthesis of Mn1 - xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn0.8Zn0.2Fe2O4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.

Eco-friendly preparation, characterization, evaluation of anti-melanogenesis/antioxidant effect and in vitro/in vivo safety profile of kojic acid loaded niosome as skin lightener preparation.

In the current study, an ultrasonic approach (as green method) was utilized to prepared kojic acid niosome (kojisome) which aimed to increase the dermal delivery and improving anti-melanogenesis properties. The study's findings demonstrated that increasing cholesterol enhanced the mean particle size from 68.333 ± 5.686 nm to 325.000 ± 15.099 nm and entrapment efficiency 0% to 39.341 ± 4.126% of the kojisome. Cholesterol may enhance the number and rigidity of bilayers that induced a size enhancement and entrapment efficiency. The skin permeability test revealed that kojisome gel had more kojic acid in dermal layers (437.563 ± 29.857 µg/cm2 or 16.624 ± 1.379%) than kojic acid plain gel (161.290 ± 14.812 µg/cm2 or 6.128 ± 0.672%). The niosome's lipophilicity allowed for gradual penetration, possibly due to better contact with the skin layers. Also, the extended-release behavior of improved kojisome exhibited high safety profile and low side effect in In vitro cytotoxicity assay, dermal irritation test, and Histo-pathological evaluation. Furthermore, optimum kojisome inhibited melanin formation (53.093 ± 2.985% at 1000 µM) higher than free kojic acid (62.383 ± 1.958%) significantly (p < 0.05). In addition, Kojisome 6 inhibited L-dopa auto-oxidation greater extent (94.806 ± 2.411%) than pure kojic acid solution (72.953 ± 2.728%). Kojisome by delivering and targeting large amount of kojic acid on specific site causes high efficacy in inhibition of melanin synthesis. The observations of this study revealed that the produced kojisome might be used as a potential nano-vehicle for kojic acid dermal administration, thereby opening up innovative options for the treatment of hyperpigmentation problems.

Green formulation, characterization, antifungal and biological safety evaluation of terbinafine HCl niosomes and niosomal gels manufactured by eco-friendly green method.

Terbinafine (TER) is a promising candidate medication for the topical treatment of fungal infections. However, its solubility in water and skin permeability are limited. To overcome these limitations, a Terbinafine niosome and niosomal gel was developed. The impact of cholesterol:surfactants on terbinafine incorporated niosome (terbinasome) preparations was examined. Differential scanning calorimetry (DSC), photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to assess the morphological features of terbinasome and the physicochemical characteristics of TER in terbinasome. The obtained results has shown that Chol enhanced the diameter of the terbinasome from 123.20 ± 2.86 to 701.93 ± 17.72 nm. The highest encapsulation of terbinafine was estimated to be around 66% due to the cholesterol:surfactants ratio in the terbinasome was 1:3 and 1:6. Additional examination has revealed that changes in the cholesterol:surfactants ratio can result in a change in the PDI value of between 0.421 ± 0.004 and 0.712 ± 0.011. The terbinasome gel was prepared and tested for pharmaceutical testing, including pH, viscosity, spreadability, and stability. The percentage of TER dissolution from terbinasome were determined more than 80% and showed quickest drug release. In a cutaneous permeability examination, the quantity of TER in the cutaneous layers and the receiver compartment were higher for the terbinasome gel than for the TER simple gel. The terbinasome's cell viability was around 90% (HFF cell line) and MTT experiment demonstrated that the terbinasome was not cytotoxic. The MIC of the terbinasome was lower than pure drug against Aspergillus, Fusarium, and Trichophyton. The terbinasomal gels were non-irritant (score < 2) in the cutaneous irritation examination performed on Wistar rats. The research suggests that the optimized terbinasome may be used as a nano-vesicle for TER drug administration, hence opening up new possibilities for the treatment of cutaneous infections.

Green preparation, characterization, evaluation of anti-melanogenesis effect and in vitro/in vivo safety profile of kojic acid hydrogel as skin lightener formulation.

The local treatment of kojic acid (KA) as a tyrosinase inhibitor results in inadequate skin absorption and a number of side effects. The current study aims to maximize KA skin delivery. To produce KA-hydrogel, 1% KA was injected into a Chitosan/alginate hydrogel. The impacts of biopolymer proportion on the KA-hydrogel preparations were investigated. Swelling analysis, weight loss analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), UV absorption spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to evaluate the KA-hydrogel. The swelling percentages of KA-hydrogel increased significantly after 4 h. After two weeks, up to 60% of the primary mass of the KA- hydrogel has been removed. By alternation in biopolymer proportion, the drug release profile of KA-hydrogel demonstrated a sustained pattern. According to the skin absorption experiment, KA-hydrogel had higher skin deposition (25.630 ± 3.350%) than KA-plain gel (5.170 ± 0.340%). Moreover, an in vitro cytotoxicity analysis for the modified KA-hydrogel preparations revealed no cytotoxic effects on HFF cell line (90%). Moreover, KA hydrogel had inhibitory effect on melanin synthesis and are comparable with KA. Furthermore, KA-hydrogel had higher inhibitory effect on L-dopa auto oxidation (94.84 ± 2.41%) in comparison KA solution (73.95 ± 3.28%). Also, the dermal irritation study on Wistar rat revealed that the hydrogel constituent used did not irritate the skin. These results revealed that the KA-hydrogel might be employed as KA local administration, thus opening up new prospects for the therapies of hyperpigmentation problems.

Solid lipid nanoparticles and nanostructured lipid carriers: a review of the methods of manufacture and routes of administration.

The bioavailability of drugs is dependent on several factors such as solubility and the administration route. A drug with poor aqueous solubility, therefore, poses challenges with regards to its pharmaceutical advance and ultimately its biological usage. Lipid nanoparticles have been used in pharmaceutical science due to their importance in green chemistry. Their biochemical properties as 'green' materials and biochemical processes as 'green' processes mean they can be environmentally sustainable. Generally, lipid nanoparticles can be employed as carriers for both lipophilic and hydrophilic drugs. The proposed administration route for nanoparticles can present advantages and disadvantages which should be considered by a formulator. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are attractive delivery systems because of their ease of manufacture, biocompatibility, biodegradability, and scale-up capacity of formulation constituents. The easy and simple scalability of novel SLNs and nano lipid carriers, along with their various processing procedures, recent developments, limitation and toxicity, formulation optimization and approaches for the manufacture of lipid nanoparticles, lyophilization and drug release are comprehensively discussed in this review. This review also summarizes the research data related to the various preparation methods and excipients used for SLNs and NLCs in recent years.

Venlafaxine HCl Encapsulated in Niosome: Green and Eco-friendly Formulation for the Management of Pain.

The goal of this experimentation was to increase the cutaneous absorption of venlafaxine HCl (VFX) encapsulated in a niosome (venlasosme) produced by an ultrasonic approach. The impact of the cholesterol:surfactant (Chol:Surf) proportion was examined to modify the venlasosme properties. Photon correlation spectroscopy, powder X-ray diffraction (PXRD), SEM, DSC, and ATR-FTIR spectroscopy were utilized to investigate the solid-state and morphology of VFX in the venlasosme. The studies revealed that increasing the level of Chol in the venlasosme increased the size of the particles. Alterations in the Chol to surfactant ratios (when Chol decreased from 2.5 to 0%) caused the zeta potential enhancement from 7.37 ± 0.67 to 15.53 ± 1.47 mV. The venlasosme with the highest cholesterol concentration (2.5%) had the highest encapsulation efficiency (approximately 63%). PXRD results revealed that VFX in venlasosme was in the amorphous form. The levels of VFX in the cutaneous layers and the receiver compartment were higher for the venlasosme gel than for VFX simple gel in the cutaneous permeability study and showed no cutaneous irritancy in rats. Furthermore, the venlasosme gel demonstrated significant antinociceptive and anti-inflammatory responses when compared to the control groups (VFX simple gel and diclofenac gel). The topical administration of the venlasosme gel also considerably increased the tail-flick and hot-plate response time when compared to the VFX simple gel, control groups, and diclofenac gel (p < 0.05). These findings suggest that niosomes can improve VFX efficacy as an antinociceptive and anti-inflammatory substance by improving the medicaments delivery to the specified site.

Innovative topical niosomal gel formulation containing diclofenac sodium (niofenac).

The purpose of this research was to enhance the transdermal delivery of diclofenac sodium niosomal formulations. To characterise the obtained niosomes, SEM, XRPD, DSC and ATR-FTIR were employed. The size of the niosomes increased from 158.00 ± 6.17 to 400.87 ± 4.99 nm when cholesterol was incorporated into the formulations. It was observed that the zeta potential of niofenac varies from -25.40 ± 1.352 to -43.13 ± 1.171 mV when the cholesterol percentage decreased from 2% to 0.2%. The higher entrapment efficiency percentage (63.70 ± 0.18%) was obtained for the formulations with larger particle sizes and higher cholesterol content. The optimised niofenac formulation showed a controlled release fashion where 61.71 ± 0.59% of the drug released within 24 h. The results showed that the value of permeated diclofenac sodium through the skin layers was higher for the niofenac gel formulation (242.3 ± 31.11 µg/cm2) compared to simple gel formulation (127.40 ± 27.80 µg/cm2). Besides, niofenac formulation outperformed the anti-inflammatory activities in the formalin test compared to the control and diclofenac simple gel group. The licking time was significantly lower in both early (40.2 ± 7.3 s) and late stages (432.4 ± 31.7 s) for niofenac compared to conventional formulation (early stage 130.4 ± 8.73 s and late stage 660.6 ± 123.73 s). This study indicates that niosomal formulations can improve drug therapeutic effects by increasing drug delivery to specific sites.

Development of a novel nanoemulgel formulation containing cumin essential oil as skin permeation enhancer.

Essential oils have been proposed as promising non-toxic transdermal permeation enhancers. Their use is limited because of their low water solubility. The use of nanotechnology-based strategies is one of the ways to overcome this limitation. This study aimed to explore the transdermal permeation enhancing capability of cumin essential oil in nanoemulgel systems containing diclofenac sodium. Cumin essential oil nanoemulsion was produced by high-pressure homogenization technique. The formulation was optimized by changing HLB values in a range of 9.65-16.7 using different surfactant mixtures, namely, Tween 20, Tween 80, and Span 80. Preparations were characterized by polydispersity index, droplet size, and zeta potential. Nanoemulsion with concentrations of 2 and 4% essential oil was incorporated into 0.75% Carbopol gel matrix to make nanoemulgel formulation, and its permeation enhancing effect was performed through Franz diffusion cells. Antinociceptive activities of the formulations were measured in thermal (tail-flick) and chemical (formalin) models of nociception in mice. Characterization exhibited that at HLB value of 9.65, the smallest particle size (82.20 ± 5.82 nm) was formed. By increasing the essential oil percentage in the nanoemulgel from 1 to 2%, the permeation of diclofenac increased from 28.39 ± 1.23 to 34.75 ± 1.07 µg/cm2 at 24 h. The value of permeation from the simple gel (21.18 ± 2.51 µg/cm2) and the marketed product (22.97 ± 1.92 µg/cm2) was lower than the formulations containing essential oil. Nanoemulgel of diclofenac containing essential oil showed stronger antinociceptive effects in formalin and tail-flick tests than simple diclofenac gel and marketed formulation. In conclusion, the study proved that nanoemulgel formulation containing cumin essential oil could be considered as a promising skin enhancer to enhance the therapeutic effect of drugs.

Topical Gel of Vitamin A Solid Lipid Nanoparticles: A Hopeful Promise as a Dermal Delivery System.

Purpose: The Objective of the present investigation was to enhance the skin delivery of vitamin A (Vit A) via producing solid lipid nanoparticles (SLNs) through ultrasonication technique. Methods: For achieving optimal skin delivery, impacts of two surfactants ratio of Tween80:Span80 on nanoparticles (NPs) features and the respective functions were examined. Powder X-ray diffractometer (PXRD), photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were applied for characterizing the solid state of Vit A in the SLN. Results: Results showed that size of the NPs is usually enhanced by adding co-emulsifier (Span80). Notably, minimum NPs size (64.85±4.259 nm) was achieved while the hydrophilic-lipophilic balance (HLB) of the binary surfactants was 12.08, close to HLB of beeswax (HLB=12) as lipid matrix. Also, maximum entrapment efficiency (66.01±8.670%) was observed in the formulation. DSC thermogram indicated an amorphous form of Vit A in SLN. ATR-FTIR spectra of Vit A-SLN illustrated that prominent functional groups are found in the formulations that might be a sign of acceptable entrapment of Vit A in a lipid matrix. Moreover, ATR-FTIR studies showed no chemical interactions between Vit A and excipients. Skin irritation test proved the non-irritancy of Vit A-SLN2, when applied to the dorsal region of Wistar rats. Finally, any cellular toxicity was not seen for NPs. Conclusion: It was found that the procured Vit A-SLNs could be utilized as potent carriers for the dermal delivery of Vit A.

Encapsulation of bacteriophage cocktail into chitosan for the treatment of bacterial diarrhea.

The therapeutic effectiveness of a chitosan encapsulated bacteriophage cocktail as a smart biocontrol agent was evaluated in this study to be used as a preventative and treatment option for gastrointestinal infections. To evaluate the effect of the bacteriophage formulation on the treatment of gastrointestinal infection, rats were infected with Salmonella enterica, Shigella flexneri, and Escherichia coli. The rats were weighed and their stools cultured. The results showed that the group which had the chitosan encapsulated bacteriophage cocktail did not lose weight after 3 days and had significantly lower group weight changes. Weight loss was significant in the rats that had cefixime administered instead. Positive cultured stools were reduced after 4 days compared to 2 days in the treated group with the chitosan encapsulated bacteriophage cocktail. The chitosan encapsulated bacteriophage cocktail can therefore be effective in the treatment of gastrointestinal infections.

Anti-Microbial Potential of Nano-Emulsion form of Essential Oil Obtained from Aerial Parts of Origanum Vulgare L. as Food Additive.

Purpose: Foodborne diseases are still a serious problem in public health and natural compounds are being widely considered for their potential industrial protective additive in food products. Origanum vulgare L. has been known as an antimicrobial effective herb. This present study was carried out to examine the antimicrobial effect of O. vulgare essential oil nanoemulsion in comparison with conventional emulsion. Methods: The essential oil was obtained by hydrodistillation, analyzed by GC-Mass and formulated as a nanoemulsion to improve water dispersion by high-energy emulsification method. The antimicrobial activity of the prepared formulation was assessed by measuring the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC) and zone of inhibition against some main foodborne pathogen microorganisms. Results: The main component of the oregano essential oil was carvacrol (78%) and the selected nanoemulsion formulation demonstrated low polydispersity (0.11) and mean droplet (72.26 nm) and it was stable even after 30 days of storage. The nanoemulsion form displayed significant activity against the Staphylococcus aureus, Candida albicans and Aspergillus niger with inhibition zones ranging from 8.7-22.3 mm. The MIC of nanoemulsion against the tested bacteria was within the range of 0.156 to 0.312 (mg/mL) and against the tested fungi were in the range of 0.078 to 0.156 (mg/mL). The MBC/MFC of nanoemulsion against the tested microorganisms were in the range of 0.312 to 5 (mg/mL). Conclusion: The study's results demonstrated the possibility of using the nanoemulsion form of oregano essential oil as a food additive to inhibit the growth of some foodborne microorganisms and extending the shelf life of food products.

An eco-friendly and green formulation in lipid nanotechnology for delivery of a hydrophilic agent to the skin in the treatment and management of hyperpigmentation complaints: Arbutin niosome (Arbusome).

The present work designed to improve the skin delivery of arbutin niosome (arbusome) was prepared via an ultrasonic technique. The arbusome formulations were optimized by investigating the effects of the cholesterol:surfactants ratio. To characterize the morphology and solid-state of arbutin in arbusome, differential scanning calorimetry, photon correlation spectroscopy, powder x-ray diffractometer, scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared spectroscopy were utilized. The findings indicated that adding cholesterol incremented the arbusome's particle size. Further studies proved that the zeta potential and the size of nanoparticles can be modulated by the alterations in the ratio of cholesterol: surfactant. When the cholesterol concentration was high in the formulation, the highest entrapment efficiency was found to be approximately 44 %. Solid-state analysis showed that arbutin in the niosome was in the amorphous state. The skin permeation test indicated the greater quantities of the arbutin in skin layers and the receptor chamber for arbusome gel compared to arbutin simple gel. Furthermore, in vitro cytotoxicity test indicated no cytotoxicity for the improved formulation of niosome containing arbutin. The cell viability (HFF cell line) for niosomal formulation of arbutin was reported to be about 86 %. The formulations were examined in terms of skin irritation on Wistar rats, and non-irritancy of arbutin niosomal gels was indicated. The findings of this work discovered that the manufactured arbusome could be utilized as possible nano-vehicle for the arbutin topical delivery and might open new approaches for the treatment of hyperpigmentation complaints.