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.

The effects of Lavandula angustifolia essential oil on analgesic effects and percutaneous absorption of naproxen sodium gel; an in vivo and in vitro study.

The percutaneous bioavailability of naproxen is low and several technologies have been utilized to overcome the problem. Although, some studies have reported the permeation-enhancing properties of natural essential oils, no research has reflected the effectiveness of Lavandula angustifolia essential oil (LAEO) on increasing the percutaneous absorption of naproxen sodium from a topical gel. Therefore, the present study was designed to investigate whether LAEO increased the percutaneous absorption and the analgesic effects of naproxen sodium topical gel. In the present study, naproxen topical gel was formulated using carbopol 940 (a gelling agent) and several vehicles such as PEG 400, ethanol, and water and the properties of gels were measured. Percutaneous absorption-enhancing properties of LAEO were measured too. Based on our data, the essential oil-containing formulation of naproxen represented greater penetration into (222.19 ± 24.87 vs. 107.65 ± 6.38 µg/cm2 ), and also across (22.07 ± 4.42 vs. 13.14 ± 2.87 µg/cm2 ) skin layers compared to the naproxen gel. Additionally, a significant analgesic property was observed in the naproxen topical gel containing 0.5% essential oil during both first and late phases of formalin test, as well as the late phase of tail-flick test. It could be concluded that LAEO significantly enhanced naproxen percutaneous absorption and also its analgesic effects.

Evaluation of cinnamaldehyde mucoadhesive patches on minor recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND & OBJECTIVE: The use of herbal medicines to treat common oral diseases increases rapidly. Recurrent aphthous stomatitis is one of the most common oral mucosal diseases, which has an unclear etiology and could lead to severe pain and dysfunction. Cinnamaldehyde is a major component of cinnamon bark oil. Biological properties of cinnamaldehyde, such as antioxidant, antitumor, antifungal, cytotoxic, and anti-mutational characteristics, have been identified. Considering the prevalence of recurrent aphthous stomatitis and the importance of using herbal resources for treatment, the present study aimed to evaluate the effect of mucosal adhesive patches containing Cinnamaldehyde on minor recurrent aphthous stomatitis lesions. MATERIAL & METHODS: In this randomized, double-blind clinical trial, patients were divided into two groups. The intervention group received three daily mucosal adhesive patches to be used in the morning, afternoon, and night. The control group also did the same with a placebo. To evaluate the healing and determine the diameter of the lesions, patients were clinically examined on days zero, 3, 5, and 7. The VAS scale evaluated pain at baseline and after each meal for seven days. The Fisher's exact test, t-test, Shapiro Wilk test, Friedman test, and the Mann-Whitney test were used to analyze the data using the SPSS 20 software. RESULTS: There was no statistically significant difference in the mean diameter of the inflammatory lesion and pain intensity in the two groups in the baseline (p > 0.05). However, the ulcer size was significantly reduced in the cinnamaldehyde group on the third, fifth, and seventh days of the study. Except for baseline, the mean pain intensity significantly decreased in the cinnamaldehyde group compared to the placebo group (p < 0.05). CONCLUSION: Cinnamaldehyde mucoadhesive patches effectively reduced and improved aphthous lesions and pain intensity in patients and can be considered a treatment for RAS. REGISTRATION NUMBER: IRCT20180312039060N2-First registration date: 20/07/2018. The present study was registered as a retrospective study.

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.

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.

Evaluation of in-situ gel-forming eye drop containing bacteriophage against Pseudomonas aeruginosa keratoconjunctivitis in vivo.

Introduction: Eradication of Pseudomonas aeruginosa has become increasingly difficult due to its remarkable capacity to resist antibiotics. Bacteriophages have been suggested as an alternative treatment for bacterial infections. Methods: In-situ gel-forming eye drop containing phage against P. aeruginosa keratoconjunctivitis was prepared. The Cystoviridae phage was formulated as in-situ gel-forming formulation which is a solution formulation but turns into gel when it contacts the eye. Therapeutic effectiveness of the in-situ gel forming formulation was evaluated by histological examination on day 12 post-infection. Results: The viscosity of selected formulation increased when it was instilled into the eye. The histological results showed edema, abscesses, and destruction of the stromal structure of cornea in groups where no in-situ gel-forming formulation was used. In the group where in-situ gel forming formulation was used, re-epithelialization and normal corneal structure were observed. Conclusion: In-situ gel-forming ophthalmic formulation containing phage can be effective in the treatment of P. aeruginosa keratoconjunctivitis.

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.

Atorvastatin Solid Lipid Nanoparticles as a Promising Approach for Dermal Delivery and an Anti-inflammatory Agent.

In the current research, the main focus was to overcome dermal delivery problems of atorvastatin. To this end, atorvastatin solid lipid nanoparticles (ATR-SLNs) were prepared by ultra-sonication technique. The prepared SLNs had a PDI value of ≤ 0.5, and the particle size of nanoparticles was in the range 71.07 ± 1.72 to 202.07 ± 8.40 nm. It was noticed that, when the concentration of lipid in ATR-SLNs increased, the size of nanoparticles and drug entrapment efficiency were also increased. Results showed that a reduction in the HLB of surfactants used in the preparation of SLN caused an increase in the particle size, zeta potential (better stability), and drug entrapment efficiency. Despite Tween and Span are non-ionic surfactants, SLNs containing these surfactants showed a negative zeta potential, and the absolute zeta potential increased when the concentration of Span 80 was at maximum. DSC thermograms, FTIR spectra, and x-ray diffraction (PXRD) pattern showed good incorporation of ATR in the nanoparticles without any chemical interaction. In vitro skin permeation results showed that SLN containing atorvastatin was capable of enhancing the dermal delivery of atorvastatin where a higher concentration of atorvastatin can be detected in skin layers. This is a hopeful promise which could be developed for clinical studies of the dermal delivery of atorvastatin nanoparticles as an anti-inflammatory agent.

An emerging technology in lipid research for targeting hydrophilic drugs to the skin in the treatment of hyperpigmentation disorders: kojic acid-solid lipid nanoparticles.

Kojic acid (KA) as tyrosinase inhibitor shows insufficient skin penetration and several adverse events due topical administration. KA solid lipid nanoparticles (KA-SLNs) were prepared using high speed homogenisation followed by ultra-probe sonication method for improve its effectiveness.KA-SLNs was optimised by Glyceryl mono-stearate (GMS) and Cholesterol (Chol) as lipid excipients and span 60 (SP 60) and Tween 20 (Tw 20) as co-emulsifiers (particle size 156.97 ± 7.15 nm, encapsulation efficiency 59.02 ± 0.74%, drug loading 14.755 ± 1.63%, polydispersity index (PDI) of 0.388 ± 0.004 and zeta potential (ZP) of -27.67 ± 1.89 mV). Optimum formulation (KA-SLN3 dispersion) was stable at 4 and 25 °C for 3 months. Also, TEM image confirmed these results. The results of XRD, DSC and ATR-FTIR analysis indicated that KA was well encapsulated within the SLNs either in molecularly dispersed state and stabilised in amorphous form and there was no chemical interaction between drug and other ingredients. Controlled release was achieved with this formulation. KA-SLN3 dispersion have more tyrosinase inhibition potency in comparison with pure KA. Also, the results of the ex vivo and in vitro percutaneous absorption show that KA-SLN3 dispersion improved percutaneous delivery of KA as a promising and potential novel topical preparation and might open new avenues for treatment of hyperpigmentation disorders.

Topical gel of Metformin solid lipid nanoparticles: A hopeful promise as a dermal delivery system.

The aim of the present study was to enhance the skin delivery of metformin by making solid lipid nanoparticles containing metformin using the ultra-sonication method. To achieve the optimum skin delivery for metformin, the effects of the ratio of two surfactants (Tween:Span) on nanoparticles properties and their performance were investigated. Photon correlation spectroscopy, scanning electron microscopy (SEM), Powder X-ray Diffractometer (PXRD), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to characterize the solid state of metformin in solid lipid nanoparticles. Generally, the particle size of nanoparticles decreased by the addition of co-emulsifier (Span®60). Results showed that all formulations made by binary mixtures of surfactants had low particle size, low Polydispersity index and high zeta potential. It was interesting to note that the smallest nanoparticles (203.8 ± 15.356) was obtained when the HLB of the binary surfactants (HLB of 11.67) was closer to the HLB of beeswax (HLB of 12) used in the preparation of SLN. It was also found that by decreasing the HLB of the system from 14.9 to 10.06 the zeta potential of SLNs increased from -0.651 ± 0.315 to -6.18 ± 0.438 mV. But, a further reduction in the HLB from 10.06 to 8.45 caused a reduction in the zeta potential from -6.18 to -3.596 ± 0.255. Results showed that the highest entrapment efficiency of 45.98 ± 9.20% was obtained for formulation with larger particle size and with the highest HLB value (HLB 14.9). DSC study showed that metformin in SLN is in an amorphous form. FT-IR spectra of Met-SLN showed that the prominent functional groups existed in the formulations which could be an indication of good entrapment of metformin in a lipid matrix. FT-IR results also ruled out any chemical interaction between the drug and the excipients. The amounts of metformin detected in the skin layers and the receptor chamber at all sampling times were higher for nanogel compared to metformin gel. This is an indication of a better performance of Metformin nanogel ex-vivo and could be developed further for clinical studies.

The design of naproxen solid lipid nanoparticles to target skin layers.

The aim of the current investigation was to produce naproxen solid lipid nanoparticles (Nap-SLNs) by the ultrasonication method to improve its skin permeation and also to investigate the influence of Hydrophilic-lipophilic balance (HLB) changes on nanoparticles properties. The properties of obtained SLNs loaded with naproxen were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). FT-IR was also used to investigate any interaction between naproxen and the excipients used at the molecular level during the preparation of the SLNs. The performance of the formulations was investigated in terms of skin permeation and also the retention of the drug by the skin. It was found that generally, with increasing the lipid concentration, the average particle size and polydispersity index (PDI) of SLNs increased from 94.257±4.852nm to 143.90±2.685nm and from 0.293±0.037 to 0.525±0.038 respectively. The results also showed that a reduction in the HLB resulted in an increase in the PDI, particle size, zeta potential and entrapment efficiency (EE%). DSC showed that the naproxen encapsulated in the SLNs was in its amorphous form. The peaks of prominent functional groups of naproxen were found in the FT-IR spectra of naproxen-SLN, which confirmed the entrapment of naproxen in the lipid matrix. FT-IR results also ruled out any chemical interaction between drug and the chemicals used in the preparation of SLNs. The amount of naproxen detected in the receptor chamber at all the sampling times for the reference formulation (naproxen solution containing all surfactants at pH 7.4) was higher than that of the Nap-SLN8 formulation. Nap-SLN8 showed an increase in the concentration of naproxen in the skin layer with less systemic absorption. This indicates that most of the drug in Nap-SLN8 remains in the skin which can reduce the side effect of systemic absorption of the drug and increases the concentration of the drug at the site of the action.