Nanosized ethosomal dispersions for enhanced transdermal delivery of nebivolol using intradermal/transfollicular sustained reservoir: in vitro evaluation, confocal laser scanning microscopy, and in vivo pharmacokinetic studies.

Nebivolol (NBV), a BCS class II anti-hypertensive drug, suffers from limited solubility and oral bioavailability. Nanosized ethosomes were adopted as an approach to solubilize and deliver NBV transdermally, as a substitute to oral route. Ethosomal dispersions were prepared employing thin film hydration method. Formulation variables were adjusted to obtain entrapment efficiency; EE > 50%, particle size; PS < 100 nm, zeta potential; ZP > ±25 mV, and polydispersity index; PDI < 0.5. The optimized ethosomal dispersion (OED) showed accepted EE 86.46 ± 0.15%, PS 73.50 ± 0.08 nm, ZP 33.75 ± 1.20 mV, and PDI 0.31 ± 0.07. It also showed enhanced cumulative amount of NBV permeated at 8 h (Q8) 71.26 ± 1.46% and 24 h (Q24) 98.18 ± 1.02%. TEM images denoted spherical vesicles with light colored lipid bi-layer and dark core. Confocal laser scanning microscopy showed deeply localized intradermal and transfollicular permeation of the fluorolabelled OED (FL-OED). Nanosized FL-OED (<100 nm) can permeate through hair follicles creating a drug reservoir for enhanced systemic absorption. OED formulated into transdermal patch (OED-TP1) exhibited accepted physicochemical properties including; thickness 0.14 ± 0.01 mm, folding endurance 151 ± 0.07, surface pH 5.80 ± 0.15, drug content 98.64 ± 2.01%, mucoadhesion 8534 ± 0.03, Q8 87.61 ± 0.11%, and Q24 99.22 ± 0.24%. In vivo pharmacokinetic studies showed significantly enhanced bioavailability of OED-TP1 by 7.9 folds compared to oral Nevilob® tablets (p = 0.0002). It could be concluded that OED-TP1 can be a promising lipid nanocarrier TDDS for NBV and an efficacious alternative route of administration for hypertensive patients suffering from dysphagia.

Ethosomes loaded with lipophilic drugs, as NBV, can have two possible pathways of permeation through the skin; intradermal and transfollicular.Nanosized ethosomes (< 100 nm) can produce efficient intradermal and transfollicular reservoirs for sustained drug delivery.The formulated transdermal patch loaded with the optimized ethosomal dispersion (OED) showed enhanced bioavailability by 7.9 folds compared to Nevilob® oral tablets.

Topical delivery of extracted curcumin as curcumin loaded spanlastics anti-aging gel: Optimization using experimental design and ex-vivo evaluation.

Objective: This study aimed to extract and separate the organic coloring agent known as Curcumin from the rhizomes of Curcuma longa, and then to create Spanlastics that were loaded with curcumin using the ethanol injection technique. The optimized Spanlastic dispersions were then incorporated into a gel preparation for topical anti-aging use. The Spanlastic dispersions were analyzed for particle size, zeta potential, drug loading efficiency, and in vitro release profile. Furthermore, the rheological properties of the gel preparation were assessed, and a skin penetration study was conducted using confocal microscopy. Methods: Twelve different Curcumin-loaded Spanlastic dispersions using the ethanol injection method with Span® 60 as a surfactant and Tween® 80 as an edge activator in varying ratios. The dispersions were then subjected to various tests, such as particle size analysis, zeta potential measurement, drug entrapment efficiency assessment, and in vitro release profiling. The optimized formula was selected using Design-Expert® software version 13, then used to create a gel preparation, which utilized 2% HPMC E50 as a gelling polymer. The gel was evaluated for its rheological properties and analyzed using confocal microscopy. Additionally, Raman analysis was performed to ensure that the polymers used in the gel were compatible with the drug substance. Results: F5 formula, (that contains 10 mg Curcumin, and mixture 5 of span-tween mixtures that consist of 120 mg Span® 60 with 80 mg Tween® 80) was selected as the optimized formula with a desirability produced by Design Expert® software equal to 0.761, based on its particle size (212.8 ± 4.76), zeta potential (-29.4 ± 2.11), drug loading efficiency (99.788 ± 1.34), and in vitro release profile evaluations at Q 6hr equal to almost 100 %. Statistical significance (P < 0.05) was obtained using one-way ANOVA. Then F5 was used to formulate HPMC E50 gel-based preparations. The gel formula that was created and analyzed using Raman spectroscopy demonstrated no signs of incompatibility between the Curcumin and the polymers that were utilized.The confocal spectroscopy found that the anti-aging gel preparation showed promising results in terms of skin penetration. Also, images revealed that the gel could penetrate the layers of the skin (reached a depth of about 112.5 µm), where it could potentially target and reduce the appearance of fine lines and wrinkles. The gel also appeared to be well-tolerated by the skin, with no signs of irritation or inflammation observed in the images. Conclusion: The obtained results successfully confirmed the potential of the promising (F5) formula to produce sustained release action and its ability to be incorporated into 2% HPMC E50 anti-aging gel. The confocal microscopy study suggested that the anti-aging gel had the potential to be an effective and safe topical treatment for aging skin.

Sucrose acetate isobutyrate (SAIB) and glyceryl monooleate (GMO) hybrid nanoparticles for bioavailability enhancement of rivaroxaban: an optimization study.

This study aims to improve the RXB bioavailability using hybrid nanoparticles. A modified melt dispersion technique created different formulas with varying GMO-SAIB: RXB and GMO: SAIB ratios, with fixed GMO-SAIB: poloxamer 407 ratios. The PS, PDI, ZP, and EE were measured to determine the optimal formula, which was selected using Design-Expert™ software. The optimized formula was lyophilized and tested for PS, PDI, ZP, and EE. The chosen lyophilized formula (L4) was characterized using FTIR, DSC, PXRD, dissolution studies, and pharmacokinetics studies. The study found correlations between variables and identified how GMO-SAIB concentration affects drug encapsulation. The dissolution parameters were calculated, including % Q5 and % DE). The % Q5 values were 68.4 ± 1.7% and 89.7 ± 3.6% for Xarelto and L4 tablets, respectively. The % DE values were 89.7 ± 0.4% and 97.5 ± 2.1% for Xarelto and L4 tablets, respectively. The AUC values were 2117.0 ng.h/mL (±77.3) and 3919.4 ng.h/mL (±134.8) for Xarelto and L4 tablets, respectively. The Cmax values were 241.3 ng/mL (±21.0) and 521.5 ng/mL (±91.5) for Xarelto and L4 tablets, respectively. In conclusion, the study found that using GMO-SAIB as co-formers effectively enhanced the bioavailability of RXB. The authors recommend using the hybrid nanoparticles technique and suggest further research to enhance its effectiveness for drug delivery.

State-of-the-Art Review of Advanced Electrospun Nanofiber Composites for Enhanced Wound Healing.

Wound healing is a complex biological process with four main phases: hemostasis, inflammation, proliferation, and remodeling. Current treatments such as cotton and gauze may delay the wound healing process which gives a demand for more innovative treatments. Nanofibers are nanoparticles that resemble the extracellular matrix of the skin and have a large specific surface area, high porosity, good mechanical properties, controllable morphology, and size. Nanofibers are generated by electrospinning method that utilizes high electric force. Electrospinning device composed of high voltage power source, syringe that contains polymer solution, needle, and collector to collect nanofibers. Many polymers can be used in nanofiber that can be from natural or from synthetic origin. As such, electrospun nanofibers are potential scaffolds for wound healing applications. This review discusses the advanced electrospun nanofiber morphologies used in wound healing that is prepared by modified electrospinning techniques.

Efficacy of pomegranate extract loaded solid lipid nanoparticles transdermal emulgel against Ehrlich ascites carcinoma.

The purpose of this work was to incorporate an optimized pomegranate extract loaded solid lipid nanoparticles (PE-SLNs) formula in a transdermal emulgel to evaluate its anticancer effect. The prepared emulgel formulae were evaluated for their physicochemical properties. An ex vivo permeation study was done through mouse skin and the kinetic parameters were determined. Kinetic data showed that the ex vivo permeation of PE from SLNs transdermal emulgel through mouse skin followed non-Fickian diffusion transport. Further, in vivo study was done by applying the optimized PE-SLNs transdermal emulgel on mice skin bearing a solid form of Ehrlich ascites carcinoma (EAC) as well as free PE, control, placebo, and standard groups for comparison. In addition, histopathological examinations of the samples obtained from the EAC mice model were performed. The results proved that application of the selected PE-SLNs emulgel formulation on the mice skin bearing solid tumor revealed statistically significant anticancer effects.

Clove Oil Endorsed Transdermal Flux of Dronedarone Hydrochloride Loaded Bilosomal Nanogel: Factorial Design, In vitro Evaluation and Ex vivo Permeation.

The goal of this study was to develop a bilosomal gel formulation to enhance transdermal permeability of dronedarone hyrdrochloride (DRN) which suffers from poor oral absorption and limited bioavailability. To overcome this obstacle, bilosomes were successfully prepared using 23 full-factorial design. Span®40, cholesterol, sodium deoxycholate (bile salt), clove oil (permeability enhancer), and either Tween® 60 or Tween® 80 (edge activator) were used in bilosome preparation by ethanol injection method. In this design, independent variables were X1, edge activator type; X2, edge activator amount (mg); and X3, permeability enhancer concentration (% w/v). Optimal formula (B2) of the highest desirability of (0.776) demonstrated minimum vesicle size (VS) of 312.4 ± 24.42 nm, maximum absolute value of zeta potential (ZP) - 36.17 ± 2.57 mV, maximum entrapment efficiency (EE %) of 80.95 ± 3.01%, maximum deformability Index (DI) of 8.24 ± 1.26 g and maximum drug flux after 12 h (J12) of 21.23 ± 1.54 µg/cm2 h upon ex vivo permeation study. After 12 h, 70.29 ± 6.46% of DRN was released from B2. TEM identification of B2 showed spherical shaped nanosized vesicles which were physically stable for 3 months at different temperatures. B2 was incorporated into carboxymethylcellulose gel base for easiness of dermal application. B2 gel demonstrated good physical properties, non-Newtonian psuedoplastic flow, and enhanced release (57.0 ± 8.68% of DRN compared to only 13.3 ± 1.2% released from drug suspension after 12 h) and enhanced skin permeation.

Formulation and evaluation of niosomal vesicles containing ondansetron HCL for trans-mucosal nasal drug delivery.

Ondansetron HCl is a (5-HT3) serotonin receptor antagonist, used as anti-emetic drug in combination with anticancer agents. Conventional dosage forms have poor bioavailability and patient compliance. These problems can be reduced by the use of nasal niosomal thermo-reversible in situ gelling system. Niosomes were formulated using various surfactants (Span 60, Span 80, Tween 20, and Tween 80) in different ratios using the thin-film hydration technique. Niosomes were evaluated for particle size, zeta potential, transmission electron microscopy (TEM) imaging, drug entrapment efficiency, and in vitro drug release. Niosomes prepared using Span 60 and cholesterol in the ratio 1:1 (F5) showed higher entrapment efficiency (76.13 ± 1.2%) and in vitro drug release (91.76%) after 12 h was optimized. The optimized niosomes were developed into thermo-reversible in situ gel, composed of Poloxamer 407 and sodium carboxymethyl cellulose, prepared by cold method technique. Compatibility study (FTIR, DSC) was made for drugs and excipients that showed no significant interaction. The gel formulation G5 showed the most suitable gelation temperature (31 °C), viscosity (1250 mpoise), bioadhesion force (5860 ± 28 dyne/cm2), and in vitro drug release (70.6%) after 12 h. Comparative in vivo pharmacokinetic study on rabbits showed a sustained release and higher relative bioavailability of the prepared nasal in situ gel compared to similar dose of oral tablets (202.4%) which make ondansetron HCl niosomal nasal thermo-sensitive in situ gel a more convenient dosage form for the administration of ondansetron HCl than oral tablets.

Eco-friendly synthesis of functionalized chitosan-based nanoantibiotic system for potential delivery of linezolid as antimicrobial agents.

To obtain a healthy human being with beneficial microflora against different pathogenic infections, classical antibiotics with nanosized biomaterials were used to inhibit the growth of bacterium by their potent synergistic effect. Hence, this study planned to load an oxazolidinone antibiotic named linezolid (LD) onto functionalized chitosan (CN) with 3, 5- dinitrosalyslic acid (DA) via microwave synthesis without harsh condition. The exploring synergistic effect of linezolid (LD) with CN/DA controllable nanostructure was compact efflux-mediated methicillin-resistant Staphylococcus aureus (MRSA) burden and other selected bactericide Gram-positive ((S. aureus), Gram-negative (E. coli), Fungi (C. albicans), Yeast (A. niger), and E. faecalis. The obtained results showed that LD was incorporated into both the internal and external surface of the aggregated CN/DA nanosystem with an average diameter of 150 nm ± 4 hints of the drug loading. Owing to the nature of functionalized CN, the release efficiency attains 98.4% within 100 min. The designed LD@CN/DA exhibited inhibition zone 54 mm, 59 mm, 69 mm, 54 mm, 57 mm, and 24 mm against the tested microbes respectively rather than individual LD. The major target of the current research is achieved by using LD@CN/DA as a nanoantibiotic system that has exceptional consistently active against multi-resistant pathogens, in between MRSA which resist LD. Also, cell viability was performed even after three days of direct cell culture on the surface of the designed nanoantibiotic. The mechanism of microbial inhibition was correlated and rationalized to different charges and the presence of oxygen species against microbial infections. Our findings provide a deep explanation about nanostructured antibiotics design with enhanced potentially pathogen-specific activity.

Dual-purpose vardenafil hydrochloride/dapoxetine hydrochloride orodispersible tablets: in vitro formulation/evaluation, stability study and in vivo comparative pharmacokinetic study in healthy human subjects.

Erectile dysfunction (ED) is the most important disorder after premature ejaculation for sexual activity in men. Vardenafil hydrochloride (VH) is an oral therapy for the treatment of erectile dysfunction. VH oral disintegrating tablets (ODTs) have been prepared by freeze drying technique to improve its dissolution profile and the overall clinical performance. Dapoxetine hydrochloride (DH) was added to the best three formulae of the prepared VH ODTs to treat premature ejaculation. All the ODTs formulae were evaluated for weight variation, friability, drug content, in vitro disintegration time, wetting time, and the dissolution study. Gelatin as a matrix former with N-methylpyrrolidone as a solubilizer in VH/DH ODTs improved the dissolution rate and extent of release of VH and DH with 100% of drug being dissolved after 15 min. In vivo study results from six healthy male volunteers showed shorter Tmax of VH from VH/DH ODT of 0.583 ± 0.129 h and shorter Tmax of DH from VH/DH ODT of 0.625 ± 0.137 h and showed AUC0-12 of VH from VH/DH ODT of 39.234 ± 10.932 ng/ml h1 and AUC0-12 of DH from VH/DH ODT of 531.681 ± 129.544 ng/ml h1, with relative bioavailability values of 100.9 and 85%, respectively, compared to (Levitra®) and (Priligy®).

Non-ionic surfactant based vesicular drug delivery system for topical delivery of caffeine for treatment of cellulite: design, formulation, characterization, histological anti-cellulite activity, and pharmacokinetic evaluation.

Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destock® was evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS-MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII > FXIV > Cellu Destock® > FVII + Iontophoresis > FXIV + Iontophoresis. Pharmacokinetic results of caffeine in plasma revealed that Cmax, Tmax, and AUC0-12h decreased in the following order: FXIV > FVII > Cellu Destock®. These results conclude that incorporation of caffeine niosomal dispersion into gel matrix with penetration enhancers and iontophoresis resulted in improvement in penetration of caffeine through the skin into the underlying fatty layer in treatment of cellulite.

Formulation and optimization of surfactant-modified chitosan nanoparticles loaded with cefdinir for novel topical drug delivery: Elevating wound healing efficacy with enhanced antibacterial properties.

Burn wounds remain a significant global health concern, frequently exacerbated by bacterial infections that hinder healing and raise morbidity rates. Cefdinir, a third-generation cephalosporin antibiotic, is used to treat various conditions, but it has limitations such as low water solubility, limited bioavailability, and a short biological half-life. This study aimed to fabricate and optimize novel surfactant-based Cefdinir-loaded chitosan nanoparticles (CFD-CSNPs) for enhancing topical CFD delivery and efficacy in burn healing. Box-Behnken Design (BBD) was employed to develop optimized CFD-CSNPs using Design Expert® software, where the independent factors were chitosan concentration, chitosan: sodium tripolyphosphate ratio, pH, and surfactant type. Particle size PS, zeta potential ZP, Polydispersity index PDI, and entrapment efficiency EE% were evaluated as dependent factors. CFD-CSNPs were produced using the ionic gelation method. The optimized formula was determined and then examined for further in vitro and in vivo assessments. The optimized CFD-CSNPs exhibited acceptable PS, PDI, and ZP values. The EE% of CFD from CSNPs reached 57.89 % ± 1.66. TEM analysis revealed spherical morphology. In vitro release studies demonstrated a biphasic release profile up to (75.5 % ± 3.8) over 48 hrs. The optimized CFD-CSNPs showed improved antimicrobial efficacy against the tested microorganisms, exhibiting superior performance for both biofilm prevention and eradication. Enhanced wound healing activity was achieved by the optimized CFD-CSNPs in both in vitro and in vivo studies as confirmed by scratch wound assay and skin burn mice model. The current study advocates the efficacy of the innovative topical application of CFD-CSNPs for wound healing purposes and treatment of wound infections.

Comparative Pharmacokinetic Study of Standard Astaxanthin and its Micellar Formulation in Healthy Male Volunteers.

BACKGROUND AND OBJECTIVE: Astaxanthin is a naturally occurring carotenoid with high anti-oxidant properties, but it is a very lipophilic compound with low oral bioavailability. This study was conducted to compare the pharmacokinetic parameters of a novel astaxanthin preparation based on micellar solubilization technology, NovaSOL® 400-mg capsules (Test product), and those of astaxanthin 400-mg capsules (reference product), after single oral dose administration to healthy male adults. METHODS: A single oral dose (400 mg equivalent to 8 mg astaxanthin) of test and reference astaxanthin were administered with 240 mL of water to 12 volunteers according to crossover design, in two phases, with a washout period of 1 week in between. Blood samples were collected at hourly intervals for the first 12 h, then at 24.0, 48.0, and 72.0 h after administration. Aliquots of plasma were centrifuged and the clear supernatant was injected into the high performance liquid chromatography-diode array detection (HPLC-DAD) system. Plasma concentration of astaxanthin versus time profiles were constructed, and the primary pharmacokinetic parameters, maximum concentration (Cmax), area under concentration time curve from time of administration (0) to time (t) [AUC0-t] or to infinity ∞, [AUC0-∞],  half-life (T½) and time to reach Cmax (Tmax) were calculated. RESULTS: The test micellar astaxanthin reached a Cmax of 7.21 µg/ml after 3.67 h compared to only 3.86 µg/ml after 8.5 h for the reference native astaxanthin. CONCLUSION: Micellar formulation of astaxanthin is capable of producing a high concentration of astaxanthin in plasma in a shorter time, thereby expected to provide faster potential therapeutic efficacy.

Nanocomposite alginate hydrogel loaded with propranolol hydrochloride kolliphor® based cerosomes as a repurposed platform for Methicillin-Resistant Staphylococcus aureus-(MRSA)-induced skin infection; in-vitro, ex-vivo, in-silico, and in-vivo evaluation.

Nanocomposite alginate hydrogel containing Propranolol hydrochloride (PNL) cerosomes (CERs) was prepared as a repurposed remedy for topical skin Methicillin-Resistant Staphylococcus aureus (MRSA) infection. CERs were formed via an ethanol injection technique using different ceramides, Kolliphores® as a surfactant, and Didodecyldimethylammonium bromide (DDAB) as a positive charge inducer. CERs were optimized utilizing 13. 22 mixed-factorial design employing Design-Expert® software, the assessed responses were entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimum CER, composed of 5 mg DDAB, ceramide VI, and Kolliphor® RH40 showed tubular vesicles with EE% of 92.91 ± 0.98%, PS of 388.75 ± 18.99 nm, PDI of 0.363 ± 0.01, and ZP of 30.36 ± 0.69 mV. Also, it remained stable for 90 days and manifested great mucoadhesive aspects. The optimum CER was incorporated into calcium alginate to prepare nanocomposite hydrogel. The ex-vivo evaluation illustrated that PNL was permeated in a more prolonged pattern from PNL-loaded CERs nanocomposite related to PNL-composite, optimum CER, and PNL solution. Confocal laser scanning microscopy revealed a perfect accumulation of fluorescein-labeled CERs in the skin. The in-silico investigation illustrated that the PNL was stable when mixed with other ingredients in the CERs and confirmed that PNL is a promising candidate for curing MRSA. Moreover, the PNL-loaded CERs nanocomposite revealed superiority over the PNL solution in inhibiting biofilm formation and eradication. The PNL-loaded CERs nanocomposite showed superiority over the PNL-composite for treating MRSA infection in the in-vivo mice model. Histopathological studies revealed the safety of the tested formulations. In conclusion, PNL-loaded CERs nanocomposite provided a promising, safe cure for MRSA bacterial skin infection.

Enhancing cellular affinity for skin disorders: Electrospun polyurethane/collagen nanofiber mats coated with phytoceramides.

Although the use of thermoplastic polyurethane (Tpu) nanofiber mats as wound dressings is of great interest due to their mechanical properties, they are hindered by their poor wettability and bioavailability. In this study, we aimed to improve the cellular affinity of Tpu nanofiber mats for skin disorders by incorporating extracted collagen (Col) from tendons and physically mixed with a layer of phytoceramides (Phyto) to produce TpuCol@X-Phyto mats in which the weight % of Phyto relatively to the weight of the solution was X = 0.5, 1.0, or 1.5 wt% via facile electrospinning approach. The collective observations strongly indicate the successful incorporation and retention of Phyto within the TpuCol architecture. An increase in the Phyto concentration decreased the water contact angle from 69.4° ± 3.47° to 57.9° ± 2.89°, demonstrating improvement in the hydrophilicity of Tpu and binary blend TpuCol nanofiber mats. The mechanical property of 1.0 wt% Phyto aligns with practical requirements owing to the presence of two hydroxyl groups and the amide linkage likely contributing to various hydrogen bonds, providing mechanical strength to the channel structure and a degree of rigidity essential for transmitting mechanical stress. The proliferation of human skin fibroblast (HSF) peaked significantly 100 % with TpuCol@X-Phyto mats coated for X =1.0 and 1.5 wt% of Phyto. Electrospun scaffolds with the highest Phyto content have shown the lowest degree of hemolysis, demonstrating the high level of compatibility between them and blood. The TpuCol@1.5Phyto mat also demonstrated higher efficacy in antibacterial and antioxidant activities, achieving a rate of DPPH radical scavenging of 83.3 % for this latter property. The most notable wound closure among all tested formulations was attributed to higher Phyto. Thus, the developed TpuCol@1.5Phyto nanofiber formula exhibited enhanced healing in an in vitro epidermal model.

Resolving acne with optimized adapalene microspongeal gel, in vivo and clinical evaluations.

In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 33. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.

Formulation, optimization and evaluation of ocular gel containing nebivolol Hcl-loaded ultradeformable spanlastics nanovesicles: In vitro and in vivo studies.

The study aims to improve the ocular delivery of Nebivolol HCL (NBV) belonging to the Biopharmaceutics classification system (BCSII) by using spanlastic nanovesicles (SNVs) for ophthalmic delivery and incorporating them into hydroxypropyl methylcellulose gel with ketorolac tromethamine (KET) as an anti-inflammatory to improve glaucoma complications like Conjunctivitis. SNVs were prepared by ethanol injection technique using span (60) as a surfactant and labrasol as an edge activator (EA). The impact of formulation factors on SNVs properties was investigated using a Box-Behnken design. In vitro evaluations showed that the formulations (F1, F4, and F14), containing Span 60 and labrasol as EA (25%, 50%, and 25%), exhibited high EE% with low PS and high ZP and DI. Additionally, 61.72 ± 0.77%, 58.97 ± 1.44%, and 56.20 ± 2.32% of the NBV amount were released from F1, F4, and F14 after 5 h, compared to 93.94 ± 1.21% released from drug suspension. The selected formula (G1), containing F1 in combination with KET and 2% w/w HPMC, exhibited 76.36 ± 0.90% drug release after 12 h. Ex vivo Confocal laser scanning revealed a high penetration of NBV-SNVs gel that ascertained the results of the in-vitro study. In vivo studies showed a significant decrease in glaucoma compared to drug suspension, and histopathological studies showed improvement in glaucomatous eye retinal atrophy. G1 is considered a promising approach to improving ocular permeability, absorption, and anti-inflammatory activity, providing a safer alternative to current regimens.

Chitosan decorated oleosomes loaded propranolol hydrochloride hydrogel repurposed for Candida albicans-vaginal infection.

Aim: Our investigation aims to estimate the antifungal effect of propranolol hydrochloride (PNL). Methods: Oleosomes (OLs) were fabricated by thin-film hydration and evaluated for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and amount of drug released after 6 h Q6h (%). Results: The optimal OL showed a rounded shape with optimum characteristics. The ex-vivo permeation and confocal laser scanning microscopy verified the prolonged release and well deposition of PNL-loaded OLs-gel. The in-silico assessment demonstrated the good stability of PNL with OLs' ingredients. In vivo evaluations for PNL-loaded OLs-gel showed a good antifungal impact against Candida albicans with good safety. Conclusion: This work highlights the potential of PNL-loaded OLs-gel as a potential treatment for candida vaginal infection.

[Box: see text].

Lyophilized Nasal Inserts of Atomoxetine HCl Solid Lipid Nanoparticles for Brain Targeting as a Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): A Pharmacokinetics Study on Rats.

The study aims to investigate the ability of lyophilized nasal inserts of nanosized atomoxetine HCl solid lipid nanoparticles (ATM-SLNs) to transport atomoxetine (ATM) directly to the brain and overcome the first-pass metabolism. In this case, 16 formulae of (ATM-SLNs) were prepared using hot melt emulsification, stirring and ultrasonication method technique. A full factorial design was established with 24 trials by optimization of four variables; lipid type (Compritol 888 ATO or stearic acid) (X1), lipid to drug ratio [(1:2) or (2:1)] (X2), span 60: Pluronic f127 ratio [(1:3) or (3:1)] (X3) and probe sonication time (five or ten minutes) (X4). The prepared SLNs were characterized for entrapment efficiency (EE%), in-vitro drug release after 30 min (Q30min), particle size (PS), zeta potential (ZP) and polydispersity index (PDI). Design Expert® software was used to select the optimum two formulae. The morphological examination for the optimum two formulae was carried out using a transmission electron microscope (TEM). Furthermore, eight lyophilized nasal inserts were prepared by using a 23 full factorial design by optimization of three variables: type of (ATM-SLNs) formula (X1), type of polymer (NOVEON AA1 or HPMC K100m) (X2) and concentration of polymer (X3). They were evaluated for nasal inserts' physicochemical properties. The two optimum inserts were selected by Design Expert® software. The two optimum insets with the highest desirability values were (S4 and S8). They were subjected to DSC thermal stability study and in-vivo study on rats. They were compared with atomoxetine oral solution, atomoxetine (3 mg/kg, intraperitoneal injection) and the pure atomoxetine solution loaded in lyophilized insert. (ATM-SLNs) showed EE% range of (41.14 mg ± 1.8% to 90.6 mg ± 2.8%), (Q30min%) of (27.11 ± 5.9% to 91.08 ± 0.15%), ZP of (-8.52 ± 0.75 to -28.4 ± 0.212% mV), PS of (320.9 ± 110.81% nm to 936.7 ± 229.6% nm) and PDI of (0.222 ± 0.132% to 0.658 ± 0.03%). Additionally, the two optimum (ATM-SLNs) formulae chosen, i.e., F7 and F9 showed spherical morphology. Nasal inserts had assay of drug content of (82.5 ± 2.5% to 103.94 ± 3.94%), Q15min% of (89.9 ± 6.4% to 100%) and Muco-adhesion strength of (3510.5 ± 140.21 to 9319.5 ± 39.425). DSC results of S4 and S8 showed compatibility of (ATM) with the other excipients. S8 and S4 also showed higher trans-nasal permeation to the brain with brain targeting efficiency of (211.3% and 177.42%, respectively) and drug transport percentages of (52.7% and 43.64%, respectively). To conclude, lyophilized nasal inserts of (ATM-SLNs) enhanced (ATM) trans-nasal drug targeting permeation and brain targeting efficiency.

Unroasted Green Coffee Extract-Loaded Solid Lipid Nanoparticles for Enhancing Intestinal Permeation.

Green coffee bean extract (GCBE) provides diversified health benefits. However, its reported low bioavailability impeded its utilization in various applications. In this study, GCBE-loaded solid lipid nanoparticles (SLNs) were prepared to improve the bioavailability through enhanced intestinal absorption of GCBE. During the preparation of promising GCBE-loaded SLNs, the lipid concentration, surfactant concentration, and co-surfactant amount are crucial that were optimized using the Box-Behnken design, while particle size, polydispersity index (PDI), ζ-potential, entrapment efficiency, and cumulative drug release were the measured responses. GCBE-SLNs were successfully developed by a high shear homogenization technique using geleol as a solid lipid, tween 80 as a surfactant, and propylene glycol as Co-SAA. The optimized SLNs contained 5.8% geleol, 5.9% tween 80, and 80.4 mg PG resulting in a small particle size of 235.7 ± 12.5 nm, reasonably acceptable PDI of 0.417 ± 0.023, and ζ-potential of -15 ± 0.14 mV, with a high entrapment efficiency of 58.3 ± 0.85% and cumulative release of 7575 ± 0.78%. Furthermore, the performance of the optimized GCBE-SLN was evaluated using an ex vivo everted sac model where the intestinal permeation of GCBE was improved due to nanoencapsulation using SLN. Consequently, the results enlightened the auspicious potential of exploiting oral GCBE-SLNs for boosting intestinal absorption of chlorogenic acid.

Fabrication and characterization of anti-rosacea 3D nanofibrous customized sheet masks as a novel scaffold for repurposed use of spironolactone with pre-clinical studies.

The repurposed oral use of spironolactone (SP) as an anti-rosacea drug faces many challenges that hinder its efficacy and compliance. In this study, a topically applied nanofibers (NFs) scaffold was evaluated as a promising nanocarrier that enhances SP activity and avoids the friction routine that exaggerates rosacea patients' inflamed, sensitive skin. SP-loaded poly-vinylpyrrolidone (40% PVP) nanofibers (SP-PVP NFs) were electrospun. Scanning electron microscopy showed that SP-PVP NFs have a smooth homogenous surface with a diameter of about 426.60 nm. Wettability, solid state, and mechanical properties of NFs were evaluated. Encapsulation efficiency and drug loading were 96.34% ± 1.20 and 11.89% ± 0.15, respectively. The in vitro release study showed a higher amount of SP released over pure SP with a controlled release pattern. Ex vivo results showed that the permeated amount of SP from SP-PVP NFs sheets was 4.1 times greater than that of pure SP gel. A higher percentage of SP was retained in different skin layers. Moreover, the in vivo anti-rosacea efficacy of SP-PVP NFs using croton oil challenge showed a significant reduction in erythema score compared to the pure SP. The stability and safety of NFs mats were proved, indicating that SP-PVP NFs are promising carriers of SP.