The Enterococcus secretome inhibits the growth of vancomycin-resistant Enterococcus faecalis V853 with their antiproliferative properties and nanoencapsulation effects.

In our study, the secretome of the clinical isolate Enterococcus faecalis HY7 displayed antibacterial activity against the vancomycin-resistant Enterococcus faecalis V853. These bacteriocin-like substances showed thermal stability at a wide range of temperatures up to 121 °C, while proteinase K treatment resulted in a total loss of their activity. PCR-based screening for bacteriocin biosynthetic genes revealed that Enterococcus faecalis HY7 harbored multiple enterocin-producing genes, including ent A, avc A, and as-48. The production kinetics demonstrated the highest levels of bacteriocins production at 16 h, whereas the activity was diminished after 32 h of microbial growth. Notably, the partially purified bacteriocins exhibited anti-proliferative activity on the colon cancer cells, Caco2, with an IC50 value of 172.8 µg/mL. Remarkably, the nanoencapsulation of our bacteriocins in liposome showed a fourfold increase in its anti-vancomycin-resistant Enterococcus activity, which is the first report of liposome encapsulation with anti-vancomycin resistant Enterococcus bacteriocin.

Dexibuprofen enteric film-coated tablets: design, characterization and pharmacokinetic analysis in human volunteers.

OBJECTIVE: This study aimed to develop a stable and scalable enteric film-coated tablet for the gastric irritant dexibuprofen. METHODS: Utilizing direct compression with super-disintegration (crospovidone), the optimal core batches were coated with Opadry white seal coat and enterically coated with Eudragit®L100 with pigment (Talc), demonstrating a 12% weight increase; release and integrity were assessed using specific pH buffers and SEM, with stability testing confirming a six-month shelf life at 40 °C and 75% RH. RESULTS: The optimized formulation achieved 99.87% release in phosphate buffer within 60 min, maintained integrity for 120 min in acidic conditions, and exhibited superior bioavailability compared to Innovifen with relative bioavailability ≈of 121% and elevated Cmax (18.35 µg/ml compared to 11.1 µg/ml). CONCLUSION: These results highlight the potential of this formulation to enhance patient safety and efficacy through delayed enteric technology and fast intestinal release.

Dinebra retroflexa Herbal Phytotherapy: A Simulation Study Based on Bleomycin-Induced Pulmonary Fibrosis Retraction Potential in Swiss Albino Rats.

Background and Objectives: Fibrotic lung disease is one of the main complications of many medical conditions. Therefore, the use of anti-fibrotic agents may provide a chance to prevent, or at least modify, such complication. The aim of this study was to evaluate the protective pulmonary anti-fibrotic and anti-inflammatory effects of Dinebra retroflexa. Materials and methods: Dinebra retroflexa methanolic extract and its synthesized silver nanoparticles were tested on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/5 mL/kg-Saline) as a supposed model for induced lung fibrosis. The weed evaluation was performed by intratracheal instillation of Dinebra retroflexa methanolic extract and its silver nanoparticles (35 mg/100 mL/kg-DMSO, single dose). Results: The results showed that both Dinebra retroflexa methanolic extract and its silver nanoparticles had a significant pulmonary fibrosis retraction potential, with Ashcroft scores of three and one, respectively, and degrees of collagen deposition reduction of 33.8 and 46.1%, respectively. High-resolution UHPLC/Q-TOF-MS/MS metabolic profiling and colorimetrically polyphenolic quantification were performed for further confirmation and explanation of the represented effects. Such activity was believed to be due to the tentative identification of twenty-seven flavonoids and one phenolic acid along with a phenolic content of 57.8 mg/gm (gallic acid equivalent) and flavonoid content of 22.5 mg/gm (quercetin equivalent). Conclusion: Dinebra retroflexa may be considered as a promising anti-fibrotic agent for people at high risk of complicated lung fibrosis. The results proved that further clinical trials would be recommended to confirm the proposed findings.

In vitro and in vivo performance modelling and optimisation of different dry powder inhalers: A complementary study of neural networks, genetic algorithms and decision trees.

INTRODUCTION: Aerosol delivery from DPIs could be affected by different factors. This study aimed to evaluate and predict the effects of different factors on drug delivery from DPIs. METHODS: Modelling and optimisation for both in vitro and in vivo data of different DPIs (Diskus, Turbohaler and Aerolizer) were carried out using neural networks associated with genetic algorithms and the results are confirmed using a decision tree (DT) and random forest regressor (RFR). All variables (the type of DPI, inhalation flow, inhalation volume, number of inhalations and type of subject) were coded as numbers before using them in the modelling study. RESULTS: The analysis of the in vitro model showed that Turbohaler had the highest emitted dose compared with the Diskus and the Aerolizer. Increasing flow resulted in a gradual increase in the emitted dose. Little differences between the inhalation volumes 2 and 4 litres were shown at fast inhalation flow, and interestingly two inhalations showed somewhat higher emitted doses than one-inhalation mode with Turbohaler and Diskus at slow inhalation flow. Regarding the in vivo model, the percent of drug delivered to the lung was highly increased with Turbohaler and Diskus in healthy subjects where continuous contour lines were observed. The Turbohaler showed increased lung bioavailability with the two-inhalation modes, the Diskus showed a nearly constant level at both one and two inhalations at slow inhalation. The Turbohaler and Aerolizer showed little increasing effect moving from one to two inhalations at slow inhalation. CONCLUSIONS: Modelling of the input data showed a good differentiating and prediction power for both in vitro and in vivo models. The results of the modelling refer to the high efficacy of Diskus followed by Turbohaler for delivering aerosol. With two inhalations, the three DPIs showed an increase in the percent of drug excreted at slow inhalations.

Surface modified niosomes of olanzapine for brain targeting via nasal route; preparation, optimization, and in vivo evaluation.

Olanzapine (OL) is an atypical antipsychotic drug which suffers from an extensive hepatic metabolism and poor bioavailability. In addition, it has low brain permeability due to efflux by P-glycoproteins. In the current investigation, surface modified niosomes containing OL were prepared for brain targeting of the drug through nasal route. Spans were mixed with cholesterol at ratios of 1:1, 1:2, 1:3, and 1:4 of cholesterol to surfactant, respectively to prepare niosomes. Chitosan (CS) coated vesicles were prepared by mixing optimum niosomal formula with CS solution (0.6%). Physicochemical and stability parameters and confocal laser scanning microscopy (CLSM) of developed vesicles were determined. Also, the brain targeting properties of the optimized formula were measured in rats. Niosomes had entrapment efficiency more than 90% and particle size ranging from 201.3 ± 2.4 nm to 1446 ± 9 nm. TEM photomicrographs of developed vesicles showed a clear shell surrounding the coated vesicles. The produced vesicles exhibited 2.46 folds increase in the amount of drug that permeated nasal mucosa and prolonged OL release compared to drug solution. Coated niosomes further improved drug permeation. CLSM of coated optimum formula showed high permeation across the nasal mucosa. Stability studies revealed non-significant changes in the physicochemical parameters of optimum formula over the storage period. The optimized nasal CS-coated niosomes showed a three-fold increase in OL concentration in the brain compared to the intranasal solution of the drug. In conclusion, the developed vesicles were efficient in nasal delivery of OL into the brain.

Design, optimization, characterization, and in vivo evaluation of sterosomes as a carrier of metformin for treatment of lung cancer.

The present study aimed to formulate and evaluate metformin sterosomes. Sterosomes were prepared by incorporating stearylamine and cholesterol in different ratios. Sterosomes were characterized using size, zeta potential, entrapment efficiency (EE%) and in vitro release. Aerosol generated by nebulization was evaluated by a cooled Andersen cascade impactor (ACI) at 15 L/min. In vitro cytotoxicity of free and metformin-containing sterosomes was tested against human cancer cell lines. A comparative pharmacokinetic study between sterosomal formulation and free drug solution (750 mg) was performed. Spirometry was performed before and at time intervals after inhalation. The mean hydrodynamic diameter of the formulated vesicles was in the range of 288.7-578 nm. The EE% varied from 71 ± 1.4% to 89 ± 5.2%, with an optimum EE% of 89 ± 5.2at a lipid ratio of 2/1 stearylamine/cholesterol. Metformin sterosomes displayed an inhibitory effect on A549 lung cancer cell lines which significantly (p < 0.05) increased depending on dose and prolonged exposure time. Spirometric data were minimally changed before and after inhalation without a statistically significant difference in the forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or FEV1/FVC ratio (p > 0.05). Metformin-loaded sterosomes resulted in a significant increase in biological half-life (t1/2) with a mean value of 7.31 ± 1.04 h compared to 3.99 ± 0.17 h of the solution form. However, the peak plasma concentration of metformin sterosomes was lower than that achieved by metformin-free solution aerosol, and the difference was statistically significant (p < 0.05).The eligibility of sterosomes for aerosol delivery by nebulization would provide a novel strategy for delivery of metformin by inhalation as a potentially effective inhalation treatment of lung cancer.

Changing the morphology of one-dimensional titanate nanostructures affects its tissue distribution and toxicity.

The present research investigated the impact of the morphology change of titanate (TiO2) nanostructures on its tissue distribution and toxicity. The TiO2 nanotubes, rods, and ribbons were synthesized by the hydrothermal technique, and the morphology was adjusted by alteration of the hydrothermal duration time. The characterization techniques were X-ray diffraction, high-resolution transmission electron microscopy, dynamic light scattering, and the Brunauer-Emmett-Teller method for measuring the surface area. The intravenously administrated dose (5 mg/kg) was injected as a single dose for 1 day and consecutively for 42 days. The quantitative analysis of accumulated TiO2 nanostructures in the liver, spleen, and the heart was performed using an inductively coupled plasma emission spectrometer, and the organs' toxicity was estimated by histopathological analysis. The prepared nanostructures exhibited differences in morphology, crystallinity, size distribution, surface area, zeta potential, and aspect ratio. The results revealed a tissue distribution difference between the liver, spleen, and heart of these nanostructures, the distribution order was the liver, spleen, and the heart for all TiO2 nanostructures. The toxicity was induced with different degrees. The nanotubes were the most harmful among the three formats. In summary, changes in the morphology of the TiO2 nanostructures change its distribution and toxicity.

Proniosomal Microcarriers: Impact of Constituents on the Physicochemical Properties of Proniosomes as a New Approach to Enhance Inhalation Efficiency of Dry Powder Inhalers.

Proniosomes are free-flowing systems with coating carriers, which developed as a method for improving the drug flow and pulmonary delivery. Extensive research on proniosomes was done to enhance the dry powder inhalers (DPI)'s inhalation performance. This research aimed at studying the impact of lactose-mannitol mixture additives on the proniosome's physicochemical properties as a method for improving the inhalation efficiency of DPI. Vismodegib has been employed as a compound model. Box-Behnken design has been employed to prepare different proniosomes formulae by incorporating various (A) span 60 concentrations, (B) lactose concentrations and (C) mannitol: total carrier mixture. The measured responses were vesicle size (R1), %release (R2), Carr's index (R3) and %recovery (R4). The results displayed that R1 and R4 were significantly antagonistic to C and significantly synergistic to both A and B while R2 and R3 were significantly synergistic to C and significantly antagonistic to both A and B. The optimal formula was selected for its aerodynamic behaviour, cytotoxic activity and bioavailability assessment. The optimal formula resulted in better Vismodegib lung deposition, cytotoxic activity and relative bioavailability. This novel formula could be a promising carrier for sustained delivery of drugs via the pulmonary route.

Treatment of Basal Cell Carcinoma Via Binary Ethosomes of Vismodegib: In Vitro and In Vivo Studies.

Vismodegib (VMD) is a hedgehog inhibitor which indicated for basal cell skin cancer (BCC). This work focuses on investigating the influence of isopropyl alcohol additive for topical delivering and targeting of VMD-loaded binary ethosomes for BCC treatment. Different binary ethosome formulae were prepared based on Box-Behnken design using different concentrations of phospholipid (A), cholesterol (B) and isopropyl alcohol/total alcohol ratio (C). The prepared formulae were characterized for %entrapment efficiency (R1), vesicle size (R2), %release (R3) and steady-state flux (R4). Increasing A, B and C resulted in significant increase of R1 and R2 and significant decrease of R3 and R4. The optimization was achieved and the optimum formula was selected to investigate its anti-tumour efficacy in vivo. The optimum formula showed a localized VMD and consequently a significant anti-tumour activity compared with oral VMD. Briefly, VMD-loaded binary ethosome gel could be an effective treatment of BCC with lower side effects. Graphical abstract.

Formulation development of self-nanoemulsifying drug delivery system of celecoxib for the management of oral cavity inflammation.

The oral administration of celecoxib (CLX) is a real problem because of its low aqueous solubility that results in high variability in absorption and its severe adverse effect such as cardiotoxic effects and gastrointestinal toxicity. Self-nanoemulsifying drug delivery systems (SNEDDS) can enhance the poor dissolution and erratic absorption of poorly water-soluble drugs such as CLX. This study was conducted to investigate the potential of SNEDDS to enhance the efficacy of CLX on inflamed mucous tissue and reduce systemic adverse effects by increasing its poor dissolution properties. A pseudo-ternary phase diagram was derived from the results of CLX solubility experiments in various excipients. These studies revealed the use of Labrafil M 2515 CS as oil, tween 80 as a surfactant, and polyethylene glycol 400 as a co-surfactant for the optimization of SNEDDS formulations. Eight formulations were formulated and characterized by their particle size, polydispersity index, viscosity, globular shape, drug solubility, self-emulsification efficiency, in vitro drug release, and permeation. The anti-inflammatory effect of CLX-SNEDDS was evaluated by carrageenan-induced cheek oedema in rats. The cheeks were treated with CLX-SNEDDS before oedema induction and then noticed for narrow periods (2 h) followed by histopathological studies to determine the efficacy of treatment. The selected formulations (F3 and F5) showed spherical morphologies under transmission electron microscopy, mean droplet sizes of 116.9 ± 1.78 and 124 ± 1.87 nm, respectively, complete in vitro drug release, and high cumulative amounts of drug permeation in 8 h. They also showed significant remarkable cheek oedema inhibition in comparison with the control groups (p < 0.05). CLX-SNEDDS was found to achieve effective local therapeutic concentration and intended to reduce cheek oedema, congestive capillary, inflammatory cells, and side effects due to lower dose size.

Formulation design and optimization of novel soft glycerosomes for enhanced topical delivery of celecoxib and cupferron by Box-Behnken statistical design.

BACKGROUND: The present study describes glycerosomes (vesicles composed of phospholipids, glycerol and water) as a novel drug delivery system for topical application of celecoxib (CLX) and cupferron (CUP) compound. AIM: The goal of this research was to design topical soft innovative vesicles loaded with CLX or CUP for enhancing the efficacy and avoiding systemic toxicity of CLX and CUP. METHODS: CLX and CUP loaded glycerosomes were prepared by hydrating phospholipid-cholesterol films with glycerol aqueous solutions (20-40%, v/v). Box-Behnken design, using Design-Expert® software, was the optimum choice to statistically optimize formulation variables. Three independent variables were evaluated: phospholipid concentration (X1), glycerol percent (X2) and tween 80 concentration (X3). The glycerosomes particle size (Y1), encapsulation efficiency percent (Y2: EE %) and drug release (Y3) were selected as dependent variables. The anti-inflammatory effect of CLX and CUP glycerosomal gel was evaluated by carrageenan-induced rat paw edema method followed by histopathological studies. RESULTS: The optimized formulations (CLX2* and CUP1*) showed spherical morphology under transmission electron microscopy, optimum particle size of 195.4 ± 3.67 nm, 301.2 ± 1.75 nm, high EE of 89.66 ± 1.73%, 93.56 ± 2.87%, high drug release of 47.08 ± 3.37%, 37.60 ± 1.89% and high cumulative amount of drug permeated in 8 h of 900.18 ± 50.24, 527.99 ± 34.90 µg.cm-2 through hairless rat skin, respectively. They also achieved significant remarkable paw edema inhibition in comparison with the control group (p < .05). CONCLUSION: Finally, the administration of CLX2* and CUP1* loaded glycerosomal gel onto the skin resulted in marked reduction of edema, congestive capillary and inflammatory cells and this approach may be of value in the treatment of different inflammatory disorders.

A novel synergistic enzyme-antibiotic therapy with immobilization of mycobacteriophage Lysin B enzyme onto Rif@UiO-66 nanocomposite for enhanced inhaled anti-TB therapy; Nanoenzybiotics approach.

The emergence of antibiotic-resistant and phage-resistant strains of Mycobacterium tuberculosis (M. tuberculosis) necessitates improving new therapeutic plans. The objective of the current work was to ensure the effectiveness of rifampicin and the mycobacteriophage LysB D29 (LysB)enzyme in the treatment of multi-drug resistant tuberculosis (MDR-TB) infection, where new and safe metal-organic framework (MOF) nanoparticles were used in combination. UiO-66 nanoparticles were synthesized under mild conditions in which the antimycobacterial agent (rifampicin) was loaded (Rif@UiO-66) and LysB D29 enzyme immobilized onto Rif@UiO-66, which were further characterized. Subsequently, the antibacterial activity of different ratios of Rif@UiO-66 and LysB/Rif@uio-66 against the nonpathogenic tuberculosis model Mycobacterium smegmatis (M. smegmatis) was evaluated by minimum inhibitory concentration (MIC) tests. Impressively, the MIC of LysB/Rif@uio-66 was 16-fold lower than that of pure rifampicin. In vitro and in vivo toxicity studies proved that LysB/Rif@UiO-66 is a highly biocompatible therapy for pulmonary infection. A biodistribution assay showed that LysB/Rif@UiO-66 showed a 5.31-fold higher drug concentration in the lungs than free rifampicin. A synergistic interaction between UiO-66, rifampicin and the mycobacteriophage lysB D29 enzyme was shown in the computational method (docking). Therefore, all results indicated that the LysB/Rif@UiO-66 nanocomposite exhibited promising innovative enzyme-antibiotic therapy for tuberculosis treatment.

Fabrication and application of targeted ciprofloxacin nanocarriers for the treatment of chronic bacterial prostatitis.

Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic secretion. Owing to poor blood supply to the prostate gland and limited drug penetration, CBP treatment is difficult. Transferosomes are ultradeformable vesicles for nanocarrier applications, which have become an important area of nanomedicine. Such carriers are specifically targeted to the pathological area to provide maximum therapeutic efficacy. It consists of a lipid bilayer soybean lecithin phosphatidylcholine (PC), an edge activator Tween 80 with various ratios, and a chloroform/methanol core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or among the lipid bilayer. Due to their exceptional flexibility, which enables them to squeeze themselves through narrow pores that are significantly smaller than their size, they can be a solution. One formulation (Cipro5 PEG) was selected for further in vitro analysis and was composed of phosphatidylcholine (PC), Tween 80, and polyethylene glycol-6 stearate (PEG-6 stearate) in a ratio of 3:3:1 in a chloroform/methanol mixture (1:2 v/v). In vitro, the results showed that PEGylated transferosomes had faster drug release, higher permeation, and increased bioavailability. The transferosomes were quantified with a particle size of 202.59 nm, a zeta potential of-49.38 mV, and a drug entrapment efficiency of 80.05%. The aim of this study was to investigate drug targeting. Therefore, Monoclonal antibody IgG was coupled with Cipro5 PEG, which has specificity and selectivity for conjugated nanoparticles. In vivo, a total of twenty-five adult Wistar rats were obtained and randomly divided into 5 groups, each of 5 rats at random: the control group, blank group, positive control group, Cipro 5PEG group, and Cipro 5PEG coupled with IgG antibody group. The cytokines levels (IL-1ß, IL-8, and TNF-α) in the serum were detected by analysis kits. Compared with the control group, treatment with Cipro 5PEG coupled with the IgG antibody could significantly inhibit cytokines, according to histological analysis. Cipro 5PEG, coupled with the IgG antibody group, reduced prostate tissue inflammation. Hence, our results show a promising approach to delivering antibiotics for the targeted therapy of CBP.

Preparation and characterization of mosapride citrate inclusion complexes with natural and synthetic cyclodextrins.

The aim of this work was to investigate the inclusion complexes between mosapride citrate and SBE7ß-CD in comparison with the natural ß-CD to enhance its bioavailability by improving the solubility and dissolution rate. The complexation efficiency value of SBE7ß-CD was higher than that for ß-CD. Solid binary systems of mosapride citrate with CDs were prepared by physical mixing, kneading and freeze-drying techniques at molar ratio of 1:1(drug:CD). Physicochemical characterization of the prepared systems was studied using X-ray diffractometry, differential scanning calorimetry, Fourier-transform infrared spectroscopy and scanning electron microscopy (SEM). Amorphous drug was detectable to large extent in inclusion complexes prepared using the freeze-drying technique. From the dissolution study of different inclusion complexes in simulated saliva solution (pH 6.8), we could concluded that irrespective of the preparation technique, the systems prepared using SBE7ß-CD showed better performance than the corresponding ones prepared using ß-CD. In addition, the freeze-drying technique showed superior dissolution enhancement than other methods especially when combined with the SBE7ß-CD.

Numerical Optimization of Prednisolone-Tacrolimus Loaded Ultraflexible Transethosomes for Transdermal Delivery Enhancement; Box-Behnken Design, Evaluation, Optimization, and Pharmacokinetic Study.

The aim of the present study is to formulate highly permeable carriers (i.e., transethosomes) for enhancing the delivery of prednisolone combined with tacrolimus for both topical and systemic pathological conditions. A Box-Behnken experimental design was implemented in this research. Three independent variables: surfactant concentration (X1), ethanol concentration (X2), and tacrolimus concentration (X3) were adopted in the design while three responses: entrapment efficiency (Y1), vesicle size (Y2), and zeta potential (Y3) were investigated. By applying design analysis, one optimum formulation was chosen to be incorporated into topical gel formulation. The optimized transethosomal gel formula was characterized in terms of pH, drug content, and spreadability. The gel formula was challenged in terms of its anti-inflammatory effect and pharmacokinetics against oral prednisolone suspension and topical prednisolone-tacrolimus gel. The optimized transethosomal gel achieved the highest rate of rat hind paw edema reduction (98.34%) and highest pharmacokinetics parameters (Cmax 133.266 ± 6.469 µg/mL; AUC0-∞ 538.922 ± 49.052 µg·h/mL), which indicated better performance of the formulated gel.

Design of transfersomal nanocarriers of nystatin for combating vulvovaginal candidiasis; A different prospective.

The objective of this study was to prepare and evaluate Nystatin (NYS) loaded transfersomes to achieve better treatment of vulvovaginal candidiasis. Nystatin transferosomes were formulated utilizing thin film hydration method. A 32 full factorial design was employed to evaluate the effect of different formulation variables. Two independent variables were chosen; the ratio between lecithin surfactant (X1) was set at three levels (10-40), and the type of surfactants (X2) was set at three levels (Span 60, Span 85 and Pluronic F-127). The dependent responses were; entrapment efficiency (Y1: EE %), vesicles size (Y2: VS) and release rate (Y3: RR). Design Expert® software was utilized to statistically optimize formulation variables. The vesicles revealed high NYS encapsulation efficiency ranging from 97.35 ± 0.03 to 98.01 ± 0.20% whereas vesicle size ranged from 194.8 ± 20.42 to 400.8 ± 42.09 nm. High negative zeta potential values indicated good stability of the prepared formulations. NYS release from transfersomes was biphasic and the release pattern followed Higuchi's model. The optimized formulation (F7) exhibited spherical morphology under transmission electron microscopy (TEM). In-vitro and in-vivo antifungal efficiency studies revealed that the optimized formula F7 exhibited significant eradication of candida infestation in comparison to free NYS. The results revealed that the developed NYS transfersomes could be a promising drug delivery system to enhance antifungal efficacy of NYS.

Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice.

To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box-Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box-Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers.

Brain Targeting of Quetiapine Fumarate via Intranasal Delivery of Loaded Lipospheres: Fabrication, In-Vitro Evaluation, Optimization, and In-Vivo Assessment.

A liposphere system for intranasal delivery of quetiapine fumarate (QTF) was created to assess the potential for enhanced drug delivery. We investigated the effects of particle size, entrapment effectiveness, poly dispersibility index, and pluronic incorporation percentage on these variables. The optimal formula was examined using a TEM, and investigations into DSC, XRD, and FTIR were made. Optimized liposphere formulation in vitro dissolution investigation with a mean diameter of 294.4 ± 18.2 nm revealed about 80% drug release in 6 h. The intranasal injection of QTF-loaded lipospheres showed a shorter Tmax compared to that of intranasal and oral suspension, per the findings of an in vivo tissue distribution investigation in Wistar mice. Lipospheres were able to achieve higher drug transport efficiency (DTE %) and direct nose-to-brain drug transfer (DTP %). A potentially effective method for delivering QTF to specific brain regions is the liposphere system.

Brain uptake and accumulation of new levofloxacin-doxycycline combination through the use of solid lipid nanoparticles: Formulation; Optimization and in-vivo evaluation.

The objective of this study is to investigate the feasibility of delivery of novel levofloxacin/ doxycycline (LEVO/DOX) combination to the brain by intranasal route to achieve a significant local concentration in the brain and a direct nose-to-brain pathway. Solid lipid nanoparticles (SLN) were selected as a drug carrier and employed Box-Behnken design for optimizing LEVO/DOX-SLN to achieve minimum particle size and maximum apparent entrapment efficiency (EE). SLNs were prepared by hot emulsification and characterized. In vitro release of optimized formulations showed prolonged drug release from the optimized formulation. The results of pharmacokinetic study of the optimized SLN-HPMC gel in plasma and brain revealed significant increase in the brain peak concentration (420, 315 ng/g), the AUC 0-360 min (57130 and 48693.13 ng. min/g) in comparison to intranasal LEVO/DOX free solution with the values of (160, 120) ng/g, (36850, 27637.5 ng⋅min/g) for LEVO and DOX, respectively. The optimized LD-SLN-HPMC gel gave a drug-targeting efficiency (DTE %) of 149.815 and 161.969 for LEVO and DOX, respectively, in comparison to the intravenous route. Moreover, the optimized formulation had a direct transport percentage (DTP %) of 33.285 and 40.236 for LEVO and DOX, respectively, which indicates a significant contribution of direct nose-to-brain pathway in brain drug delivery.

The Impact of Adding a Training Device to Familiar Counselling on Inhalation Technique and Pulmonary Function of Asthmatics.

INTRODUCTION: We have investigated the effect of adding a pressurized metered dose inhaler (pMDI) training device to verbal counselling on pulmonary function and inhalation technique. METHODS: A total of 304 adult asthmatic subjects (> 18 years old) were enrolled in a 3-month study of assessment and education. They were divided into an investigation group (Trainhaler plus Flo-Tone and verbal counselling, n = 261, mean age 49.2 years) and a control group (verbal counselling only, n = 43, mean age 48.7 years). Pulmonary function and inhalation technique were evaluated, mistakes noted, and the correct technique advised at three consecutive monthly visits. Visits also included verbal pMDI counselling (both groups) and training device coaching (investigation group). RESULTS: By visit 2, the mean number of technique errors decreased significantly (p < 0.05) in both groups (investigation group p < 0.001). The investigation group demonstrated a marked decrease in the frequency of the critical error of maintaining a slow inhalation rate until the lungs are full-a technique difficult to learn via verbal counselling alone. The improvement in pulmonary function was significant from the second clinic visit in the investigation group (p < 0.05) and from the third visit in both groups (p < 0.001). CONCLUSIONS: Use of a training device combined with verbal counselling improved inhalation technique. An earlier, significant improvement was also noted in pulmonary function.