Percentage Entrapment Efficiency Research Articles

Preparation of Artemisia Turcomanic Encapsulated Niosomal Nanocarriers and Evaluation of Anticancer Activities and Apoptosis Gene Expression Analysis in HeLa Cells.

Artemisia turcomanic as a natural antibacterial agent, exhibited significant antibacterial effect in the treatment against cancer. This study is the first to investigate size, encapsulation efficiencies, release behavior of Artemisia turcomanic loaded niosomal nanocarriers , and the anticancer effect of niosomal nanocarriers by MTT assay, flow cytometry, and real time (on Hela cell lines). When the molar ratio of cholesterol: surfactant was 1:2 and the liquid content was 300 µmol, the highest percentage of entrapment efficiency was 83.25%. Moreover, niosomal formulation showed a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 5.4). In addition, The apoptotic rate of Artemisia loaded niosomes on Hela cell lines was higher than free extract and pristine niosome. Also, reduction in the expression levels of Bcl2, caspase-3, and p53 genes and increase in the expression level of BAX after treatment with Artemisia turcomanic-loaded niosomes were more significant than those after treatment with free Artemisia turcomanic and blank niosome. The cytotoxicity results of samples presented that Artemisia turcomanic loaded niosomes are more beneficial in the death of Hela cell lines.

PEGylated Erlotinib HCl Injectable Nanoformulation for Improved Bioavailability.

The present study was undertaken to synthesize PEGylated monomethoxy poly (ethylene glycol)-poly (ε-Caprolactone) (mPEG-PCL) block copolymer and formulate Erlotinib HCl-loaded mPEG-PCL nanoparticles for enhancing the bioavailability of the drug. Using the ring-opening polymerization technique, PEGylated mPEG-PCL block copolymer was synthesized, and the structure of the copolymer was characterized using FTIR, 1H-NMR, and DSC techniques. The solvent evaporation approach was used to effectively encapsulate Erlotinib HCl within block copolymeric nanoparticles. Erlotinib HCl-loaded mPEG-PCL nanoparticles had a mean particle size of 146.5 ± 2.37 nm and a zeta potential of -27.8 ± 2.77mV. The nanoparticles had a percent entrapment efficiency of 80.78 ± 0.09%. The in vitro drug release of Erlotinib HCl-loaded copolymeric nanoparticles showed a slow and sustained release behavior which could be maintained for up to 72 h. The Korsmeyer-Peppas fitting findings indicated that the drug release process followed a non-Fickian diffusion mechanism. The pharmacokinetic (PK) behavior of the developed nanoformulation was studied in albino Wistar rats, and the relative bioavailability of the optimized NP formulation given by intravenous route was found to be 187.33%. The PK data suggested that Erlotinib HCl-loaded mPEG-PCL copolymeric nanoparticles can dramatically alter the PK behavior of Erlotinib HCl and greatly improve the drug's bioavailability by as much as three times when compared to the oral formulation. As a result, it was established that the block copolymeric nanoparticles have promise for the effective encapsulation of Erlotinib HCL for an injectable formulation with increased bioavailability.

Fabrication and Assessment of Orodispersible Tablets Loaded with Cubosomes for the Improved Anticancer Activity of Simvastatin against the MDA-MB-231 Breast Cancer Cell Line.

Various factors limit the use of simvastatin as an anticancer drug. Therefore, this study aimed to analyse simvastatin (SIM)-loaded cubosome efficacy against breast cancer. SIM-loaded cubosomes were prepared using the emulsification method using different glyceryl monooleate, Pluronic F127 (PF-127), and polyvinyl alcohol (PVA) ratios. The best cubosomal formula was subjected to an in vitro cytotoxicity analysis using the human breast cancer cell line, MDA-MB-231 (MDA) (ATCC, HTB-26), and formulated as oral disintegrating tablets through direct compression. PF-127 and PVA positively affected drug loading, and the entrapment efficiency percentage of different SIM-cubosomal formulations ranged from 33.52% to 80.80%. Vesicle size ranged from 181.9 ± 0.50 to 316.6 ± 1.25 nm. PF-127 enhanced in vitro SIM release from cubosome formulations due to its solubilising action on SIM. The in vitro dissolution analysis indicated that SIM exhibited an initial dissolution of 10.4 ± 0.25% within the first 5 min, and 63.5 ± 0.29% of the loaded drug was released after 1 h. Moreover, cubosome formula F3 at 25 and 50 µg/mL doses significantly decreased MDA cell viability compared to the 12.5 µg/mL dose. The untreated SIM suspension and drug-free cubosomes at all doses had no significant influence on MDA cell viability compared to the control.

Development of Diphenyl carbonate-Crosslinked Cyclodextrin Based Nanosponges for Oral Delivery of Baricitinib: Formulation, Characterization and Pharmacokinetic Studies.

The aim of the present investigation is to prepare baricitinib (BAR)-loaded diphenyl carbonate (DPC) β-cyclodextrin (βCD) based nanosponges (NSs) to improve the oral bioavailability. BAR-loaded DPC-crosslinked βCD NSs (B-DCNs) were prepared prepared by varying the molar ratio of βCD: DPC (1:1.5 to 1:6). The developed B-DCNs loaded with BAR were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), % yield and percent entrapment efficiency (%EE). Based on the above evaluations, BAR-loaded DPC βCD NSs (B-CDN3) was optimized with mean size (345.8±4.7 nm), PDI (0.335±0.005), Yield (91.46±7.4%) and EE (79.1±1.6%). The optimized NSs (B-CDN3) was further confirmed by SEM, spectral analysis, BET analysis, in vitro release and pharmacokinetic studies. The optimized NSs (B-CDN3) showed 2.13 times enhancement in bioavailability in comparison to pure BAR suspension. It could be anticipated that NSs loaded with BAR as a promising tool for release and bioavailability for the treatment of rheumatic arthritis and Covid-19.

Preparation and Evaluation of Niosomal Transdermal Patch of Clozapine

Niosomes are the non-ionic surfactant vesicles obtained on hydration of synthetic non-ionic surfactants. These are the promising vehicles for effective transdermal drug delivery. The present research work was aimed to develop niosomal-based transdermal Clozapine patch containing a stable formulation with improved drug permeation. Niosomes were prepared by solvent casting method. All the formulations were evaluated for vesicle size, zeta potential and percent entrapment efficiency. All the patches were then characterized for thickness, folding endurance, drug content determination, Flatness, and in vitro permeation studies. F3 formulation having optimum vesicle size (2.6m), highest zeta potential (-32.56mV) and maximum percent entrapment efficiency (98.09%) was selected as optimized formulation. The transdermal patch was prepared using solvent casting method from the optimised niosomes formulation F3 formulation. The prepared optimised niosomes F3 formulation were loaded into the patch formulation. Patches loaded with niosomes (F3NT3) showed 95.78 % cumulative amount of drug permeated. The optimized formulation (F3NT3) followed first order release kinetics.

Development and Evaluation of Novel Encapsulated Isoeugenol-Liposomal Gel Carrier System for Methicillin-Resistant Staphylococcus aureus.

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) bacteria have seriously threatened the health and safety of the world's population. This challenge demands the development of alternative therapies based on plant origin. This molecular docking study ascertained the orientation and intermolecular interactions of isoeugenol within penicillin-binding protein 2a. In this present work, isoeugenol as an anti-MRSA therapy was selected by encapsulating it into a liposomal carrier system. After encapsulation into the liposomal carrier, it was evaluated for encapsulation efficiency (%), particle size, zeta potential, and morphology. The percentage entrapment efficiency (% EE) was observed to be 57.8 ± 2.89% with a particle size of 143.31 ± 7.165 nm, a zeta potential of (-)25 mV, and morphology was found to be spherical and smooth. After this evaluation, it was incorporated into a 0.5% Carbopol gel for a smooth and uniform distribution on the skin. Notably, the isoeugenol-liposomal gel was smooth on the surface with a pH of 6.4, suitable viscosity, and spreadability. Interestingly, the developed isoeugenol-liposomal gel was safe for human use, with more than 80% cell viability. The in vitro drug release study shows promising results with 75.95 ± 3.79% of drug release after 24 h. The minimum inhibitory concentration (MIC) was 8.236 µg/mL. Based on this, it can be concluded that encapsulating isoeugenol into the liposomal gel is a potential carrier for MRSA treatment.

Formulation and Evaluation of Niosomal Gel Loaded with Asparagus racemosus Extract for Anti-inflammatory Activity

Abstract: Background/Aim: Inflammation typically occurs when infectious microorganisms enter the body, settle in specific tissues, and/or circulate in the blood. Asparagus racemosus extract contains various saponins and flavonoids and plant-origin drugs have fewer side effects and toxicity. The phytoconstituents have less permeability through the skin; to enhance their permeability and effectiveness it was loaded in niosomes. Therefore, the study aimed to formulate and characterize the niosomal gel loaded with Asparagus racemosus extract for anti-inflammatory activity. Materials and Methods: The niosomes containing saponins in the extract were prepared using thin film hydration method and 23 full factorial design was employed to assess the influence of independent variables span 60 and cholesterol on vesicle size, PDI, zeta potential, and percentage entrapment efficiency. 10% of niosomal and conventional gels were prepared by incorporating optimized niosomes and extract containing total saponin in 1% carbopol gel. Ex vivo permeability studies of prepared gels were performed through goat skin using Franz diffusion cell. An anti-inflammatory study was conducted on albino rat. Results: The statistical analysis revealed the significant effect of independent variables on vesicle size, PDI, entrapment efficiency and zeta potential. SEM image shows vesicles are spherical in shape and uniform in size. The niosomal gel provided a significantly higher amount of steady-state flux and permeability coefficient into the skin than conventional gel. The animal model proved that niosomal gel loaded with total saponins in extract showed significant anti-inflammatory compared to the control. Conclusion: It was concluded that the niosomal gel had better efficacy than the conventional gel. Keywords: Asparagus racemosus, Niosomes, Span 60, Cholesterol, Factorial design, Carbopol 934.

Formulation and Characterisation of Cilnidipine Microsponge Loaded Hydrogels for Antihypertensive Activity

Background: Owing to presystemic metabolism following oral drug delivery, most antihypertensive medications have a low bioavailability. Cilnidipine is a calcium channel blocker used to treat mild to moderate hypertension. Cilnidipine's bioavailability is reduced by 13% due to substantial presystemic metabolism. Objective: The study aimed to fabricate non-irritant and stable microsponge-based hydrogel to enhance the bioavailability of cilnidipine, a weakly water-soluble medication. In addition, the goal was to enhance the permeation rate and retention time at the site of application. Methods: Formulation was developed by using a two-level factorial design with Design Expert software version 13 (14-day free trial). Microsponges were formulated by the emulsion solvent diffusion method, followed by evaluating responses, such as particle size, percentage entrapment efficiency, in vitro drug release, and surface morphology. In addition, X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FT-IR) were performed. Viscosity, swelling behaviour, spreadability, in vitro diffusion, skin irritancy using Wistar albino rats, and in vitro permeation using goat skin were assessed, and stability studies were performed after incorporating the finest formulation into the gel base. Results: Fabricated microsponges were found to be within the required micro dimensions having the necessary porous morphology as demonstrated by scanning electron microscopy studies. Drug entrapment efficiency was found to be in the range of 75-88%. The extended medicament release duration of up to 8 hours was observed. The diffusion data showed controlled release, as demonstrated by Higuchi’s plot. In vitro permeation studies displayed enhanced medicament retention and permeation rate at the site of application. Conclusion: The fabricated microsponge drug delivery system was found to be stable, non-irritant, and having enhanced permeation rate and retention time.

Self-Assembling Lecithin-Based Mixed Polymeric Micelles for Nose to Brain Delivery of Clozapine: In-vivo Assessment of Drug Efficacy via Radiobiological Evaluation.

The research objective is to design intranasal brain targeted CLZ loaded lecithin based polymeric micelles (CLZ- LbPM) aiming to improve central systemic CLZ bioavailability. In our study, intranasal CLZ loaded lecithin based polymeric micelles (CLZ- LbPM) were formulated using soya phosphatidyl choline (SPC) and sodium deoxycholate (SDC) with different CLZ:SPC:SDC ratios via thin film hydration technique aiming to enhance drug solubility, bioavailability and nose to brain targeting efficiency. Optimization of the prepared CLZ-LbPM using Design-Expert® software was achieved showing that M6 which composed of (CLZ:SPC: SDC) in respective ratios of 1:3:10 was selected as the optimized formula. The optimized formula was subjected to further evaluation tests as, Differential Scanning Calorimetry (DSC), TEM, in vitro release profile, ex vivo intranasal permeation and in vivo biodistribution. The optimized formula with the highest desirability exhibiting (0.845), small particle size (12.23±4.76 nm), Zeta potential of (-38 mV), percent entrapment efficiency of > 90% and percent drug loading of 6.47%. Ex vivo permeation test showed flux value of 27 μg/cm².h and the enhancement ratio was about 3 when compared to the drug suspension, without any histological alteration. The radioiodinated clozapine ([131I] iodo-CLZ) and radioiodinated optimized formula ([131I] iodo-CLZ-LbPM) were formulated in an excellent radioiodination yield more than 95%. In vivo biodistribution studies of [131I] iodo-CLZ-LbPM showed higher brain uptake (7.8%± 0.1%ID/g) for intranasal administration with rapid onset of action (at 0.25 h) than the intravenous formula. Its pharmacokinetic behavior showed relative bioavailability, direct transport percentage from nose to brain and drug targeting efficiency of 170.59%, 83.42% and 117% respectively. The intranasal self-assembling lecithin based mixed polymeric micelles could be an encouraging way for CLZ brain targeting.

Optimization and In Vitro Characterization of Telmisartan Loaded Sodium Alginate Beads and Its In Vivo Efficacy Investigation in Hypertensive Induced Animal Model.

Antihypertensive drug telmisartan (TEL) belongs to BCS class II, which is characterized by low water solubility and, consequently, low oral bioavailability. Gastroretentive systems may overcome the problems associated with low solubility of TEL and incomplete absorption by localizing the drug release in the stomach. The purpose of this study was to prepare TEL-loaded, oil-entrapped, floating alginate beads with the intent of enhancing the oral bioavailability of TEL for the treatment of hypertension. For the formulation and optimization of seventeen formulations of TEL-loaded oil-entrapped floating alginate beads, a central composite design was utilized. The concentration of sodium alginate (X1), the concentration of cross-linker (X2), and the concentration of sesame oil (X3) served as independent variables, whereas the entrapment efficiency (Y1), in vitro buoyancy (Y2), and drug release Q6h (Y3) served as dependent variables. Using the emulsion gelation method and calcium chloride as the cross-linking agent, different formulations of TEL alginate beads were produced. All formulations were evaluated for their entrapment efficiency percentage, in vitro buoyancy, and in vitro drug release. The optimal formulation of TEL alginate beads was prepared with and without oil and evaluated for entrapment efficiency percentage, in vitro buoyancy, swelling ratio, average size, and in vitro drug release. Using scanning electron microscopes, the surface morphology was determined. Using IR spectroscopy, the compatibility between the ingredients was determined. In vivo evaluation of the optimized formulation in comparison to the free TEL was done in hypertension-induced rats, and the systolic blood pressure and all pharmacokinetic parameters were measured. The prepared beads exhibited a high entrapment efficiency percentage, in vitro buoyancy, and prolonged drug release. TEL was compatible with other ingredients, as approved by IR spectroscopy. The prepared TEL beads were spherical, as shown by the SEM. The relative bioavailability of TEL-loaded oil-entrapped beads was 222.52%, which was higher than that of the pure TEL suspension. The prepared TEL beads formulation exhibited a higher antihypertensive effect for a prolonged time compared to pure TEL suspension. It can be concluded that this innovative delivery method of TEL-loaded oil-entrapped beads is a promising tool for enhancing drug solubility and, thus, oral bioavailability and therapeutic efficacy, resulting in enhanced patient compliance. Furthermore, the in vivo study confirmed the formulation's extended anti-hypertensive activity in animal models.

A comprehensive review on recent nanosystems for enhancing antifungal activity of fenticonazole nitrate from different routes of administration

This review aims to comprehensively highlight the recent nanosystems enclosing Fenticonazole nitrate (FTN) and to compare between them regarding preparation techniques, studied factors and responses. Moreover, the optimum formulae were compared in terms of in vitro, ex vivo and in vivo studies in order to detect the best formula. FTN is a potent antifungal imidazole compound that had been used for treatment of many dangerous fungal infections affecting eye, skin or vagina. FTN had been incorporated in various innovative nanosystems in the recent years in order to achieve significant recovery such as olaminosomes, novasomes, cerosomes, terpesomes and trans-novasomes. These nanosystems were formulated by various techniques (ethanol injection or thin film hydration) utilizing different statistical designs (Box-Behnken, central composite, full factorial and D-optimal). Different factors were studied in each nanosystem regarding its composition as surfactant concentrations, surfactant type, amount of oleic acid, cholesterol, oleylamine, ceramide, sodium deoxycholate, terpene concentration and ethanol concentration. Numerous responses were studied such as percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), and in vitro drug release. Selection of the optimum formula was based on numerical optimization accomplished by Design-Expert® software taking in consideration the largest EE %, ZP (as absolute value) and in vitro drug release and lowest PS and PDI. In vitro comparisons were done employing different techniques such as Transmission electron microscopy, pH determination, effect of gamma sterilization, elasticity evaluation and docking study. In addition to, ex vivo permeation, in vivo irritancy test, histopathological, antifungal activity and Kinetic study.

Chitosan Surface-Modified PLGA Nanoparticles Loaded with Cranberry Powder Extract as a Potential Oral Delivery Platform for Targeting Colon Cancer Cells

Nutraceutical cranberry powder extract (CBPE) has distinct polyphenols inhibiting colon cancer growth and proliferation. However, its oral therapeutic efficacy is hindered because of its low permeability. This study aims to formulate chitosan surface-modified PLGA nanoparticles (CS-PLGA NPs) for encapsulating CBPE and modulating its release rate, permeation, cell targeting, and, therefore, its cytotoxicity. A full 23 factorial design is employed to scrutinize the effect of lactide/glycolide ratio, PLGA weight, and stabilizer concentrations on entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formula (F4) shows spherical particles with a relatively high EE% (72.30 ± 2.86%), an appropriate size of 370.10 ± 10.31 nm, PDI; 0.398 ± 0.001, and ZP; -5.40 ± 0.21 mV. Alongside the ATR-FTIR outcomes, the chitosan surface-modified formula (CS-F4) demonstrates a significant increase in particle size (417.67 ± 6.77 nm) and a shift from negative to positive zeta potential (+21.63 ± 2.46 mV), confirming the efficiency of surface modification with chitosan. The intestinal permeability of F4 and CS-F4 is significantly increased by 2.19- and 3.10-fold, respectively, compared to the CBPE solution, with the permeability coefficient (Papp) being 2.05 × 10-4 cm/min and 2.91 × 10-4 cm/min, for F4 and CS-F4, respectively, compared to the CBPE solution, 9.36 × 10-5 cm/min. Moreover, CS-F4 evidences significant caspase-3 protein level expression stimulation and significant inhibition of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription-3 (STAT-3) protein expression levels, confirming the superiority of CS-F4 for targeting HT-29 cells. Briefly, CS-PLGA NPs could be regarded as a prosperous delivery system of CBPE with enhanced permeation, cell targeting, and antitumor efficacy.

Diosmin-Loaded Nanoemulsion-Based Gel Formulation: Development, Optimization, Wound Healing and Anti-Inflammatory Studies.

The wound-healing process is complex and prone to interruption or failure, which can result in the development of chronic wounds that never heal. This can be overcome by seeking prompt medical attention, which will reduce the likelihood of complications and speed up the healing of the cutaneous wound. It has been established that functionalized engineered biomaterials are a possible strategy for starting skin wound care. The purpose of the current study is to develop a diosmin (DSM)-loaded nanoemulsion (NE)-based gel formulation and to investigate its wound healing and anti-inflammatory activity on rats. The DSM-loaded NEs (F1-F17) were developed and optimized with the help of Box-Behnken Design Expert. The DSM-Nes were developed using lauroglycol 90 (LG90®) as oil, Tween-80 as surfactant and transcutol-HP (THP) as co-surfactant. The optimized Nes showed globule size (41 ± 0.07 nm), polydispersity index (PDI) (0.073 ± 0.008) and percentage of entrapment efficiency (%EE) (87 ± 0.81%). This optimized DSM-loaded NEs (F1) was further evaluated and incorporated into 1% carbopol 940 gel. F1-loaded gel was then characterized for drug content, spreadability, in vitro release, wound healing, and anti-inflammatory studies. The developed gel of DSM was found to show significantly better (p < 0.05) wound-healing and anti-inflammatory activity.

Integration of terpesomes loaded Levocetrizine dihydrochloride gel as a repurposed cure for Methicillin-Resistant Staphylococcus aureus (MRSA)-Induced skin infection; D-optimal optimization, ex-vivo, in-silico, and in-vivo studies

The intention of this work is to assess the repurposed antimicrobial impact of Levocetirizine dihydrochloride (LVC), which is a well-known antihistaminic drug, in addition, to augment the antimicrobial effect by using terpene-enriched vesicles (TPs). To investigate how various parameters affect TPs aspects, TPs were made employing the ethanol-injection-method and optimized d-optimal design. The TPs were characterized based on their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum TP was submitted to more examinations. The optimum TP (TP12) showed a spherical vesicle having an EE% of 66.39 ± 0.12%, PS of 243.3 ± 4.60 nm, PDI of 0.458 ± 0.003, and ZP of 24.2 ± 0.55 mV. The in-vitro release study results demonstrated that LVC is sustainedly liberated from the optimum TP compared to LVC-solution. The ex-vivo assessment showed that LVC was released in a more sustained manner from TPs-gel related to LVC solution, optimum TP, and LVC gel. Ex-vivo visualization by confocal laser scanning microscopy showed good deposition of the fluorescein-labeled TP. Further, the in-vitro anti-bacterial effect and biofilm inhibition and detachment assessment confirmed the potency of LVC against Methicillin-resistant-Staphylococcus-aureus (MRSA). The in-silico study demonstrated that the LVC has excellent stability with other ingredients combined with it in the TPs, further, it proved that LVC is a potential candidate for treating MRSA. In-vivo assessments revealed a good antimicrobial effect toward MRSA infection. Moreover, the histopathological evaluation confirmed the safety of using TPs-gel topically. In conclusion, MRSA-related skin infections may be treated using the LVC loaded TPs-gel as a promising system.

Design, Development and Characterization of Hyaluronic Acid Based pH Sensitive Liposomal In Situ Gel for the Treatment of Keratoconjunctivitis Sicca

The recent advances in ocular drug delivery have been successful in surpassing conventional therapy, owing to its considerable limitations. This study aims to develop and optimize in-situ liposomal ocular system to design once-daily liquid preparation to treat Keratoconjunctivitis sicca. Liposomes of Hyaluronic acid were prepared using soya lecithin by a thin film hydration method. Eight trial formulations were made by keeping drug as fixed ratio and varying the concentration of cholesterol and soya lecithin. The optimized formulation was selected for the formulation of liposomal in-situ hydrogel. Optimization was carried out by Central Composite Design (CCD) studying the factors, amount of cholesterol and soya lecithin and its effects on the responses, % In- vitro drug release (R1) and Percent Entrapment Efficiency (% EE) (R2). The best predicted model for R1 was the Quadratic model and, for R2 was Two-Factor Interaction model (2FI) without any significant lack of fit. Optimum formulation was found to be at 1:1:4 (drug: cholesterol: soya lecithin) showed sustained drug release of 31.28% in 8 hours with highest %EE of 47.36%. Liposomal in-situ gel preparation retained better stability throughout the study period when stored at refrigerator temperature and displayed prolonged action (76.44%) when compared to liposomal formulation (68.72%).&#x0D; Keywords: Liposomes, Hyaluronic acid, Optimized formulation, CCD, sustained drug release, in-situ hydrogel.

Exploring the Synergistic Effect of Bergamot Essential Oil with Spironolactone Loaded Nano-Phytosomes for Treatment of Acne Vulgaris: In Vitro Optimization, In Silico Studies, and Clinical Evaluation.

The foremost target of the current work was to formulate and optimize a novel bergamot essential oil (BEO) loaded nano-phytosomes (NPs) and then combine it with spironolactone (SP) in order to clinically compare the efficiency of both formulations against acne vulgaris. The BEO-loaded NPs formulations were fabricated by the thin-film hydration and optimized by 32 factorial design. NPs' assessments were conducted by measuring entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In addition, the selected BEO-NPs formulation was further combined with SP and then examined for morphology employing transmission electron microscopy and three months storage stability. Both BEO-loaded NPs selected formula and its combination with SP (BEO-NPs-SP) were investigated clinically for their effect against acne vulgaris after an appropriate in silico study. The optimum BEO-NPs-SP showed PS of 300.40 ± 22.56 nm, PDI of 0.571 ± 0.16, EE% of 87.89 ± 4.14%, and an acceptable ZP value of -29.7 ± 1.54 mV. Molecular modeling simulations showed the beneficial role of BEO constituents as supportive/connecting platforms for favored anchoring of SP on the Phosphatidylcholine (PC) interface. Clinical studies revealed significant improvement in the therapeutic response of BEO-loaded NPs that were combined with SP over BEO-NPs alone. In conclusion, the results proved the ability to utilize NPs as a successful nanovesicle for topical BEO delivery as well as the superior synergistic effect when combined with SP in combating acne vulgaris.

In Vivo Evaluation of Nanoemulsion Formulations for Metformin and Repaglinide Alone and Combination

Repaglinide and Metformin are used to treat Type 2 diabetes. Repaglinide with poor water solubility has relatively low oral bioavailability (56%) and undergoes hepatic first-pass metabolism. The oral bioavailability of metformin HCl is also low (about 50-60%). The purpose of this study was to prepare nanoemulsion formulations containing metformin HCl or repaglinide alone or in combination and characterize them in vitro and in vivo. Nanoemulsion formulations containing metformin HCl and/or repaglinide were successfully prepared and in vitro characterized. In addition, in vivo efficacy of nanoemulsion formulations was evaluated in a streptozotocin-nicotinamide-induced diabetic rat model. Biochemical, histopathological, and immunohistochemical evaluations were also performed. The mean droplet size and zeta potential values of nanoemulsion formulations were in the range of 110.15±2.64-120.23±2.16 nm and -21.95 – -24.33 mV, respectively. The percent entrapment efficiency values of nanoemulsion formulations were in the range of 93.600%-96.152%. All nanoemulsion formulations had a PDI of ≤0.223. A statistically significant decrease was observed in the blood glucose values of the diabetic rats treated with nanoemulsion formulations containing active substance/substances, compared to diabetic rats (control) (p<0.05). Nanoemulsion formulations (especially nanoemulsion containing metformin HCl and repaglinide combination) have a better antidiabetic activity and are more effective in reducing oxidative stress caused by diabetes.

Optimization of Nasal Liposome Formulation of Venlafaxine Hydrochloride using a Box-Behnken Experimental Design

Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes are biocompatible carriers that enhance transport qualities over the nasal mucosa. This research aimed to develop, formulate, characterize, and observe the prepared formulation. The formulation was developed using the thin-film hydration technique. The response surface plot interrelationship between three independent variables are lipid, cholesterol and polymer and four dependent variables such as particle size, percentage entrapment efficiency, and percentage drug release were ascertained using the Box-Behnken design. The drug-release chitosan-coated liposomes were reported to have a particle size distribution, entanglement efficiency, and 84%, respectively, of 191 ± 34.71 nm, 94 ± 2.71% and 94 ± 2.71%. According to in vitro investigations, liposomes as a delivery system for the nasal route provided a more sustained drug release than the oral dosing form. The intranasal administration of venlafaxine liposomal vesicles effectively enhanced the absolute bioavailability, retention time, and brain delivery of venlafaxine.

‘Poly phenolic phytoceutical loaded nano-bilosomes for enhanced caco-2 cell permeability and SARS-CoV 2 antiviral activity’: in-vitro and insilico studies

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predisposed to the emergence of worldwide catastrophe that impels the evolution of safe and effective therapeutic system. Polyphenols as resveratrol (RSV) exhibit a well evidenced antiviral activity. Unfortunately, like most phenolic nutraceuticals, RSV suffers from restrained solubility and massive degradation in GIT and liver which in turn prohibit its clinical use. Herein, PEGylated bilosomes (PBs) contain PEGylated edge activator along with the traditional components as (Span 60, cholesterol and bile salts) were proposed to boost both permeability and bioavailability of RSV. The investigation of the prominent effect of the diverse variables on the characteristics of the vesicles and picking of the optimum formula were conducted via construction of 23 factorial experiment. The appraisal of the formulae was conducted on the basis of entrapment efficiency percent (EE%), particle size (PS) and zeta potential (ZP). In addition, the spherical shaped optimal formula (F5) exhibited EE% of 86.1 ± 2.9%, PS of 228.9 ± 8.5 nm, and ZP of −39.8 ± 1.3 mV. The sorted optimum formula (F5) exhibited superior dissolution behaviors, and boosted Caco-2 cells cellular uptake by a round 4.7 folds relative to RSV dispersion. In addition, F5 demonstrated a complete in vitro suppression of SARS-CoV-2 at a concentration 0.48 μg/ml with 6.6 times enhancement in antiviral activity relative to RSV dispersion. The accomplished molecular modeling heavily provided proof for the possible interactions of resveratrol with the key residues of the SARS-CoV2 Mpro enzyme. Finally, F5 could be proposed as a promising oral panel of RSV for curation from SARS-CoV-2 infection.

Formulation and characterization of lamotrigine nasal insert targeted brain for enhanced epilepsy treatment

Lamotrigine. (LMT) is a triazine drug has an antiepileptic effect but with low water solubility, dissolution rate and thus therapeutic effect. Spanlastics are nano-vesicular carriers’ act as site-specific drug delivery system. Intranasal route could direct the drug from nose to brain and provide a faster and more specific therapeutic effect. Therefore, this study aimed to upload lamotrigine onto nano-vesicles using spanlastic nasal insert delivery for effective epilepsy treatment via overcoming lamotrigine’s low solubility and improving its bioavailability. Lamtrigine-loaded nano-spanlastic vesicles were prepared by ethanol injection method. To study different formulation factor’s effect on formulations characters; particle size (PS), Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency percentage (EE%) and LMT released amount after 6 h (Q6h); 2^1 and 3^1 full factorial designs were employed. Optimized formula was loaded in lyophilized nasal inserts formulation which were characterized for LMT release and mucoadhesion. Pharmacokinetics studies in plasma and brain were performed on rats to investigate drug targeting efficiency. The optimal nano-spanlastic formulation (F4; containing equal Span 60 amount (100 mg) and edge activator; Tween 80) exhibited nano PS (174.2 nm), high EE% (92.75%), and Q6h > 80%. The prepared nasal inserts (S4) containing 100 mg HPMC has a higher mucoadhesive force (9319.5 dyne/cm2) and dissolution rate (> 80% within 10 min) for rapid in vivo bio-distribution. In vivo studies showed considerable improvement brain and plasma’s rate and extent absorption after intranasal administration indicating a high brain targeting efficiency. The results achieved indicate that nano-spanlastic nasal-inserts offer a promising LMT brain targeting in order to maximize its antiepileptic effect.