Functional combination of resveratrol and tamoxifen to overcome tamoxifen-resistance in breast cancer cells.

Researchers are encountering challenges in addressing the issue of cancer cells becoming unresponsive to various chemotherapy treatments due to drug resistance. This study was designed to study the influence of antioxidant resveratrol (RSV) to sensitize resistant breast cancer (BC) cells toward tamoxifen (TAM). The cytotoxic effects of RSV and TAM against TAM-resistant LCC2 cells and their parental michigan cancer foundation-7 BC cells were determined by sulphorhodamine B assay. Further, the expression levels of multidrug resistance (MDR) genes including ABCB1, ABCC2, ABCG2, and MRP1 using quantitative polymerase chain reaction, apoptosis induction, and reactive oxygen species (ROS) content using flow cytometry were evaluated in either LCC2 cells treated with RSV, TAM, or their combination. The obtained results showed that resistant cells have a magnificent level of MDR genes. This elevated expression dramatically lowered upon receiving the combined therapy of RSV and TAM. Additionally, our work assessed the possible role of RSV in modulating the expression of MDR genes by controlling the expression of certain microRNAs (miRNAs) that target ATP-binding cassette (ABC) transporters. According to the obtained data, the TAM and RSV combination increased the expression of tumor inhibitor miRNAs such miR-10b-3p, miR-195-3p, and miR-223-3p, which made LCC2 cells more sensitive to TAM. Furthermore, this combination showed an elevation in apoptotic levels and total ROS content. The combination between RSV and TAM could be a functional therapy in the fight against TAM-resistant BC cells via modulating miRNA and ABC transporters.

Fabrication of gastro-floating sustained-release etoricoxib and famotidine tablets: design, optimization, in-vitro, and in-vivo evaluation.

In this study, a new gastro-floating sustained-release tablet (GFT) with a combination of Etoricoxib (ET) and Famotidine (FM) was successfully developed. GFTs were prepared by using a combination of hydrophilic swellable natural/semi-synthetic polymers as a controlled-release layer. Through a 24 full factorial statistical experimental design, the effects of formulation factors on the release of GFTs were conducted. The ideal floating tablet (FT) comprised konjac-gum (150 mg), guar-gum (26.57 mg), xanthan-gum (54.17 mg), and HPMC-K15-M (69.25 mg). The ideal FT exhibited a high swelling index (SI) (297.7%) and rapid FLT (around 50 s) in 0.1 N HCl as well as controlled release of ET (22.43% in 1 h and 77.47% in 8 h) and FM (24.89% in 1 h and 93.82% in 8 h) with the absence of any drug-excipient interactions. The AUC0∼72 (ng h/mL) of ET and FM in the GFTs were approximately double-fold of the market, respectively. The relative bioavailability was (207.48 ± 12.02% and 208.51 ± 13.11%) compared with commercial tablets. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. These findings revealed the successful preparation of the sustained-release floating tablet with improved dual drug delivery.

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.

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.

Comparative evaluation on the effect of different cavity disinfectant nano gels; Chlorohexidine, Propolis, Liquorice versus Diode Laser in terms of composite microleakage (comparative in vitro study).

INTRODUCTION: The application of different cavity disinfectants is an essential step that eliminates bacteria after cavity preparation. However, some of these materials may affect restoration sealing ability. AIM: This study aimed to assess the degree of microleakage at the tooth restoration interface after using different nano prepared cavity disinfectants versus Diode Laser. MATERIALS AND METHODS: Three disinfectants were prepared on the nanoscale; Propolis, Liquorice and Chlorhexidine. A total of 40 extracted premolars with standard class V cavities were prepared on the facial surface. Teeth were divided into five groups according to the applied cavity disinfection protocol; no treatment, Chloehexidine, Propolis, Liquorice, and Diode Laser. After application of composite resin restoration, all teeth were subjected to thermocycling, afterwords the degree of microleakage was measured in micrometers. Data were analyzed by one-way analysis of variance (ANOVA) test, followed by Bonferroni's and Tukey's post hoc test. RESULTS: The highest mean microlekage value was recorded in no treatment group, followed by Liquorice, Propolis. While Diode Laser group showed the lowest degree of microleakage. CONCLUSION: Diode Laser cavity disinfectant has no negative effect on the restoration sealing ability. Nano prepared Propolis showed comparative results to nanoChloehexidine as both had low degree of microleakage.

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.

Enhance the oral insulin delivery route using a modified chitosan-based formulation fabricated by microwave.

Chitosan (Cs) was subjected to ball milling and subsequently functionalized with Dinitro salicylic acid (Cs-DNS) to enhance the efficacy of oral insulin delivery. The hydrodynamic spherical particle sizes exhibited 33.29 ± 5.08 nm for modified Cs-DNS NPs. Irrespective of insulin entrapment, zeta potential measurements revealed positively charged Cs-DNS NPs (+ 35 ± 3.5 mV). The entrapment performance (EP%) was evaluated in vitro, and insulin release patterns at various pH levels. The EP% for Cs-DNS NPs was 99.3 ± 1.6. Cs- DNS NPs retained a considerable amount of insulin (92 %) in an acidic medium, and significant quantities were released at increasing pH values over time. In vivo investigations, the diabetic rats which taken insulin-incorporated NPs had lower serum glucose levels (SGL) after 3 h to (39.4 ± 0.6 %) for Cs- DNS NPs. For insulin-incorporated Cs- DNS NPs, the bioavailability (BA%) and pharmacological availability (PA%) were 17.5 ± 0.31 % and 8.6 ± 0.8 %, respectively. The assertion above highlights the significance and effectiveness of modified chitosan in promoting insulin delivery, decreasing SGL levels, and guaranteeing safety.

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.

Merging konjac glucomannan with other copolymeric hydrogels as a cutting-edge liquid raft system for dual delivery of etoricoxib and famotidine.

This study aimed to formulate and evaluate a floating raft system for the co-delivery of etoricoxib (ETO) and famotidine (FAM) using a combination of glucomannan with natural/semi-synthetic polysaccharides. Formulation variables affect gelation lag time (GLT), floating lag time (FLT), and release percentage of drugs after 1-8 h, Stability, and viscosity parameters were evaluated. In vivo X-ray studies, followed by the pharmacokinetic study, were performed on human volunteers. Formulations exhibited pseudoplastic behavior for ease of swallowing. The optimum raft system (ORS) comprised 1% Na alginate, 0.1% Low Methoxyl (LM) pectin, 0.8% Konjac glucomannan (KGL), 1% Precirol, and 1% CaCO3. ORS exhibited rapid GLT and FLT (around 42 and 8 sec respectively) in 0.1 N HCl as well as controlled release of ETO (15% in 1 h and 82% in 8 h) and FAM (29% in 1 h and 85% in 8 h). Formulation stability with the absence of any drug-excipient interactions was observed. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. Compared with marketed products, ORS showed superior relative bioavailability for both drugs. These findings revealed the successful preparation of a promising raft system with improved dual drug delivery.

One-pot microwave synthesis of chitosan-stabilized silver nanoparticles entrapped polyethylene oxide nanofibers, with their intrinsic antibacterial and antioxidant potency for wound healing.

Different physical and chemical techniques could be used to prepare chitosan/Silver nanoparticle (CHS/AgNPs) nanocomposite. The microwave heating reactor was rationally adopted as a benign tool for preparing CHS/AgNPs owing to less energy consumption and shorter time required for completing the nucleation and growth particles. UV-Vis, FTIR, and XRD, provided conclusive evidence of the AgNPs creation, while TEM micrographs elucidated that the size was spherical (20 nm). CHS/AgNPs were embedded in polyethylene oxide (PEO) nanofiber via electrospinning, and their biological properties, cytotoxicity evaluation, antioxidant, and antibacterial activity assays were investigated. The generated nanofibers have mean diameters of 130.9 ± 9.5, 168.7 ± 18.8, and 186.8 ± 8.19 nm for PEO, PEO/ CHS, and PEO/ CHS (AgNPs), respectively. Because of the tiny AgNPs particle size loaded in PEO/CHS (AgNPs) fabricated nanofiber, good antibacterial activity with ZOI against E. coli was 51.2 ± 3.2, and S. aureus was 47.2 ± 2.1 for PEO/ CHS (AgNPs) nanofibers. Non-toxicity was observed against Human Skin Fibroblast and Keratinocytes cell lines (>93.5 %), which justifies its great antibacterial potential to remove or prevent infection in wounds with fewer adverse effects.

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.

Fabrication of nanostructured lipid carriers ocugel for enhancing Loratadine used in treatment of COVID-19 related symptoms: statistical optimization, in-vitro, ex-vivo, and in-vivo studies evaluation.

Loratadine (LORA), is a topical antihistamine utilized in the treatment of ocular symptoms of COVID-19. The study aimed to develop a Loratadine Nanostructured Lipid Carriers Ocugel (LORA-NLCs Ocugel), enhance its solubility, trans-corneal penetrability, and bioavailability. full-factorial design was established with 24 trials to investigate the impact of several variables upon NLCs properties. LORA-NLCs were fabricated by using hot melt emulsification combined with high-speed stirring and ultrasonication methods. All obtained formulae were assessed in terms of percent of entrapment efficiency (EE%), size of the particle (PS), zeta potential (ZP), as well as in-vitro release. Via using Design Expert® software the optimum formula was selected, characterized using FTIR, Raman spectroscopy, and stability studies. Gel-based of optimized LORA-NLCs was prepared using 4% HPMC k100m which was further evaluated in terms of physicochemical properties, Ex-vivo, and In-vivo studies. The optimized LORA-NLCs, comprising Compritol 888 ATO®, Labrasol®, and Span® 60 showed EE% of 95.78 ± 0.67%, PS of 156.11 ± 0.54 nm, ZP of -40.10 ± 0.55 Mv, and Qh6% of 99.67 ± 1.09%, respectively. Additionally, it illustrated a spherical morphology and compatibility of LORA with other excipients. Consequently, gel-based on optimized LORA-NLCs showed pH (7.11 ± 0.52), drug content (98.62%± 1.31%), viscosity 2736 cp, and Q12% (90.49 ± 1.32%). LORA-NLCs and LORA-NLCs Ocugel exhibited higher ex-vivo trans-corneal penetrability compared with the aqueous drug dispersion. Confocal laser scanning showed valuable penetration of fluoro-labeled optimized formula and LORA-NLCs Ocugel through corneal. The optimized formula was subjected to an ocular irritation test (Draize Test) that showed the absence of any signs of inflammation in rabbits, and histological analysis showed no effect or damage to rabbit eyeballs. Cmax and the AUC0-24 were higher in LORA-NLCs Ocugel compared with pure Lora dispersion-loaded gel The research findings confirmed that NLCs could enhance solubility, trans-corneal penetrability, and the bioavailability of LORA.

Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies.

Colorectal cancer (CRC) is considered one of the most commonly diagnosed malignant diseases. Recently, there has been an increased focus on using nanotechnology to resolve most of the limitations in conventional chemotherapy. Niosomes have great advantages that overcome the drawbacks associated with other lipid drug delivery systems. They are simple, cheap, and highly stable nanocarriers. This study investigated the effectiveness of using niosomes with their amphiphilic characteristics in the incorporation of both hydrophilic and hydrophobic anticancer drugs for CRC treatment. METHODS: Drug-free niosomes were formulated using a response surface D-optimal factorial design to study the cholesterol molar ratio, surfactant molar ratio and surfactant type effect on the particle size and Z-potential of the prepared niosomes. After numerical and statistical optimization, an optimized formulation having a particle size of 194.4 ± 15.5 nm and a Z-potential of 31.8 ± 1.9 mV was selected to be loaded with Oxaliplatin and Paclitaxel separately in different concentrations. The formulations with the highest entrapment efficiency (EE%) were evaluated for their drug release using the dialysis bag method, in vitro antitumor activity on HT-29 colon cancer cell line and apoptosis activity. RESULTS: Niosomes prepared using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at a molar ratio 4, cholesterol (2 molar ratio) and loaded with 1 molar ratio of either Oxaliplatin or Paclitaxel provided nanosized vesicles (278.5 ± 19.7 and 251.6 ± 18.1 nm) with a Z-potential value (32.7 ± 1.01 and 31.69 ± 0.98 mV) with the highest EE% (90.57 ± 2.05 and 93.51 ± 2.97) for Oxaliplatin and Paclitaxel, respectively. These formulations demonstrated up to 48 h drug release and increased the in vitro cytotoxicity and apoptosis efficiency of both drugs up to twice as much as free drugs. CONCLUSION: These findings suggest that different formulation composition parameters can be adjusted to obtain nanosized niosomal vesicles with an accepted Z-potential. These niosomes could be loaded with either hydrophilic drugs such as Oxaliplatin or hydrophobic drugs such as Paclitaxel. Drug-loaded niosomes, as a unique nanomicellar system, could enhance the cellular uptake of both drugs, resulting in enhanced cytotoxic and apoptosis effects against HT-29 colon cancer cells. Oxaliplatin-niosomes and Paclitaxel-niosomes can be considered promising alternative drug delivery systems with enhanced bioavailability of these two anticancer drugs for colorectal cancer treatment.

Three waves changes, new variant strains, and vaccination effect against COVID-19 pandemic.

It has been more than one year since the first case of the coronaviruses was infected by COVID-19 in China. The world witnessed three waves of the corona virus till now, and more upcoming is expected, whereas several challenges are presented. Empirical data displayed that the features of the virus effects do vary between the three periods. The severity of the disease, differences in symptoms, attitudes of the people have been reported, although the comparative characteristics of the three waves still keep essentially indefinite. In contrast, the sense of danger toward the cries gradually decreases in most countries. This may be due to some factors, including the approved vaccines, introducing alternative plans from politicians to control and deal with the epidemic, and decreasing the mortality rates. However, the alarm voice started to rise again with the appearance of new variant strains with several mutations in the virus. Several more questions began to be asked without sufficient answers. Mutations in COVID-19 have introduced an extreme challenge in preventing and treating SARS-COV-2. The essential feature for mutations is producing new variants known by high tensmibility, disturbing the viral fitness, and enhancing the virus replication. One of the variants that has emerged recently is the Delta variant (B.1.617.2), which was firstly detected in India. In November 2021, a more ferocious mutant appeared in South Africa, also called omicron (B.1.1.529). These mutants grabbed world attention because of their higher transmissibility than the progenitor variants and spread rapidly. Several information about the virus are still confusing and remains secret. There are eight approved vaccines in the market; however, the investigation race about their effect against reinfection and their role against the new variants is still under investigation. Furthermore, this is the first time vaccinating against COVID-19, so the question remains: Will we need an annual dose of the corona vaccines, and the side effects don't been observed till now?

Transdermal Delivery of Telmisartan: Formulation, in vitro, ex vivo, Iontophoretic Permeation Enhancement and Comparative Pharmacokinetic Study in Rats.

PURPOSE: The purpose of this study was to prepare telmisartan transethosomes, incorporate them into a gel, evaluate them for in vitro drug release and in vivo permeation using iontophoresis to enhance their transdermal delivery. MATERIALS AND METHODS: TE formulae were prepared using various surfactants (SAAs), different ethanol concentrations, and different phospholipid-to-SAA ratios with different cholesterol ratios, characterized according to their entrapment efficiency percentage (EE%), zeta potential (ZP), particle size (PS), and polydispersity index (PDI). The optimum three formulae were incorporated into a gel, evaluated physically, in vitro dissolution, and ex vivo drug permeation using rat skin and Iontophoresis was performed on the best formula. RESULTS: The optimum three formulae (F29, F31, F32) had an EE% of 97±0.26%, 89±0.25% and 88±0.17%, PS of 244±5.88 nm, 337±4.6 nm and 382.2±3.06 nm, PDI of 0.57±1.9, 0.5±1.4 and 0.63±2.2 and ZP of -31.6±1.59 mV, -28.3±3.79 mV and -31±5.65, respectively. Selecting F29 for in vivo study by iontophoretic enhancement, Cmax was increased by 1.85 folds compared to the commercial oral tablet and by 1.5 folds compared to transdermal gel. Tmax decreased by half using iontophoresis compared to commercial tablets and transdermal gel. CONCLUSION: The transethosomal formulation of telmisartan enhanced its transdermal absorption and increased its bioavailability as well. Iontophoresis was used to increase maximum plasma concentration and reduce Tmax by half.

Formulation and Evaluation of Baclofen-Meloxicam Orally Disintegrating Tablets (ODTs) Using Co-Processed Excipients and Improvement of ODTs Performance Using Six Sigma Method.

PURPOSE: This study aimed to formulate an orally disintegrating tablet (ODT) containing both baclofen and meloxicam together for treating osteoarthritis. METHODS: Direct compression method was used to prepare ODTs using three types of co-processed excipients (Prosolv ODT G2®, F-melt®, and Pharmaburst®500). ODTs were evaluated according to weight variation, thickness, friability, hardness, drug content, wetting time, in-vitro disintegration time, in-vitro dissolution test, and palatability. To enhance the in-vitro dissolution of meloxicam and palatability of ODT, a six sigma methodology was used, and an improvement phase was established where ODTs were prepared using lyophilization and levigation techniques. Finally, a pharmacokinetic study of the improved ODT was accomplished in comparison to the conventional oral tablet. RESULTS: Pharmaburst-based formula (F4) showed the shortest wetting time and, consequently, the shortest disintegration time and the highest percentage of drug dissolved within 3 min compared to the other formulae. All the improved ODTs had a bitterness taste score vary from (0) palatable and (+1) tasteless. The current sigma level was 3.628 σ and 3.33 σ for palatability and solubility of ODT, respectively, which indicated the process was successfully improved compared with the previous sigma level of 2.342 σ of both processes. Pharmacokinetic study of the improved ODTs showed a significant decrease of Tmax to 120 and 30 min instead of 180 and 120 min for meloxicam and baclofen, respectively. CONCLUSION: ODTs were successfully improved using the six sigma methodology, the pharmacokinetic parameters of both drugs were enhanced due to rapid absorption through the oral mucosa.

Chitosan for biomedical applications, promising antidiabetic drug delivery system, and new diabetes mellitus treatment based on stem cell.

Since chitosan's excellent pharmacokinetic and chemical properties, it is an attractive and promising carbohydrate biopolymer in biomedical applications. Chitosan's beneficial function in the defense and propagation of pancreatic ß cells, reducing hyperglycemia, and avoiding diabetes mellitus associated with impaired lipid metabolism has been demonstrated in several studies. Additionally, chitosan has also been used in various nanocarriers to deliver various antidiabetic drugs to reduce glucose levels. Herein, the first to provide the currently available potential benefits of chitosan in diabetes mellitus treatment focuses on chitosan-based nanocarriers for oral administration of various antidiabetic drugs nasal and subcutaneous passages. Moreover, chitosan is used to activate and deliver stem cells and differentiate them into cells similar to pancreatic beta cells as a new type of treatment for type one diabetes mellitus. The results of this review will be helpful in the development of promising treatments and better control of diabetes mellitus.

Formulation and Characterization of Acetazolamide/Carvedilol Niosomal Gel for Glaucoma Treatment: In Vitro, and In Vivo Study.

Acetazolamide (ACZ) is a diuretic used in glaucoma treatment; it has many side effects. Carvedilol (CAR) is a non-cardioselective beta-blocker used in the treatment of elevated intraocular pressure; it is subjected to the first-pass metabolism and causes fluids accumulation leading to edema. This study focuses on overcoming previous side effects by using a topical formula of a combination of the two previous drugs. Sixty formulations of niosomes containing Span 20, Span 60, Tween 20, and Tween 60 with two different ratios were prepared and characterized. Formulation with the lowest particle size (416.30 ± 0.23), the highest zeta potential (72.04 ± 0.43 mv), and the highest apparent coefficient of corneal permeability (0.02 ± 0.29 cm/h) were selected. The selected formula was incorporated into the gel using factorial design 23. Niosomes (acetazolamide/carvedilol) consisting of Span 60 and cholesterol in the molar ratio (7:6), HMPC, and carbopol with two different ratios were used. The selected formula was subjected to an in vivo study of intraocular pressure in ocular hypertensive rabbits for 60 h. The sustained gel formula of the combination decreased (IOP) to normal after 1 h and sustained efficacy for 4 days. Histological analysis of rabbit eyeballs treated with the selected formula showed improvement in glaucomatous eye retinal atrophy.

Development, Characterization, and in-vivo Pharmacokinetic Study of Lamotrigine Solid Self-Nanoemulsifying Drug Delivery System.

PURPOSE: This study aimed to prepare solid self-nanoemulsified drug delivery system (S-SNEDDS) of lamotrigine (LMG) for enhancing its dissolution and oral bioavailability (BA). METHODS: Nineteen liquid SNEDDS were prepared (R1-R19) using D-optimal design with different ratios of oil, surfactant (S), and cosurfactant (Cos). The formulations were characterized regarding robustness to dilution, droplet size, thermodynamic stability testing, self-emulsification time, in-vitro release in 0.1 N HCl and phosphate buffer (PB; pH 6.8). Design Expert® 11 software was used to select the optimum formulations. Eight S-SNEDDS were prepared (S1-S8) using 23 factorial design, and characterized by differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and scanning electron microscopy (SEM). The optimum formulation was chosen regarding in-vitro drug released in 0.1 N HCl and PB, compared to pure LMG and commercial tablet (Lamictal®). The BA of LMG from the optimized S-SNEDDS formulation was evaluated in rabbits compared to pure LMG and Lamictal®. RESULTS: The optimized S-SNEDDS was S2, consisting of R9 adsorbed on Aeroperl® 300 in a ratio of 1:1, with the best results regarding in-vitro drug released in 0.1 N HCl at 15 min (100%) compared to pure LMG (73.40%) and Lamictal® (79.43%), and in-vitro drug released in PB at 45 min (100%) compared to pure LMG (30.46%) and Lamictal® (92.08%). DSC, PXRD, and SEM indicated that LMG was molecularly dispersed within the solid nano-system. The BA of S2 was increased 2.03 and 1.605 folds compared to pure LMG, and Lamictal®, respectively. CONCLUSION: S2 is a promising S-SNEDDS formulation. It can be a potential carrier for improving dissolution, and BA of LMG.