Identifying and validating MMP family members (MMP2, MMP9, MMP12, and MMP16) as therapeutic targets and biomarkers in kidney renal clear cell carcinoma (KIRC).

Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.

Preparation, In Vitro Characterization, and Evaluation of Polymeric pH-Responsive Hydrogels for Controlled Drug Release.

The purpose of the current research is to formulate a smart drug delivery system for solubility enhancement and sustained release of hydrophobic drugs. Drug solubility-related challenges constitute a significant concern for formulation scientists. To address this issue, a recent study focused on developing PEG-g-poly(MAA) copolymeric nanogels to enhance the solubility of olmesartan, a poorly soluble drug. The researchers employed a free radical polymerization technique to formulate these nanogels. Nine formulations were formulated. The newly formulated nanogels underwent comprehensive tests, including physicochemical assessments, dissolution studies, solubility evaluations, toxicity investigations, and stability examinations. Fourier transform infrared (FTIR) investigations confirmed the successful encapsulation of olmesartan within the nanogels, while thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies verified their thermal stability. Scanning electron microscopy (SEM) images revealed the presence of pores on the surface of the nanogels, facilitating water penetration and promoting rapid drug release. Moreover, powder X-ray diffraction (PXRD) studies indicated that the prepared nanogels exhibited an amorphous structure. The nanogel carrier system led to a significant enhancement in olmesartan's solubility, achieving a remarkable 12.3-fold increase at pH 1.2 and 13.29-fold rise in phosphate buffer of pH 6.8 (NGP3). Significant swelling was observed at pH 6.8 compared to pH 1.2. Moreover, the formulated nexus is nontoxic and biocompatible and depicts considerable potential for delivery of drugs and protein as well as heat-sensitive active moieties.

Utilizing sinapic acid as an inhibitory antiviral agent against MERS-CoV PLpro.

Concerns about the social and economic collapse, high mortality rates, and stress on the healthcare system are developing due to the coronavirus onslaught in the form of various species and their variants. In the recent past, infections brought on by coronaviruses severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) as well as middle east respiratory syndrome coronavirus (MERS-CoV) have been reported. There is a severe lack of medications to treat various coronavirus types including MERS-CoV which is hazard to public health due to its ability for pandemic spread by human-to-human transmission. Here, we utilized sinapic acid (SA) against papain-like protease (PLpro), a crucial enzyme involved in MERS-CoV replication, because phytomedicine derived from nature has less well-known negative effects. The thermal shift assay (TSA) was used in the current study to determine whether the drug interact with the recombinant MERS-CoV PLpro. Also, inhibition assay was conducted as the hydrolysis of fluorogenic peptide from the Z-RLRGG-AMC-peptide bond in the presence of SA to determine the level of inhibition of the MERS-CoV PLpro. To study the structural binding efficiency Autodock Vina was used to dock SA to the MERS-CoV PLpro and results were analyzed using PyMOL and Maestro Schrödinger programs. Our results show a convincing interaction between SA and the MERS protease, as SA reduced MERS-CoV PLpro in a dose-dependent way IC50 values of 68.58 µM (of SA). The TSA showed SA raised temperature of melting to 54.61 °C near IC50 and at approximately 2X IC50 concentration (111.5 µM) the Tm for SA + MERS-CoV PLpro was 59.72 °C. SA was docked to MERS-CoV PLpro to identify the binding site. SA bound to the blocking loop (BL2) region of MERS-CoV PLpro interacts with F268, E272, V275, and P249 residues of MERS-CoV PLpro. The effectiveness of protease inhibitors against MERS-CoV has been established and SA is already known for broad range biological activity including antiviral properties; it can be a suitable candidate for anti-MERS-CoV treatment.

Characterizing EBV-associated Gastric Carcinoma (EBVaGC): A deep dive into LMP1 expression patterns.

Gastric cancer (GC) is a serious public health issue due to its frequency and severity. It is, for both sexes, one of the most common causes of cancer-related death and is a major contributor to the global burden of disease. Recent data show that Epstein-Barr virus (EBV) has been detected in different histopathological subtypes of gastric carcinoma and that EBV-associated gastric carcinoma (EBVaGC) represents about 10% of all cases. Moreover, the LMP1 protein characterizing the malignant transformation of cells in several cancer models seems to be very rarely expressed in this type of cancer. This study aimed to characterize EBVaGC in our population by detecting LMP1 in gastric carcinomas in about 30 selected patients. The results showed that in our population, nuclear staining predominates, showing that the antrum remains the most sampled site both for these pathologies and for LMP1 positivity (nuclear staining). In general, the LMP1 marking was negative for 22.58%, positive with a nuclear predominance at 64.52%, nuclear and cytoplasmic at 12.90%, and no positive marking for the cytoplasm. Results were not like the different studies on the expression of this oncogenic protein without EBVsCG, probably finding an explanation in the fact that our country is among the endemic regions for this herpes virus. In conclusion, the rate of LMP1 expression among gastric carcinomas does not seem similar to that observed in other countries. This study characterizing EBVaGC in Tizi-Ouzou, Algeria, reinforces the need for further studies to clarify the role of EBV (LMP1) and to explore its potential value as a predictive biomarker for the development of this type of cancer pathology.

Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies.

Bromocriptine mesylate (BM), primarily ergocryptine, is a dopamine agonist derived from ergot alkaloids. This study aimed to formulate chitosan (CS)-coated poly ε-caprolactone nanoparticles (PCL NPs) loaded with BM for direct targeting to the brain via the nasal route. PCL NPs were optimized using response surface methodology and a Box-Behnken factorial design. Independent formulation parameters for nanoparticle attributes, including PCL payload (A), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) concentration (B), and sonication time (C), were investigated. The dependent variables were nanoparticle size (Y1), zeta potential (Y2), entrapment efficiency (EE; Y3), and drug release rate (Y4). The optimal formulation for BM-PCL NPs was determined to be 50 mg PCL load, 0.0865% TPGS concentration, and 8 min sonication time, resulting in nanoparticles with a size of 296 ± 2.9 nm having a zeta potential of -16.2 ± 3.8 mV, an EE of 90.7 ± 1.9%, and a zero-order release rate of 2.6 ± 1.3%/min. The optimized BM-PCL NPs were then coated with CS at varying concentrations (0.25, 0.5, and 1%) to enhance their effect. The CS-PCL NPs exhibited different particle sizes and zeta potentials depending on the CS concentration used. The highest EE (88%) and drug load (DL; 5.5%) were observed for the optimized BM-CS-PCL NPs coated with 0.25% CS. The BM-CS-PCL NPs displayed a biphasic release pattern, with an initial rapid drug release lasting for 2 h, followed by a sustained release for up to 48 h. The 0.25% CS-coated BM-CS-PCL NPs showed a high level of permeation across the goat nasal mucosa, with reasonable mucoadhesive strength. These findings suggested that the optimized 0.25% CS-coated BM-CS-PCL NPs hold promise for successful nasal delivery, thereby improving the therapeutic efficacy of BM.

Box-Behnken Design for Assessing the Efficiency of Aflatoxin M1 Detoxification in Milk Using Lactobacillus rhamnosus and Saccharomyces cerevisiae.

Milk contaminated with aflatoxin can lead to liver cancer. Aflatoxin B1 (AFB1), a serious animal feed contaminant, is transformed into Aflatoxin M1 (AFM1) and secreted in milk. In this study, a biological method using probiotic bacteria, Lactobacillus rhamnosus (L. rhamnosus) in combination with Saccharomyces cerevisiae (S. cerevisiae), was used to assess their antiaflatoxigenic effect in animal milk. A Box-Behnken design was used to establish the optimal ratio of L. rhamnosus and S. cerevisiae, incubation time, and temperature for efficient AFM1 detoxification from milk. To achieve this, the primary, interaction, and quadratic effects of the chosen factors were investigated. To investigate the quadratic response surfaces, a second-order polynomial model was built using a three-factor, three-level Box-Behnken design. The quantity of AFM1 was detected by the ELISA technique. The results of these experiments obtained an optimum condition in AFM1 detoxification of the three tested factors in order to maximize their effect on AFM1 detoxification in milk. The model was tested in three highly contaminated milk samples to assure the efficacy of the model. AFM1 detoxification was up to 98.4% in contaminated milk samples. These promising results provide a safe, low-cost, and low-time-consuming solution to get rid of the problem of milk contamination with AFM1.

Assembly of nanostructured lipid carriers loaded gefitinib and simvastatin as hybrid therapy for metastatic breast cancer: Codelivery and repurposing approach.

Breast cancer represents a life-threatening problem globally. The major challenge in the clinical setting is the management of cancer resistance and metastasis. Hybrid therapy can affect several cellular targets involved in carcinogenesis with a lessening of adverse effects. Therefore, the current study aims to assemble, and optimize a hybrid of gefitinib (GFT) and simvastatin (SIM)-loaded nanostructured lipid carrier (GFT/SIM-NLC) to combat metastatic and drug-resistant breast cancer. GFT/SIM-NLC cargos were prepared using design of experiments to investigate the impact of poloxamer-188 and fatty acids concentrations on the physicochemical and pharmaceutical behavior properties of NLC. Additionally, the biosafety of the prepared GFT/SIM-NLC was studied using a fresh blood sample. Afterward, the optimized formulation was subjected to an MTT assay to study the cytotoxic activity of GFT/SIM-NLC compared to free GFT/SIM using an MCF-7 cell line as a surrogate model for breast cancer. The present results revealed that the particle size of the prepared NLC ranged from (209 to 410 nm) with a negative zeta potential value ranging from (-17.2 to -23.9 mV). Moreover, the optimized GFT/SIM-NLC formulation showed favorable physicochemical properties and promising lymphatic delivery cargos. A biosafety study indicates that the prepared NLC has a gentle effect on erythrocyte hemolysis. Cytotoxicity studies revealed that GFT/SIM-NLC enhanced the killing of the MCF-7 cell line compared to free GFT/SIM. This study concluded that the hybrid therapy of GFT/SIM-NLC is a potential approach to combat metastatic and drug-resistant breast cancer.

Suppression of Nasopharyngeal and Gastric Tumor Growth in a Mouse Model by Antibodies to Epstein-Barr Virus LMP1 Protein.

The study aimed to investigate the antitumor efficacy of anti-LMP1 antibodies in EBV-positive nasopharyngeal and stomach cell lines and xenograft models. The study also examined the NF-κB expression and cell cycle activation of NPC-serum-exosome-associated LMP1. Anti-LMP1 antibody treatment before or during cell implantation prevented tumor growth in nude mice. A small dose of antibodies resulted in complete tumor regression for at least three months after the tumors had grown in size. The consumption of antigen-antibody complexes by tumor cells limited tumor growth. In vitro experiments showed that anti-LMP1 antibodies killed EBV-positive NPC- or GC-derived epithelial cell lines and EBV-positive human B-cell lines but not EBV-negative cell lines. Treatment with anti-LMP1 reduced NF-κB expression in cells. The animal model experiments showed that anti-LMP1 inhibited and prevented NPC- or GC-derived tumor growth. The results suggest that LMP1 antibody immunotherapy could cure nasopharyngeal cancer, EBV-positive gastric carcinoma, and EBV-associated lymphomas. However, further validation of these findings is required through human clinical trials.

Design and dermatokinetic appraisal of lornoxicam-loaded ultrafine self-nanoemulsion hydrogel for the management of inflammation: In vitro and in vivo studies.

The present study aimed to evaluate the impact of ultrafine nanoemulsions on the transdermal delivery of lornoxicam (LOR) for management of the inflammation. The transdermal administration of LORNE could increase the efficacy of LOR with a reduction in side effects. Merging the beneficial properties of ultrafine nanoemulsions and their components (penetration enhancers) can lead to good solubilization, a small droplet size, and more effective LOR carriers. Therefore, this study aims to develop and evaluate the potential use of ultrafine nanoemulsions of LOR (LORNE) to elucidate their skin targeting for the treatment of inflammation. Based on solubility and pseudo ternary phase diagram tests, ultrafine LORNE composed of Labrafil M 2125 CS, Cremophor RH40, and Transcutol HP to deliver LOR was developed and characterized for its physicochemical properties, emulsification, and in vitro release. The selected LORNE was incorporated into carbopol gel (LORNE-Gel) and examined for ex vivo skin permeation, retention, dermatokinetics, anti-inflammatory efficacy, and skin irritation. The selected LORNE12-Gel could improve skin permeation, retention, and dermatokinetic results significantly (p < 0.05) with enhanced CSkin max and AUC0-48h compared to LOR-Gel. Moreover, LORNE12-Gel showed a remarkable anti-inflammatory effect compared to LOR-Gel after topical application. No signs of skin irritation were observed following treatment, indicating the safety of LORNE12-Gel. Thus, this study demonstrated that LOR-loaded LORNE12-Gel could be promising as an efficient transdermal nanocarrier for an anti-inflammatory alternative.

Development and Optimization of Tamarind Gum-ß-Cyclodextrin-g-Poly(Methacrylate) pH-Responsive Hydrogels for Sustained Delivery of Acyclovir.

Acyclovir has a short half-life and offers poor bioavailability. Its daily dose is 200 mg five times a day. A tamarind gum and ß-cyclodextrin-based pH-responsive hydrogel network for sustained delivery of acyclovir was developed using the free-radical polymerization technique. Developed networks were characterized by FTIR, DSC, TGA, PXRD, EDX, and SEM. The effect of varying feed ratios of polymers, monomers, and crosslinker on the gel fraction, swelling, and release was also investigated. FTIR findings confirmed the compatibility of the ingredients in a new complex polymer. The thermal stability of acyclovir was increased within the newly synthesized polymer. SEM photomicrographs confirmed the porous texture of hydrogels. The gel fraction was improved (from 90.12% to 98.12%) with increased reactant concentrations. The pH of the dissolution medium and the reactant contents affected swelling dynamics and acyclovir release from the developed carrier system. Based on the R2 value, the best-fit model was zero-order kinetics with non-Fickian diffusion as a release mechanism. The biocompatibility of the developed network was confirmed through hematology, LFT, RFT, lipid profile, and histopathological examinations. No sign of pathology, necrosis, or abrasion was observed. Thus, a pH-responsive and biocompatible polymeric system was developed for sustained delivery of acyclovir to reduce the dosing frequency and improve patient compliance.

Development of a Novel Methotrexate-Loaded Nanoemulsion for Rheumatoid Arthritis Treatment with Site-Specific Targeting Subcutaneous Delivery.

Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease that causes disability due to progressive inflammation and destruction of the tissues around the joints. Methotrexate is mainly used to prevent the progression of joint destruction and reduce the deformity. The major challenge in treating RA with methotrexate is the systemic side effects that limit dose escalation. Hence, a novel formulation of a methotrexate-loaded nanoemulsion for subcutaneous administration was developed that aims to deliver methotrexate into the system via the lymph. The methotrexate-loaded nanoemulsion was prepared by using the aqueous-titration method. The prepared nanoemulsion was investigated for particle size, surface charge, surface morphology, entrapment efficiency, DSC (differential scanning colorimetry), drug release, hemocompatibility assay, and cytotoxicity, as well as anti-arthritic and stability studies. The vesicle size, zeta potential, PDI (polydispersity index), and entrapment efficiency of the optimized nanoemulsion were 87.89 ± 2.86 nm, 35.9 ± 0.73 mV, 0.27, and 87 ± 0.25%, respectively. The DSC study showed that the crystalline methotrexate was converted to an amorphous form and the drug was fully incorporated into the vesicles. After 72 h, the optimized nanoemulsion showed a drug release of 96.77 ± 0.63%, indicating a sustained-release dosage form. Cytocompatibility testing by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay on macrophage cell lines showed that the nanoemulsion was non-toxic. The formulation showed significant anti-arthritic activity compared to the marketed drug solution. In addition, the nanoemulsion containing methotrexate remained stable for three months when stored at a low temperature. Since the nanoemulsion containing methotrexate has excellent physicochemical properties and lowers systemic side effects by targeted delivery, it is a desirable technology for subcutaneous drug delivery.

Unique Properties of Surface-Functionalized Nanoparticles for Bio-Application: Functionalization Mechanisms and Importance in Application.

This review tries to summarize the purpose of steadily developing surface-functionalized nanoparticles for various bio-applications and represents a fascinating and rapidly growing field of research. Due to their unique properties-such as novel optical, biodegradable, low-toxicity, biocompatibility, size, and highly catalytic features-these materials are considered superior, and it is thus vital to study these systems in a realistic and meaningful way. However, rapid aggregation, oxidation, and other problems are encountered with functionalized nanoparticles, inhibiting their subsequent utilization. Adequate surface modification of nanoparticles with organic and inorganic compounds results in improved physicochemical properties which can overcome these barriers. This review investigates and discusses the iron oxide nanoparticles, gold nanoparticles, platinum nanoparticles, silver nanoparticles, and silica-coated nanoparticles and how their unique properties after fabrication allow for their potential use in a wide range of bio-applications such as nano-based imaging, gene delivery, drug loading, and immunoassays. The different groups of nanoparticles and the advantages of surface functionalization and their applications are highlighted here. In recent years, surface-functionalized nanoparticles have become important materials for a broad range of bio-applications.

Enhancing Ocular Bioavailability of Ciprofloxacin Using Colloidal Lipid-Based Carrier for the Management of Post-Surgical Infection.

Conjunctivitis and endogenous bacterial endophthalmitis mostly occurred after ophthalmic surgery. Therefore, the present study aimed to maximize the ocular delivery of ciprofloxacin (CPX) using colloidal lipid-based carrier to control the post-surgical infection. In this study, CPX was formulated as ophthalmic liposomal drops. Two different phospholipids in different ratios were utilized, including phosphatidylcholine (PC) and dimyrestoyl phosphatidylcholine (DMPC). The physiochemical properties of the prepared ophthalmic liposomes were evaluated in terms of particle size, entrapment efficiency, polydispersity index, zeta potential, and cumulative CPX in-vitro release. In addition, the effect of sonication time on particle size and entrapment efficiency of CPX ophthalmic drops was also evaluated. The results revealed that most of the prepared formulations showed particle size in nanometer size range (460-1047 nm) and entrapment efficiency ranging from 36.4-44.7%. The antibacterial activity and minimum inhibitory concentration (MIC) were investigated. Ex vivo antimicrobial effect of promising formulations was carried out against the most common causes of endophthalmitis microorganisms. The pharmacokinetics of the prepared ophthalmic drops were tested in rabbit aqueous humor and compared with commercial CPX ophthalmic drops (Ciloxan®). Observed bacterial suppression was detected in rabbit's eyes conjunctivitis with an optimized formulation A3 compared with the commercial ophthalmic drops. CPX concentration in the aqueous humor was above MIC against tested bacterial strains. The in vivo data revealed that the tested CPX drops showed superiority over the commercial ones with respect to peak aqueous humor concentration, time to reach peak aqueous humor concentration, elimination rate constant, half-life, and relative bioavailability. Based on these results, it was concluded that the prepared ophthalmic formulations significantly enhanced CPX bioavailability compared with the commercial one.

Design, Characterization, and Antimicrobial Evaluation of Copper Nanoparticles Utilizing Tamarixinin a Ellagitannin from Galls of Tamarix aphylla.

The application of plant extracts or plant-derived compounds in the green synthesis of metal nanoparticles (NPs) was researched. Determining the exact metabolite implicated in the formation of NPs would necessitate comprehensive investigations. Copper nanoparticles (CuNPs) are gaining a lot of attention because of their unique properties and effectiveness against a wide range of bacteria and fungi, as well as their potential for usage in catalytic, optical, electrical, and microelectronics applications. In the course of this study, we aimed to formulate CuNPs utilizing pure tamarixinin A (TA) ellagitannin isolated from Tamarix aphylla galls. The main particle size of the formed CuNPs was 44 ± 1.7 nm with zeta potential equal to -23.7 mV, which emphasize the stability of the CuNPs. The X-ray diffraction spectroscopy showed a typical centered cubic crystalline structure phase of copper. Scanning electron microscopy images were found to be relatively spherical and homogeneous in shape. The antimicrobial properties of TA, as well as its mediated CuNPs, have been evaluated through well diffusion assays against four bacterial, Bacillus subtilis NCTC 10400, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853, and two fungal, Candida albicans and Aspergillus flavus, strains. The distinctive antimicrobial activities were noted against the fungal strains and the Gram-negative bacterial strains P. aeruginosa ATCC 27853, and E. coli ATCC 25922. In conclusion, CuNPs mediated by TA can be applied for combating a wide range of bacterial and fungal species especially C. albicans, Asp. flavus, and P. aeruginosa in a variety of fields.

Bacteria from Infectious Particles to Cell Based Anticancer Targeted Drug Delivery Systems.

Bacterial ghosts (BGs) are empty cell envelopes of nonliving evacuated bacterial cells. They are free from their cytoplasmic contents; however, they sustain their cellular 3D morphology and antigenic structures, counting on bioadhesive properties. Lately, they have been tested as an advanced drug delivery system (DDS) for different materials like DNA, peptides, or drugs, either single components or combinations. Different studies have revealed that, BG DDS were paid the greatest attention in recent years. The current review explores the impact of BGs on the field of drug delivery and drug targeting. BGs have a varied area of applications, including vaccine and tumor therapy. Moreover, the use of BGs, their synthesis, their uniqueness as a delivery system and application principles in cancer are discussed. Furthermore, the safety issues of BGs and stability aspects of using ghost bacteria as delivery systems are discussed. Future perspective efforts that must be followed for this important system to continue to grow are important and promising.

Formulation and in vitro and in vivo evaluation of surfactant-stabilized mucoadhesive nanogels for vaginal delivery of fluconazole.

Surfactant-stabilized mucoadhesive nanogels (NGs) for vaginal delivery of fluconazole (FLZ) were studied and evaluated in this work. FLZ-NG formulations were prepared using two different types of mucoadhesive polymers, Carbopol 934 (Ca934) and Pluronic F-127 (PF127). A rheology study revealed a non-Newtonian pseudoplastic flow behavior (shear thinning) in the prepared NGs. The viscosity of Ca934 NG (0.47 Pa s) was much lower compared to the PF127 NG (6.10 Pa s). The rheology study results correlated well with the in vitro FLZ release profile from the NG formulations. A pH study (pH = 3.90-4.90) revealed that the formulations were physiologically suitable for vaginal application, to avoid the irritation of the vaginal mucosa. Finally, in vitro and in vivo antimicrobial tests were performed. FLZ incorporated into the Ca934 gel had the strongest antimicrobial effect, with a mean inhibition zone of 24 ± 1.6 mm. Based on these results, it was concluded that the mucoadhesive NG incorporating FLZ resulted in a sustained release and enhanced antimicrobial effect, which would enhance and prolong the therapeutic effects of vaginally delivered FLZ.

Bioavailability assessment of hydroxymethylglutaryl coenzyme A reductase inhibitor utilizing pulsatile drug delivery system: a pilot study.

Chronotherapy or pulsatile drug delivery system could be achieved by increasing drug plasma concentration exactly at the time of disease incidence. Cholesterol synthesis shows a circadian rhythm being high at late night and early in the morning. Simvastatin (SIM) inhibits hydroxymethylglutaryl coenzyme A reductase, which is responsible for cholesterol synthesis. In this study, SIM lipid-based formulation filled in gelatin capsules and coated with aqueous Eudragit® S100 dispersion was prepared for chronotherapeutic treatment of hypercholesterolemia. The pharmacokinetic parameters of SIM capsules were studied in human volunteers after a single oral dose and compared with that of Zocor® tablets as a reference in a randomized cross-over study. Pharmacokinetic parameters such as AUC0-∞, Cmax, Tmax, t1/2 and elimination rate constant were determined from plasma concentration-time profile for both formulations. The tested formulation had the ability to delay drug absorption and provide higher drug concentrations from 3 up to 10 h after oral administration compared to that of commercial tablets. The data in this study revealed that the prepared formulation could be effective in chronotherapeutic treatment of hypercholesterolemia. Moreover, the tested formulation was found to enhance SIM bioavailability by 29% over the reference tablets.

Fast ultra-fine self-nanoemulsifying drug delivery system for improving in vitro gastric dissolution of poor water soluble drug.

Meloxicam (MLX) has poor water solubility which leads to slow absorption following oral administration; hence, immediate release tablet is unsuitable in the treatment of acute pain. The aim of this study was to prepare a novel fast ultra-fine self-nanoemulsifying drug delivery system (UF-SNEDDS) of MLX for oral administration to facilitate drug release process in the stomach as well as comparing its in vitro dissolution with commercial Mobic and Mobitil tablets. MLX solubility in oils, mixed glycerides and surfactants with different HLB values was investigated. Based on MLX solubility profiles, eight UF-SNEDDSs composed of MLX, Cremophor RH 40 as oily phase, Capmul MCM-C8 or Tween 80 as surfactant and PEG 400 as co-solvent were prepared and evaluated for their spontaneous formation of emulsion, droplet size, turbidity and in vitro dissolution. The prepared novel MLX formulations showed a significant very low droplets size (up to 25 nm), thermodynamically stable and spontaneously formed nanoemulsion. MLX UF-SNEDDS formulations showed significant high percentage of drug dissolution (up to 70%) in simulated gastric fluid, compared with Mobic and Mobitil. In conclusion, due to higher drug release from MLX UF-SNEDDS formulations they could enhance its absorption and hence its bioavailability.

Formulation and in vivo evaluation of diclofenac sodium sustained release matrix tablet: effect of compression force.

In the present study, Diclofenac Sodium (DS) matrix tablets were prepared by direct compression method under different compression forces (5, 10, 15 and 20 KN), using ethylcellulose as matrix forming material. The produced tablets were characterized on the foundation of satisfactory tablet properties such as hardness, friability, drug content, weight variations and in vitro drug release rate. Differential scanning calorimetry (DSC), Fourier Transform Infrared (FT-IR) spectroscopy and X-ray diffraction have been used to investigate any incompatibilities of the tablet's ingredients. Additionally, in vivo bioavailability has been investigated on beagle dogs. Data obtained revealed that, upon increasing compression force the in vitro drug release was sustained and the T(max) value was four hours (for formulations compressed at 15 and 20 kN) compared to the conventional voltarine(®) 50 tablets (T(max) value of 2 hours).

Evaluation of skin permeation and analgesic activity effects of carbopol lornoxicam topical gels containing penetration enhancer.

The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl ß-cyclodextrin (HP ß-CD), beta-cyclodextrin (ß-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 µg/cm(2)/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP ß-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP ß-CD and may be promising in enhancing permeation.