Development of a Multifunctional Oral Dosage Form via Integration of Solid Dispersion Technology with a Black Seed Oil-Based Self-Nanoemulsifying Drug Delivery System.

Lansoprazole (LZP) is used to treat acid-related gastrointestinal disorders; however, its low aqueous solubility limits its oral absorption. Black seed oil (BSO) has gastroprotective effects, making it a promising addition to gastric treatment regimens. The present study aims to develop a stable multifunctional formulation integrating solid dispersion (SD) technology with a bioactive self-nanoemulsifying drug delivery system (SNEDDS) based on BSO to synergistically enhance LZP delivery and therapeutic effects. The LZP-loaded SNEDDS was prepared using BSO, Transcutol P, and Kolliphor EL. SDs were produced by microwave irradiation and lyophilization using different polymers. The formulations were characterized by particle apparent hydrodynamic radius analysis, zeta potential, SEM, DSC, PXRD, and in vitro dissolution testing. Their chemical and physical stability under accelerated conditions was also examined. Physicochemical characterization revealed that the dispersed systems were in the nanosize range (<500 nm). DSC and PXRD studies revealed that lyophilization more potently disrupted LZP crystallinity versus microwave heating. The SNEDDS effectively solubilized LZP but degraded completely within 1 day. Lyophilized SDs with Pluronic F-127 demonstrated the highest LZP dissolution efficiency (3.5-fold vs. drug) and maintained chemical stability (>97%) for 1 month. SDs combined with the SNEDDS had variable effects suggesting that the synergistic benefits were dependent on the formulation and preparation method. Lyophilized LZP-Pluronic F127 SD enabled effective and stable LZP delivery alongside the bioactive effects of the BSO-based SNEDDS. This multifunctional system is a promising candidate with the potential for optimized gastrointestinal delivery of LZP and bioactive components.

Gene-editing technology, from macromolecule therapeutics to organ transplantation: Applications, limitations, and prospective uses.

Gene editing technologies (GETs) could induce gene knockdown or gene knockout for biomedical applications. The clinical success of gene silence by RNAi therapies pays attention to other GETs as therapeutic approaches. This review aims to highlight GETs, categories, mechanisms, challenges, current use, and prospective applications. The different academic search engines, electronic databases, and bibliographies of selected articles were used in the preparation of this review with a focus on the fundamental considerations. The present results revealed that, among GETs, CRISPR/Cas9 has higher editing efficiency and targeting specificity compared to other GETs to insert, delete, modify, or replace the gene at a specific location in the host genome. Therefore, CRISPR/Cas9 is talented in the production of molecular, tissue, cell, and organ therapies. Consequently, GETs could be used in the discovery of innovative therapeutics for genetic diseases, pandemics, cancer, hopeless diseases, and organ failure. Specifically, GETs have been used to produce gene-modified animals to spare human organ failure. Genetically modified pigs are used in clinical trials as a source of heart, liver, kidneys, and lungs for xenotransplantation (XT) in humans. Viral, non-viral, and hybrid vectors have been utilized for the delivery of GETs with some limitations. Therefore, extracellular vesicles (EVs) are proposed as intelligent and future cargoes for GETs delivery in clinical applications. This study concluded that GETs are promising for the production of molecular, cellular, and organ therapies. The use of GETs as XT is still in the early stage as well and they have ethical and biosafety issues.

Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles.

Lung cancer is a formidable challenge in clinical practice owing to its metastatic nature and resistance to conventional treatments. The codelivery of anticancer agents offers a potential solution to overcome resistance and minimize systemic toxicity. The encapsulation of these agents within nanostructured lipid carriers (NLCs) provides a promising strategy to enhance lymphatic delivery and reduce the risk of relapse. This study aimed to develop an NLC formulation loaded with Gefitinib and Azacitidine (GEF-AZT-NLC) for the treatment of metastatic-resistant lung cancer. The physicochemical properties of the formulations were characterized, and in vitro drug release was evaluated using the dialysis bag method. The cytotoxic activity of the GEF-AZT-NLC formulations was assessed on a lung cancer cell line, and hemocompatibility was evaluated using suspended red blood cells. The prepared formulations exhibited nanoscale size (235-272 nm) and negative zeta potential values (-15 to -31 mV). In vitro study revealed that the GEF-AZT-NLC formulation retained more than 20% and 60% of GEF and AZT, respectively, at the end of the experiment. Hemocompatibility study demonstrated the safety of the formulation for therapeutic use, while cytotoxicity studies suggested that the encapsulation of both anticancer agents within NLCs could be advantageous in treating resistant cancer cells. In conclusion, the GEF-AZT-NLC formulation developed in this study holds promise as a potential therapeutic tool for treating metastatic-resistant lung cancer.

Coding Therapeutic Nucleic Acids from Recombinant Proteins to Next-Generation Vaccines: Current Uses, Limitations, and Future Horizons.

This study aims to highlight the potential use of cTNAs in therapeutic applications. The COVID-19 pandemic has led to significant use of coding therapeutic nucleic acids (cTNAs) in terms of DNA and mRNA in the development of vaccines. The use of cTNAs resulted in a paradigm shift in the therapeutic field. However, the injection of DNA or mRNA into the human body transforms cells into biological factories to produce the necessary proteins. Despite the success of cTNAs in the production of corona vaccines, they have several limitations such as instability, inability to cross biomembranes, immunogenicity, and the possibility of integration into the human genome. The chemical modification and utilization of smart drug delivery cargoes resolve cTNAs therapeutic problems. The success of cTNAs in corona vaccine production provides perspective for the eradication of influenza viruses, Zika virus, HIV, respiratory syncytial virus, Ebola virus, malaria, and future pandemics by quick vaccine design. Moreover, the progress cTNAs technology is promising for the development of therapy for genetic disease, cancer therapy, and currently incurable diseases.

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.

Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons.

Lymphatic drug targeting is an effective approach for targeting immunomodulators, and chemotherapeutic drugs at a specific organ or cellular location. The cellular, paracellular, and dendritic cell trafficking machinery are involved in the lymphatic transport of therapeutic agents. The engineering of triggered and hybrid lymphatic drug delivery systems (LDDS) is a promising strategy to fight cancer metastasis and microbial pandemics. Hybrid lymphatic drug delivery systems can be tailored and developed by grafting the conventional LDDS with biological agents. Thus, hybrid LDDS could collect the benefits of conventional and biological delivery systems. Moreover, the fabrication of triggered LDDS increases drug accumulation in the lymphatic system in the response to an internal stimulus such as pH, and redox status or external such as magnetic field, temperature, and light. Stimuli-responsive LDD systems prevent premature release of payload and mediate selective drug biodistribution. This improves therapeutic impact and reduces the systemic side effect of anticancer, immunomodulatory, and antimicrobial therapeutics. This review highlights the challenges and future horizons of nanoscaled-triggered LDDS and their influence on the lymphatic trafficking of therapeutic molecules.

Optimization of Gefitinib-Loaded Nanostructured Lipid Carrier as a Biomedical Tool in the Treatment of Metastatic Lung Cancer.

Gefitinib (GEF) is utilized in clinical settings for the treatment of metastatic lung cancer. However, premature drug release from nanoparticles in vivo increases the exposure of systemic organs to GEF. Herein, nanostructured lipid carriers (NLC) were utilized not only to avoid premature drug release but also due to their inherent lymphatic tropism. Therefore, the present study aimed to develop a GEF-NLC as a lymphatic drug delivery system with low drug release. Design of experiments was utilized to develop a stable GEF-NLC as a lymphatic drug delivery system for the treatment of metastatic lung cancer. The in vitro drug release of GEF from the prepared GEF-NLC formulations was studied to select the optimum formulation. MTT assay was utilized to study the cytotoxic activity of GEF-NLC compared to free GEF. The optimized GEF-NLC formulation showed favorable physicochemical properties: <300 nm PS, <0.2 PDI, <−20 ZP values with >90% entrapment efficiency. Interestingly, the prepared formulation was able to retain GEF with only ≈57% drug release within 24 h. Furthermore, GEF-NLC reduced the sudden exposure of cultured cells to GEF and produced the required cytotoxic effect after 48 and 72 h incubation time. Consequently, optimized formulation offers a promising approach to improve GEF's therapeutic outcomes with reduced systemic toxicity in treating metastatic lung cancer.

TPGS decorated NLC shift gefitinib from portal absorption into lymphatic delivery: Intracellular trafficking, biodistribution and bioavailability studies.

Lymphatic drug delivery (LDD) is an attractive option for the prevention and treatment of cancer metastasis. This study aims to develop TPGS decorated nanostructure lipid carrier gefitinib loaded (TPGS-NLC-GEF). Biocompatibility and cytotoxicity were studied using erythrocytes and A549 cell lines. Furthermore, cellular uptake of the prepared TPGS-NLC was studied using 5-carboxyfluorescein (5-CF). Pharmacokinetic, biodistribution, and chylomicron-block flow studies were performed using male Wister Albino rats to investigate the influence of TPGS-NLC on plasma concentration-time profile, organ deposition, and LDD of GEF. The present results indicated that the prepared TPGS-NLC and TPGS-NLC-GEF formulation had a particle size range of 268 and 288 nm with a negative zeta-potential value of - 29.3 and - 26.5 mV, respectively. The in-vitro release showed burst drug release followed by sustained release. In addition, the biosafety in the term of the hemocompatibility study showed that the prepared formulation was safe at the therapeutic level. Additionally, an in-vitro cytotoxicity study showed that the TPGS-NLC was able to enhance the activity of GEF against the A549 cell line. The cellular uptake study showed the ability of TPGS-NLC to enhance 5-CF internalization by 12.6-fold compared to the 5-CF solution. Furthermore, the in-vivo study showed that TPGS-NLC was able to enhance GEF bioavailability (1.5-fold) through lymphatic system which was confirmed via the indirect chylomicron-block flow method. The tissue distribution study showed the ability of lipid nanoparticles to enhance lung drug deposition by 5.8-fold compared to a GEF suspension. This study concluded that GEF-NLC-GEF is an encouraging approach for the treatment of metastatic lung cancer through lymphatic delivery, enhanced bioavailability, and reduced systemic toxicity.

Combined Ramipril and Black Seed Oil Dosage Forms Using Bioactive Self-Nanoemulsifying Drug Delivery Systems (BIO-SNEDDSs).

Purpose: Ramipril (RMP)­an angiotensin-converting enzyme (ACE) inhibitor­and thymoquinone (THQ) suffer from poor oral bioavailability. Developing a combined liquid SNEDDS that comprises RMP and black seed oil (as a natural source of THQ) could lead to several formulations and therapeutic benefits. Methods: The present study involved comprehensive optimization of RMP/THQ liquid SNEDDS using self-emulsification assessment, equilibrium solubility studies, droplet size analysis, and experimentally designed phase diagrams. In addition, the optimized RMP/THQ SNEDDS was evaluated against pure RMP, pure THQ, and the combined pure RMP + RMP-free SNEDDS (capsule-in-capsule) dosage form via in vitro dissolution studies. Results: The phase diagram study revealed that black seed oil (BSO) showed enhanced self-emulsification efficiency with the cosolvent (Transcutol P) and hydrogenated castor oil. The phase diagram studies also revealed that the optimized formulation BSO/TCP/HCO-30 (32.25/27.75/40 % w/w) showed high apparent solubility of RMP (25.5 mg/g), good THQ content (2.7 mg/g), and nanometric (51 nm) droplet size. The in-vitro dissolution studies revealed that the optimized drug-loaded SNEDDS showed good release of RMP and THQ (up to 86% and 89%, respectively). Similarly, the isolation between RMP and SNEDDS (pure RMP + RMP-free SNEDDS) using capsule-in-capsule technology showed >84% RMP release and >82% THQ release. Conclusions: The combined pure RMP + RMP-free SNEDDS (containing black seed oil) could be a potential dosage form combining the solubilization benefits of SNEDDSs, enhancing the release of RMP/THQ along with enhancing RMP stability through its isolation from lipid-based excipients during storage.

PEGylated SLN as a Promising Approach for Lymphatic Delivery of Gefitinib to Lung Cancer.

Purpose: The present study aimed to develop gefitinib-loaded solid lipid nanoparticles (GEF-SLN), and GEF-loaded PEGylated SLN (GEF-P-SLN) for targeting metastatic lung cancer through the lymphatic system. Methods: The prepared SLNs were characterized in terms of physicochemical properties, entrapment efficiency, and in-vitro release. Furthermore, ex-vivo permeability was investigated using the rabbit intestine. Cytotoxicity and apoptotic effects were studied against A549 cell lines as a model for lung cancer. Results: The present results revealed that the particle size and polydispersity index of the prepared formulations range from 114 to 310 nm and 0.066 to 0.350, respectively, with negative zeta-potential (-14 to -27.6). Additionally, SLN and P-SLN showed remarkable entrapment efficiency above 89% and exhibited sustained-release profiles. The permeability study showed that GEF-SLN and GEF-P-SLN enhanced the permeability of GEF by 1.71 and 2.64-fold, respectively, compared with GEF suspension. Cytotoxicity showed that IC50 of pure GEF was 3.5 µg/mL, which decreased to 1.95 and 1.8 µg/mL for GEF-SLN and GEF-P-SLN, respectively. Finally, the apoptotic study revealed that GEF-P-SLN decreased the number of living cells from 49.47 to 3.43 when compared with pure GEF. Conclusion: These results concluded that GEF-P-SLN is a promising approach to improving the therapeutic outcomes of GEF in the treatment of metastatic lung cancer.

Engineered Nanoscale Lipid-Based Formulation as Potential Enhancer of Gefitinib Lymphatic Delivery: Cytotoxicity and Apoptotic Studies Against the A549 Cell Line.

The present study aimed to engineer a nanoscale lipid-based lymphatic drug delivery system with D-α-Tocopherol polyethylene glycol 1000 succinate to combat the lymphatic metastasis of lung cancer. The nanoscale lipid-based systems including GEF-SLN, GEF-NLC, and GEF-LE were prepared and pharmaceutically characterized. In addition, the most stable formulation (GEF-NLC) was subjected to an in vitro release study. Afterward, the optimized GEF-NLC was engineered with TPGS (GEF-TPGS-NLC) and subjected to in vitro cytotoxicity, and apoptotic studies using the A549 cells line as a surrogate model for lung cancer. The present results revealed that particle size and polydispersity index of freshly prepared formulations were ranging from 198 to 280 nm and 0.106 to 0.240, respectively, with negative zeta potential ranging from - 14 to - 27.6.mV. An in vitro release study showed that sustained drug release was attained from GEF-NLC containing a high concentration of lipid. In addition, GEF-NLC and GEF-TPGS-NLC showed remarkable entrapment efficiency above 89% and exhibited sustained release profiles. Cytotoxicity showed that IC50 of pure GEF was 11.15 µg/ml which decreased to 7.05 µg/ml for GEF-TPGS-NLC. The apoptotic study revealed that GEF-TPGS-NLC significantly decreased the number of living cells from 67 to 58% when compared with pure GEF. The present results revealed that the nanoscale and lipid composition of the fabricated SLN, NLC, and LE could mediate the lymphatic uptake of GEF to combat the lymphatic tumor metastasis. Particularly, GEF-TPGS-NLC is a promising LDDS to increase the therapeutic outcomes of GEF during the treatment of metastatic lung cancer.

Development and Evaluation of Interactive Flipped e-Learning (iFEEL) for Pharmacy Students during the COVID-19 Pandemic.

Background: Distance learning has come to the forefront of educational delivery throughout the world due to the COVID-19 pandemic. Presently, there is a paucity of studies that have utilized interactive e-lectures as a model for remote flipped learning. Objectives: To compare educational outcomes for the remote interactive flipped e-learning (iFEEL) activity versus paper-based in-class group learning (PICkLE). Methods: During the spring 2021 semester, tutorials in pharmaceutical quality control and good manufacturing practice were remotely delivered to students by two different approaches: PICkLE and iFEEL. In the latter activity, interactive e-lectures were software-designed and included several audiovisual enhanced illustrations to encourage students to interact with the lecture material prior to attending the virtual class. The class time was reserved for in-class quizzes and discussion. Mean exam scores were compared and voluntary questionnaires were distributed among the participating students as well as healthcare faculty members in 29 Saudi universities. Data from the remotely-delivered course was compared with data from previous course offerings (2018−2020) that used the live PICkLE method. Results: The mean score of post-lecture tests significantly (p < 0.05) increased compared to pre-lecture tests in remote PICkLE and iFEEL, respectively. iFEEL activity showed higher mean post-tests score (95.2%) compared to live PICkLE (90.2%, p = 0.08) and remote PICkLE (93.5%, p = 0.658). Mean comprehensive exam scores increased from 83.8% for remote PICkLE to 89.2% for iFEEL (p = 0.449). On average, 92% of students and 85% of faculty members reported positive feedback on the five quality attributes of the e-lecture. Over 75% of students preferred the iFEEL over PICkLE activity for future course offerings and 84% of faculty members recommend the integration of interactive e-lectures in their future courses. Conclusion: iFEEL represents a novel model of remote flipped learning and shows promising potential to be incorporated into live blended-learning classroom activities.

Zingerone (4-(four-hydroxy-3-methylphenyl) butane-two-1) modulates adjuvant-induced rheumatoid arthritis by regulating inflammatory cytokines and antioxidants.

OBJECTIVE: Ginger (Zingiber officinale Roscoe) is considered to be one of the most commonly consumed dietary condiments of the world. The present study was designed to explicate the protective role of zingerone; an active ingredient of ginger in complete Freund's adjuvant (FCA)-immunized arthritic rats. METHODS: 24 Wistar rats were divided into 4 groups with 6 rats each. Group I as control followed by group II, III and IV were treated with single intradermal injection of FCA (0.1 ml = 100 µg) to induce rheumatoid arthritis. Group III and IV were also administered with zingerone orally at 25 mg/kg b.w for 3 weeks at two different time points. RESULTS: Adjuvant-treated rats exhibited a significant increase in lipid peroxidation and a reduction in the enzymatic antioxidants such as SOD, catalase and GPx, in the liver and joint tissues. Moreover, FCA inoculation resulted in the increase in levels of NF-κB, TGF-ß, TNF-α, IL-1ß, IL-6 and Hs-CRP and a decrease in IL-10 levels. Zingerone significantly reduced the levels of NF-κB, TGF-ß, TNF-α, IL-1ß, IL-6 and Hs-CRP and markedly increased IL-10 levels. Levels of antioxidant enzymes were also restored by zingerone treatment. DISCUSSION: Oral administration of zingerone ameliorated inflammatory outburst and decreased oxidative stress, suggesting its role in the prevention of rheumatoid arthritis. Further mechanistic insights are necessary to study the exact mechanism involved.

Bacteriosomes as a Promising Tool in Biomedical Applications: Immunotherapy and Drug Delivery.

Bacteriosomes are a member of cell-derived vesicles that are proposed as promising tools in diagnosis, therapy, and drug delivery. These vesicles could be derived from a virus, bacterial cells, and animal cells. Biotechnology techniques were used in bioengineering of cell-derived vesicles in vitro, and in vivo. Bacterial vesicles such as bacterial cells, bacterial ghost, or bacteriosomes are vesicular structures derived from bacteria produced by manipulation of bacterial cells by chemical agents or gene-mediated lysis. Subsequently, bacterial vesicles (bacteriosomes) are non-living, non-denatured bacterial cell envelopes free of the cytoplasm and genetic materials. Gram-negative and Gram-positive bacteria are exploited in the production of bacteriosomes. Bacteriosomes have instinct organs, tissues, cells, as well as subcellular tropism. Moreover, bacteriosomes might be used as immunotherapy and/or drug delivery shuttles. They could act as cargoes for the delivery of small drugs, large therapeutics, and nanoparticles to the specific location. Furthermore, bacteriosomes have nature endosomal escaping ability, hence they could traffic different bio-membranes by endocytosis mechanisms. Therefore, bacterial-derived vesicles could be used in therapy and development of an innovative drug delivery systems. Consequently, utilizing bacteriosomes as drug cargoes enhances the delivery and efficacy of administered therapeutic agents. This review highlighted bacteriosomes in terms of source, engineering, characterization, applications, and limitations.

Bioactive Self-Nanoemulsifying Drug Delivery Systems (Bio-SNEDDS) for Combined Oral Delivery of Curcumin and Piperine.

Background: Bioactive oils of natural origin have gained huge interests from health care professionals and patients. Objective: To design a bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS) comprising curcumin (CUR) and piperine (PP) by incorporating bioactive natural oils in the formulation. Methods: The self-emulsifying properties of apricot, avocado, black seed and Zanthoxylum rhetsa seed oils were screened within various SNEDDS formulations. Each liquid SNEDDS formulation was loaded with both CUR and PP. The optimal liquid SNEDDS were solidified using Aeroperl® and Neusilin® at 1:1 w/w ratio. Liquid and solid SNEDDS were characterized by droplet size analysis, equilibrium solubility, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. In-vitro dissolution studies were performed to evaluate the efficiency of CUR and PP release from solid Bio-SNEDDS. Results: The liquid SNEDDS comprised of black seed oil exhibited excellent self-emulsification performance, low droplet size along with transparent appearance. The inclusion of the cosolvent Transcutol P improved the solubilization capacity of both CUR and PP. The liquid SNEDDS were efficiently solidified using the two adsorbents and presented the drugs within amorphous state. In particular, SNEDDS comprised of black seed oil/Imwitor988/Transcutol P/Cremophor RH40 (20/20/10/50) and when solidified with Neusilin showed enhanced CUR and PP release (up to 60% and 77%, respectively). In addition, this formulation efficiently delivers the highly bioactive black seed oil to the patient. Conclusions: The optimized Bio-SNEDDS comprising black seed oil showed outstanding self-emulsification characteristics along with enhanced CUR/PP dissolution upon solidification.

Engineering of Exosomes: Steps Towards Green Production of Drug Delivery System.

Targeting of therapeutic agents to their specific site of action not only increases the treatment efficacy, but also reduces systemic toxicity. Therefore, various drug delivery systems (DDSs) have been developed to achieve this target. However, most of those DDSs have several issues regarding biocompatibility and environmental hazard. In contrast to the synthetic DDSs, exosome-based natural carriers are biocompatible, biodegradable and safe for the environment. Since exosomes play a role in intercellular communication, they have been widely utilized as carriers for different therapeutic agents. This article was aimed to provide an overview of exosomes as an environment-friendly DDS in terms of engineering, isolation, characterization, application and limitation.

Evaluation of the bioavailability of hydrocortisone when prepared as solid dispersion.

This study was conducted to formulate, characterize, and investigate the bioavailability of hydrocortisone (HCT) when prepared as solid dispersions. HCT was mixed in an organic solvent with polyethylene glycol 4000 (PEG 4000) and Kolliphor® P 407. Spray drying technique was employed to form a solid dispersion formulation at a specific ratio. Physical and chemical characterization of the formed particles were achieved using differential scanning calorimetry, scanning electron microscopy, Fourier transform infrared spectroscopy, and powder X-ray diffractometry. Furthermore, comparative in vitro and in vivo studies were conducted between the formulated particles against neat HCT. The formulated solid dispersion showed elongated particles with leaf-like structure. Formation of new chemical bonds in the formed particle was suggested due to the change in the vibrational wave numbers and the significant improvement in the bioavailability of the dispersed particles proved the importance of this technique.

Novel in-situ gel for intravesical administration of ketorolac.

The urinary bladder stores urine until the time of urination. Systemic administration of drugs to treat bladder diseases faces several limitations. Therefore, intravesical drug delivery is a promising alternative route of administration. An in-situ gel is used to form a gel inside the bladder cavity and ensure continuous release of the drug even after urination. The objective of the present study was to optimize an in-situ gel formulation of poloxamer and chitosan for intravesical delivery of ketorolac tromethamine. The gelling temperature of the prepared combinations ranged from 20.67 to 25.8 °C. In-vitro release of KT was sustained for up to 7 h using a poloxamer concentration ranging from 17% to 19% and a chitosan concentration ranging from 1% to 2%. Design-Expert® 10 was used to select the optimized formulation (poloxamer/chitosan 17/1.589% w/w) which significantly (p < 0.05) extended the drug release more than each polymer alone. An ex-vivo study showed the ability of the optimized formulation to sustain drug release after emptying two times to mimic urination. Furthermore, the formed gel adhered to the bladder tissue throughout the time period of the experiment. Intravesical administration of the optimized formulation to rabbits via catheter showed no obstruction of urine flow and continuous release of the drug for 12 h.

Novel Thiourea Derivatives Bearing Sulfonamide Moiety as Anticancer Agents Through COX-2 Inhibition.

BACKGROUND: Thiourea derivatives bearing sulfonamide moiety are well known for their anticancer activity. OBJECTIVE: The anticancer activity of the target compounds was studied, via inhibition of COX-2 enzyme. METHOD: A series of novel thioureas 5a-n, 8, quinazoline 6, benzo[g]quinazoline 7 and benzo[1,3] dioxole 10, bearing a sulfonamide moiety was synthesized from the starting compound N-(2,6-dimethoxypyrimidin-4-yl)-4- isothiocyanatobenzenesulfonamide 2. The target compounds were screened against HepG2, MCF-7, Caco-2, HCT-116, PC-3 cancer cell lines and VERO-B normal cell line. RESULTS: Out of all the tested compounds, compound 5c showed a broad selective cytotoxicity against HepG2, MCF-7, Caco-2 and PC-3 cancer cells. Moreover, a sensitization assay was performed on Caco-2 cells, and compound 5c proved to act as a chemosensitizer for cisplatin on colon cancer (Caco-2) cells. The target compounds were further screened in vitro for their anti COX1/COX2 activity and investigated in vivo as antiinflammatory agents against carrageenan-induced rat paw oedema model. CONCLUSION: Compound 5g showed the most selective inhibitory activity against COX-2. While, compounds 5a, 6, 5m, 5n, 5g and 5i revealed significant anti-inflammatory effect as presented in carrageenan-induced oedema assay. Molecular docking of the tested compounds disclosed important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme.