Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments.

Cell stiffness and T-box transcription factor 3 (TBX3) expression have been identified as biomarkers of melanoma metastasis in 2D environments. This study aimed to determine how mechanical and biochemical properties of melanoma cells change during cluster formation in 3D environments. Vertical growth phase (VGP) and metastatic (MET) melanoma cells were embedded in 3D collagen matrices of 2 and 4 mg/ml collagen concentrations, representing low and high matrix stiffness. Mitochondrial fluctuation, intracellular stiffness, and TBX3 expression were quantified before and during cluster formation. In isolated cells, mitochondrial fluctuation decreased and intracellular stiffness increased with increase in disease stage from VGP to MET and increased matrix stiffness. TBX3 was highly expressed in soft matrices but diminished in stiff matrices for VGP and MET cells. Cluster formation of VGP cells was excessive in soft matrices but limited in stiff matrices, whereas for MET cells it was limited in soft and stiff matrices. In soft matrices, VGP cells did not change the intracellular properties, whereas MET cells exhibited increased mitochondrial fluctuation and decreased TBX3 expression. In stiff matrices, mitochondrial fluctuation and TBX3 expression increased in VGP and MET, and intracellular stiffness increased in VGP but decreased in MET cells. The findings suggest that soft extracellular environments are more favourable for tumour growth, and high TBX3 levels mediate collective cell migration and tumour growth in the earlier VGP disease stage but play a lesser role in the later metastatic stage of melanoma.

A comprehensive review on transethosomes as a novel vesicular approach for drug delivery through transdermal route.

Drug delivery through transdermal route is one of the effective methods for the application of drugs. It overcomes many drawbacks which are encountered with the oral route. Moreover, many drugs are not able to pass through the stratum corneum, which is the main barrier for the transdermal drug delivery. Formation of ultra-deformable vesicles (UDVs) is a novel technique for the transdermal applications of the drugs. Transethosomes (TEs), ethosomes, and transferosomes are all part of the UDV. Because of the presence of increased concentrations of ethanol, phospholipids, and edge activators, TEs provide improved drug permeation through the stratum corneum. Because of the elasticity of TEs, drug penetration into the deeper layer of skin also increases. TEs can be prepared using a variety of techniques, including the cold method, hot method, thin film hydration method, and the ethanol injection method. It increases patient adherence and compliance because it is a non-invasive procedure of administering drugs. Characterization of the TEs includes pH determination, size and shape, zeta potential, particle size determination, transition temperature, drug content, vesicle stability, and skin permeation studies. These vesicular systems can be utilized to deliver a variety of medications transdermally, including analgesics, antibiotics, antivirals, and anticancer and arthritis medications. This review aims to describe vesicular approaches that had been used to overcome the barrier for the transdermal delivery of drug and also describes brief composition, method of preparation, characterization tests, mechanism of penetration of TEs, as well as highlighted various applications of TEs in medicine.

Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200mg/kg extract dose exhibited %age pain inhibition of 55.12% and reduced body temperature from 39.78±0.03°C to 37.22±0.02°C in hyperthermic rats. A decrease in blood glucose levels up to 57.88% was observed on the 21st day of the treatment with 500mg/kg ethanolic extract.

Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

A National Registry for People With All Stages of Kidney Disease: The National Kidney Foundation (NKF) Patient Network.

RATIONALE & OBJECTIVE: The National Kidney Foundation (NKF) launched the first national US kidney disease patient registry, the NKF Patient Network, that is open to patients throughout the continuum of chronic kidney disease (CKD). The Network provides individualized education and will facilitate patient-centered research, clinical care, and health policy decisions. Here, we present the overall design and the results of a feasibility study that was conducted July through December 2020. STUDY DESIGN: Longitudinal observational cohort study of patient-entered data with or without electronic health care record (EHR) linkage in collaboration with health systems. SETTING & PARTICIPANTS: People with CKD, age≥18 years, are invited through their provider, NKF communications, or national outreach campaign. People self-enroll and share their data through a secure portal that offers individualized education and support. The first health system partner is Geisinger. EXPOSURE: Any cause and stage of CKD, including dialysis and kidney transplant recipients. OUTCOME: Feasibility of the EHR data transfer, participants' characteristics, and their perspectives on usability and content. ANALYTICAL APPROACH: Data were collected and analyzed through the registry portal powered by the Pulse Infoframe healthie 2.0 platform. RESULTS: During the feasibility study, 80 participants completed their profile, and 42 completed a satisfaction survey. Mean age was 57.5 years, 51% were women, 83% were White, and 89% were non-Hispanic or Latino. Of the participants, 60% were not aware of their level of estimated glomerular filtration rate and 91% of their urinary albumin-creatinine ratio. LIMITATIONS: Challenges for the Network are lack of awareness of kidney disease for many with CKD, difficulty in recruiting vulnerable populations or those with low digital readiness, and loss to follow-up, all leading to selection bias. CONCLUSIONS: The Network is positioned to become a national and international platform for real-world data that can inform the development of patient-centered research, care, and treatments.

Photocatalytic Cross-Coupling of Tetrafluoropyridine Sulfides with Vinyl Halides for the Synthesis of ß,γ-Unsaturated Carbonyl Compounds.

ß,γ-Unsaturated carbonyl compounds serve as versatile building blocks in organic synthesis and medicinal chemistry. Herein we reported the synthesis of ß,γ-unsaturated carbonyl compounds from tetrafluoropyridine sulfides with vinyl halides. This cross-coupling reaction takes the advantage of photocatalysis, as well as zinc catalysis, which is preferred due to its less-toxic, earth abundant, and cost-effective nature.

Acute pancreatitis secondary to tamoxifen-associated hypertriglyceridemia: A clinical update.

INTRODUCTION: Drug-induced pancreatitis has been increasingly recognized, but it is frequently encountered as an inconspicuous etiology. The underlying mechanisms of injury vary with different drugs. Tamoxifen is a frequently used anticancer drug that acts by selective modulation of the estrogen receptor in patients with breast cancer. Tamoxifen-induced hypertriglyceridemia is a relatively rare etiological factor for acute pancreatitis. However, acute pancreatitis secondary to this adverse effect remains an exceedingly important clinicopathologic entity. CASE REPORT: We hereby delineate a rare case of acute pancreatitis secondary to hypertriglyceridemia in a patient who was on tamoxifen treatment for the past 3 years. Her serum lipase and triglyceride levels were markedly elevated at 14,285 IU/L and 20,344 mg/dL, respectively. The diagnosis was considered based on the findings of a standard diagnostic workup and exclusion of alternative causes of acute pancreatitis. MANAGEMENT AND OUTCOME: The patient was instituted prompt treatment with intravenous insulin infusion and gemfibrozil. The clinical outcome was favorable with no complications. Tamoxifen was permanently discontinued and was replaced with letrozole. DISCUSSION: This article illustrates that acute pancreatitis should be considered in the differential diagnoses of abdominal pain and elevated pancreatic enzymes in patients undergoing tamoxifen treatment. It also underscores the importance of pre- and post-tamoxifen lipid screening, especially in patients with a history of dyslipidemia and diabetes mellitus. It will facilitate an expedient detection of hypertriglyceridemia, potentially saving patients from associated morbidity and mortality.

Vesicular approach of cubosomes, its components, preparation techniques, evaluation and their appraisal for targeting cancer cells.

Cancer has been characterized by abnormal and uncontrolled proliferation of cells. Majority of drugs given through chemotherapy produce unwanted and adverse effects of chemotherapeutic agents to the other healthy cells and tissues of body. Various nanocarriers have now been considered for treatment of cancer. Among various nanocarriers, cubosomes are the nano sized dispersions that have drawn interest of researchers recently. Cubosomes are defined as dispersions of colloidal nature containing cubic crystalline liquid formations in aqueous medium in presence of suitable surfactant molecules. The unique capacity to encapsulate lipophilic, hydrophilic, and amphiphilic compounds inside their structure distinguishes them among others. Top- down method and hydrotrope method are most often employed methods for cubosomes preparation. Cubosomes can be characterized by Polarized light microscopy Photon correlation spectroscopy X-ray scattering (SAXS), Transmission electron microscopy and various stability studies. Cubic lipid nanoparticles have a very stable cubic structure that enables slower dissociation rate, increased retention and site-specific delivery of drugs. Cubosomes containing extracts of cornelian cherry for boosting anti-cancerous effects in cancer of colorectal cells by preventing against GIT destruction. When applied for skin cancer, cubosomes have shown to be having enhanced permeation of the drug. In liver cancer, increased bioavailability of drug was observed via cubosomes. This current review elaborates the advancement of cubosomes and their effective role in the treatment of cancer. This review aims to describe vesicular approach of cubosomes, its composition and method of preparation, characterization tests as well as elaborates various applications of cubosomes in cancer.

Solid lipid nanoparticles: a versatile approach for controlled release and targeted drug delivery.

Solid Lipid Nanoparticles (SLN), the first type of lipid-based solid carrier systems in the nanometer range, were introduced as a replacement for liposomes. SLN are aqueous colloidal dispersions with solid biodegradable lipids as their matrix. SLN is produced using processes like solvent diffusion method and high-pressure homogenization, among others. Major benefits include regulated release, increased bioavailability, preservation of peptides and chemically labile compounds like retinol against degradation, cost-effective excipients, better drug integration, and a broad range of applications. Solid lipid nanoparticles can be administered via different routes, such as oral, parenteral, pulmonary, etc. SLN can be prepared by using high shear mixing as well as low shear mixing. The next generation of solid lipids, nanostructured lipid carriers (NLC), can reduce some of the drawbacks of SLN, such as its restricted capacity for drug loading and drug expulsion during storage. NLC are controlled nanostructured lipid particles that enhance drug loading. This review covers a brief introduction of solid lipid nanoparticles, manufacturing techniques, benefits, limitations, and their characterization tests.

Patient Access in 14 High-Income Countries to New Antibacterials Approved by the US Food and Drug Administration, European Medicines Agency, Japanese Pharmaceuticals and Medical Devices Agency, or Health Canada, 2010-2020.

BACKGROUND: Inaccessibility of medicines in low- and middle-income countries is a frequent challenge. Yet it is typically assumed that high-income countries have complete access to the full arsenal of medicines. This study tests this assumption for new antibacterials, which are saved as a last resort in order to prevent the development of resistance, resulting in insufficient revenues to offset costs. Prior studies report only regulatory approval, missing the important lag that occurs between approval and commercial launch, although some antibiotics never launch in some countries. METHODS: We identified all antibacterials approved and launched in the G7 and 7 other high-income countries in Europe for the decade beginning 1 January 2010, using quantitative methods to explore associations. RESULTS: Eighteen new antibacterials were identified. The majority were accessible in only 3 countries (United States, United Kingdom, and Sweden), with the remaining 11 high-income countries having access to less than half of them. European marketing authorization did not lead to automatic European access, as 14 of the antibacterials were approved by the European Medicines Agency but many fewer were commercially launched. There was no significant difference in access between "innovative" and "noninnovative" antibacterials. Median annual sales in the first launched market (generally the United States) for these 18 antibiotics were low, $16.2M. CONCLUSIONS: Patient access to new antibacterials is limited in some high-income countries including Canada, Japan, France, Germany, Italy, and Spain. With low expected sales, companies may have decided to delay or forego commercialization due to expectations of insufficient profitability.

PharmaChk: a decade of research and development towards the first quantitative, field-based medicine quality screening instrument.

Biomedical and clinical scientists play a major role in translating observations into interventions - therapeutics, diagnostics, and medical devices including screening instruments - that improve the health of individuals and the public. This path from observation to intervention is often long and beset with obstacles, many unanticipated. We believe that sharing concrete, real-word examples of scientists in academia moving along this path will highlight some of the types of challenges one may face; here we focus on an intervention being developed by the Zaman lab at Boston University - PharmaChk, the first quantitative, field-based instrument for medicine quality screening. Specifically, this paper describes the first ten years of scientific and engineering work towards the development of this instrument. Launched from a need observed by medicine quality scientists, the development of PharmaChk has required the integration of multiple technologies enabled by knowledge and expertise across diverse fields of science and engineering, including chemistry, ultrasonics, fluid dynamics, optics, computer science, and automation. These efforts have been shaped and driven by the many challenges we have faced and the technical, commercial, and financial support that we have received from many collaborators. By sharing this example, we hope to inspire our colleagues to pursue their own paths to new healthcare solutions.

Identification and molecular characterization of cotton leaf curl Gezira betasatellite and two distinct begomoviruses infecting papaya trees in the Kingdom of Saudi Arabia.

Begomovirus is the largest genus in the family Geminiviridae and constitutes more than 445 virus species. Begomoviruses are characterized by single-stranded circular genomes with monopartite or bipartite components and transmitted by whitefly (Bemisia tabaci). Begomoviruses cause severe diseases in many economically important crops throughout the world. Typical symptoms of a begomovirus infection including severe leaf curling, vein thickening, vein darkening and reduced leaf size were observed in papaya plants in the Dammam district of the Eastern Province of Saudi Arabia during the growing season in 2022. A total of 10 samples were collected, and total genomic DNA was isolated from naturally infected papaya tree samples and subjected to PCR amplification using universal diagnostic primers for begomoviruses and associated satellites. Three PCR-amplified genomic components of begomoviruses and betasatellite namely P61Begomo (645 bp), P62Begomo (341 bp) and P62Beta (563 bp) were sent for Sanger DNA sequencing to Macrogen Inc. These partial viral genome sequences were submitted to Genbank database and accession numbers ON206051, ON206052 and ON206050 were assigned to P61Begomo, P62Begomo and P62Beta respectively. Phylogenetic analysis and pairwise nucleotide sequence identity studies identified P61Begomo was identified as Tomato yellow leaf curl virus, P62Begomo as DNA A component of a bipartite begomovirus Watermelon chlorotic stunt virus and P62Beta as begomovirus associated betasatellite; Cotton leaf curl Gezira betasatellite. To the best of our knowledge, this is the first report of a begomovirus complex infecting papaya (Carica papaya) in the Kingdom of Saudi Arabia.

A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

Inorganic arsenic (iAs) is a carcinogen, and exposure to iAs via food and water is a global public health problem. iAs-contaminated drinking water alone affects >100 million people worldwide, including ~50 million in Bangladesh. Once absorbed into the blood stream, most iAs is converted to mono-methylated (MMA) and then di-methylated (DMA) forms, facilitating excretion in urine. Arsenic metabolism efficiency varies among individuals, in part due to genetic variation near AS3MT (arsenite methyltransferase; 10q24.32). To identify additional arsenic metabolism loci, we measured protein-coding variants across the human exome for 1,660 Bangladeshi individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS). Among the 19,992 coding variants analyzed exome-wide, the minor allele (A) of rs61735836 (p.Val101Met) in exon 3 of FTCD (formiminotransferase cyclodeaminase) was associated with increased urinary iAs% (P = 8x10-13), increased MMA% (P = 2x10-16) and decreased DMA% (P = 6x10-23). Among 2,401 individuals with arsenic-induced skin lesions (an indicator of arsenic toxicity and cancer risk) and 2,472 controls, carrying the low-efficiency A allele (frequency = 7%) was associated with increased skin lesion risk (odds ratio = 1.35; P = 1x10-5). rs61735836 is in weak linkage disequilibrium with all nearby variants. The high-efficiency/major allele (G/Valine) is human-specific and eliminates a start codon at the first 5´-proximal Kozak sequence in FTCD, suggesting selection against an alternative translation start site. FTCD is critical for catabolism of histidine, a process that generates one-carbon units that can enter the one-carbon/folate cycle, which provides methyl groups for arsenic metabolism. In our study population, FTCD and AS3MT SNPs together explain ~10% of the variation in DMA% and support a causal effect of arsenic metabolism efficiency on arsenic toxicity (i.e., skin lesions). In summary, this work identifies a coding variant in FTCD associated with arsenic metabolism efficiency, providing new evidence supporting the established link between one-carbon/folate metabolism and arsenic toxicity.

Correction: A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

[This corrects the article DOI: 10.1371/journal.pgen.1007984.].

Effects of task-oriented training on dexterous movements of hands in post stroke patients.

Objective: The objective of the study was to determine the effect of task-oriented training on the dexterous movements of hands in Hemiplegic post-stroke patients.Methods: This study has been registered on site ClinicalTrial.gov with clinical trial number NCT05201196. The study was Randomized controlled trial, 18 patients were recruited that meet the inclusion criteria, randomly allocated to task-oriented training Group A (n = 9) and Conventional Therapy Group B (n = 9). Both exercise trainings were applied for 45 min/session, 5 times/week for 6 weeks. Fugl-Meyer Assessment Scale Motor, sensory and coordination portion, Wolf Motor Function Scale and Barthel Index were used as outcome measures, assessed patients at Baseline, after 3 weeks and 6 weeks after training. Data were analyzed by SPSS version 23.Results: The results suggested the mean Age was 60.78 ± 9.08 and 61.33 ± 6.78 for Group A and Group B, respectively. Average BMI was 23.66 ± 2.66 for Task-oriented group and 21.36 ± 2.46 for Conventional group. Fugl-Meyer scale shows significant P-value 0.03 post treatment compare to pre-treatment which was .283, Wolf Motor Function test and Barthel Index also showed significant P-values as 0.023 and 0.007, respectively, indicating that Task-oriented training shows more significant improvements than conventional group.Conclusion: Task-based training produced statistically significant as well as clinically meaningful enhancement in the dexterous hand movements of acute and subacute stroke patients than conventional therapy and ultimately improves the functional independence in their daily activities such as feeding, bathing and hygiene.

Fabrication of PEGylated Chitosan Nanoparticles Containing Tenofovir Alafenamide: Synthesis and Characterization.

Tenofovir alafenamide (TAF) is an antiretroviral (ARV) drug that is used for the management and prevention of human immunodeficiency virus (HIV). The clinical availability of ARV delivery systems that provide long-lasting protection against HIV transmission is lacking. There is a dire need to formulate nanocarrier systems that can help in revolutionizing the way to fight against HIV/AIDS. Here, we aimed to synthesize a polymer using chitosan and polyethylene glycol (PEG) by the PEGylation of chitosan at the hydroxyl group. After successful modification and confirmation by FTIR, XRD, and SEM, TAF-loaded PEGylated chitosan nanoparticles were prepared and analyzed for their particle size, zeta potential, morphology, crystallinity, chemical interactions, entrapment efficacy, drug loading, in vitro drug release, and release kinetic modeling. The fabricated nanoparticles were found to be in a nanosized range (219.6 nm), with ~90% entrapment efficacy, ~14% drug loading, and a spherical uniform distribution. The FTIR analysis confirmed the successful synthesis of PEGylated chitosan and nanoparticles. The in vitro analysis showed ~60% of the drug was released from the PEGylated polymeric reservoir system within 48 h at pH 7.4. The drug release kinetics were depicted by the Korsmeyer-Peppas release model with thermodynamically nonspontaneous drug release. Conclusively, PEGylated chitosan has the potential to deliver TAF from a nanocarrier system, and in the future, cytotoxicity and in vivo studies can be performed to further authenticate the synthesized polymer.

First report on molecular surveillance based on duplex detection of Anaplasma marginale and Theileria annulata in dairy cattle from Punjab, Pakistan.

Theileriosis and anaplasmosis are important tick-borne hemoparasites of bovines. The first surveillance study aimed to assess the suitability of duplex PCR for simultaneous detection of Theileria annulata and Anaplasma marginale field infections in Jhang and Rawalpindi districts of Punjab, Pakistan. Cattle blood samples (n = 480) were collected from selected union councils of all tehsils using a multistage sampling technique. The sampling unit consisted of asymptomatic cattle belonging to either age, sex, and breed. Epidemiological data related to host, area, management, and season were collected using a questionnaire. Based on duplex PCR, the overall prevalence of the two concurrent tick-borne pathogens was 19.79% (95/480). Chi-square analysis indicated that age, breed, tick infestation, history of tick-borne diseases, frequency of acaricidial application, and season were significantly associated with tick-borne pathogens. Phylogenetic analysis of A. marginale and T. annulata isolates based on msp1ß and cytochrome b genes, respectively, revealed that nucleotide sequences acquired from these two pathogens are novel, grouped separately from different countries. All our A. marginale isolates showed 88.2 to 80.5% similarity with isolates from Egypt, Israel, Mexico, and lesser homology with South African isolates. Similarly, the phylogenetic tree based on cytochrome b partial sequences of T. annulata revealed that our sequences are closer to those from India and Iran. Based on this first study on concomitant detection of tick-borne pathogens, it can be concluded that mixed infections are endemic in the study districts and mPCR is suitable for detecting concurrent field infections. Simultaneous infections should be considered while performing surveillance and chemotherapeutic trials for better prevention and control of tick-borne diseases.

Synthesis and characterization of self-assembling chitosan-based nanoparticles.

Chitosan (CHT) based biodegradable nanovectors were synthesized and modified with poly ethylene glycol 4000 (PEG-4000). CHT having medium molecular weight with 75% to 85% deacetylation was phthaloylated with phthalic anhydride, followed by PEGylation using PEG-4000. After confirmation of successful PEGylation by fourier transforminfra red spectroscopy (FTIR), the modified polymer was further processed to develop the nanocarrier using ionic gelation method by the addition of sodium tripolyphosphate (NaTPP). The prepared nanocarriers were subjected to physicochemical evaluation. The surface morphology of the particles was observed under scanning electron microscope (SEM), and particle size by dynamic light scattering (DLS) method, which was about 159-170nm in diameter. The zeta potential of the prepared nanovectors was +0.907mV which was due to cationic nature of nanovectors. The cell viability studies were also conducted to find the suitability of the carrier for in-vivo application, using liver cancerous cells (Hep G2). The findings have disclosed the concentration dependent activities of the particles, as viability of the cell was shown to be decreased with the increase in the concentration of the particles. Conclusively, the study was successful in determining the toxicity profile of these nanovectors as these were proved non-toxic at specific concentration.

Fast dissolving oral films: An approach to co-load and deliver the atorvastatin and ezetimibe for better therapeutic response.

Atherosclerotic patients suffering with acute coronary disease are lying at high risk. This life-threatening problem can be curtailed by using statins e.g., ezetimibe (EZT), atorvastatin calcium (ATC). In this study, co-loaded Fast Dissolving oral films (FDOFs), of ATC-EZT with HPMC E5 prepared by solvent evaporation method. Prepared FDOFs were evaluated for physicochemical, thermal and mechanical properties. In-vivo animal studies were performed on albino rats against diet induced hyperlipidemia. Prepared FDOFs have rapid DT; 27sec, TDT >2min and in-vitro drug release 97% in a min. In DSC, FTIR and XRD analysis, prepared films were chemically compatible and no chemical interaction of drugs and excipient was found. In kinetic modeling, it was observed their EZT exhibited lowest R2 value for zero order kinetic and best fit model was first order kinetic (n, 0.9823). The korsmeyer peppas model films (n, 0.016) indicate fickian type drug diffusion. The groups treated with marketed suspension of drug and FODPs were compared with normal group and high fats diet group. Study reviled that combination FDOPs of both ATC/EZT significantly reduce hyperlipemia as compared to high fat diet group. It can be concluded that ATC and EZT encapsulated in FODFs provide instant drug release and better therapeutic outcomes.

Optimization and fabrication of the nanosponge carriers of on dansetron using one-factor design.

The current studies were aimed to formulate ethyl cellulose (EC), beta-cyclodextrin (ß-CD facilitated EC based Ondansetron nanosponges (NS) using Response Surface Methodology (RSM) by employing One Factor Design. The NS were fabricated by Emulsion Solvent Diffusion method, followed by characterizations including, drug-polymer compatibility, entrapment efficiency, percentage yield, zeta size, zeta potential and in-vitro release of drug and Scanning Electron Microscopy (SEM) and X-Ray Diffractometry (XRD). The outcomes of Fourier Transformed Infra-Red Spectroscopy (FTIR) have confirmed the compatibility of the drug and excipients. It was found that NS have good entrapment efficiency along with their satisfactory percentage yield. Particle size analysis has confirmed the synthesis of nanosized NS (87.8nm to 108.2nm), having spongy surface, that was described by SEM results. Furthermore, the drug release studies have described a good sustained release of ondansetron for the period of 8 hours. The kinetic modeling has predicted that drug would follow the non fickian type of diffusion mechanism. The application of statistical approach was found helpful in designing and evaluating the NS, avoiding the laborious work, needs to be conducted while using hit and trial method.