Optimizing lornoxicam-loaded poly(lactic-co-glycolic acid) and (polyethylene glycol) nanoparticles for transdermal delivery: ex vivo/in vivo inflammation evaluation.

Aim: This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to mitigate gastrointestinal (GIT) side effects and enhance therapeutic efficacy. Materials & methods: Synthesized nanoparticles were subjected to in vitro characterization, ex vivo permeation studies, and acute oral toxicity analysis post-incorporation into the gel using a S/O/W double emulsion solvent. Results & conclusion: The nanoparticles displayed a smooth, spherical morphology (170-321 nm) with increased entrapment efficiency (96.2%). LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX.

[Box: see text].

pH-sensitive docetaxel-loaded chitosan/thiolated hyaluronic acid polymeric nanoparticles for colorectal cancer.

Aim: This study aimed to develop and evaluate pH-sensitive docetaxel-loaded thiolated hyaluronic acid (HA-SH) nanoparticles (NPs) for targeted treatment of colon cancer. Materials & methods: HA-SH, synthesized via oxidation and subsequent covalent linkage to cysteamine, served as the precursor for developing HA-SH NPs through polyelectrolyte complexation involving chitosan and thiol-bearing HA. Results & conclusion: HA-SH NPs displayed favorable characteristics, with small particle sizes (184-270 nm), positive zeta potential (15.4-18.6 mV) and high entrapment efficiency (91.66-95.02%). In vitro, NPs demonstrated potent mucoadhesion and enhanced cytotoxicity compared with free docetaxel. In vivo assessments confirmed safety and biocompatibility, suggesting HA-SH NPs as promising pH-sensitive drug carriers with enhanced antitumor activity for colorectal cancer treatments.

Fabrication of solid lipid nanoparticles-based patches of paroxetine and their ex-vivo permeation behaviour.

Paroxetine is not suitable for oral administration due to its extensive first-pass metabolism, thus resulting in less bioavailability. This study aimed to prepare novel paroxetine-loaded solid lipid nanoparticles (SLNs) based sustained-release transdermal patches to overcome these problems by enhancing drug absorption and bioavailability. Nine formulations of paroxetine SLNs were prepared by the hot melt-homogenization method using different concentrations of glycerol monostearate (Kolliwax) and Tween 80. Then these prepared SLNs were incorporated in a matrix type transdermal patch having a matrix of ethyl cellulose and polyvinyl pyrrolidone in 3:2 with polyvinyl alcohol. The SLNs showed a particle size range of 113-230 nm and an entrapment efficiency of 85.14%. The SLNs showed sustained paroxetine release (77.86-95.63% release) up to 48 h. FTIR studies showed no interaction between drug and formulation components. Paroxetine is evenly distributed in an amorphous form in SLNs, as demonstrated by DSC as well as PXRD analysis. SLNs formulated patches showed higher drug permeation through the skin than drug-based transdermal patches., Draize patch test revealed no sign of erythema after applying paroxetine-loaded SLN patches (score 0) as observed with the marketed product. The developed SLNs based transdermal patches showed increased permeability and sustained release behaviour.

An Inventory of Anthelmintic Plants across the Globe.

A wide range of novelties and significant developments in the field of veterinary science to treat helminth parasites by using natural plant products have been assessed in recent years. To the best of our knowledge, to date, there has not been such a comprehensive review of 19 years of articles on the anthelmintic potential of plants against various types of helminths in different parts of the world. Therefore, the present study reviews the available information on a large number of medicinal plants and their pharmacological effects, which may facilitate the development of an effective management strategy against helminth parasites. An electronic search in four major databases (PubMed, Scopus, Web of Science, and Google Scholar) was performed for articles published between January 2003 and April 2022. Information about plant species, local name, family, distribution, plant tissue used, and target parasite species was tabulated. All relevant studies meeting the inclusion criteria were assessed, and 118 research articles were included. In total, 259 plant species were reviewed as a potential source of anthelmintic drugs. These plants can be used as a source of natural drugs to treat helminth infections in animals, and their use would potentially reduce economic losses and improve livestock production.

Natural polysaccharide-based biodegradable polymeric platforms for transdermal drug delivery system: a critical analysis.

Natural biodegradable polymers generally include polysaccharides (starch, alginate, chitin/chitosan, hyaluronic acid derivatives, etc.) and proteins (collagen, gelatin, fibrin, etc.). In transdermal drug delivery systems (TDDS), these polymers play a vital role in controlling the device's drug release. It is possible that natural polymers can be used for TDDS to attain predetermined drug delivery rates due to their physicochemical properties. These polymers can be employed to market products and scale production because they are readily available and inexpensive. As a result of these polymers, new pharmaceutical delivery systems can be developed that is both regulated and targeted. The focus of this article is the application of a biodegradable polymeric platform based on natural polymers for TDDS. Due to their biocompatibility and biodegradability, natural biodegradable polymers are frequently used in biomedical applications. Additionally, these natural biodegradable polymers are being studied for their characteristics and behaviors.

Development of ß-cyclodextrin/polyvinypyrrolidone-co-poly (2-acrylamide-2-methylpropane sulphonic acid) hybrid nanogels as nano-drug delivery carriers to enhance the solubility of Rosuvastatin: An in vitro and in vivo evaluation.

The present study is aimed at enhancing the solubility of rosuvastatin (RST) by designing betacyclodextrin/polyvinypyrrolidone-co-poly (2-acrylamide-2-methylpropane sulphonic acid) crosslinked hydrophilic nanogels in the presence of crosslinker methylene bisacrylamide through free-radical polymerization method. Various formulations were fabricated by blending different amounts of betacyclodextrin, polyvinylpyrrolidone, 2-acrylamide-2-methylpropane sulphonic acid, and methylene bisacrylamide. The developed chemically crosslinked nanogels were characterized by FTIR, SEM, PXRD, TGA, DSC, sol-gel analysis, zeta size, micromeritics properties, drug loading percentage, swelling, solubility, and release studies. The FTIR spectrum depicts the leading peaks of resultant functional groups of blended constituents while a fluffy and porous structure was observed through SEM images. Remarkable reduction in crystallinity of RST in developed nanogels revealed by PXRD. TGA and DSC demonstrate the good thermal stability of nanogels. The size analysis depicts the particle size of the developed nanogels in the range of 178.5 ±3.14 nm. Drug loading percentage, swelling, solubility, and release studies revealed high drug loading, solubilization, swelling, and drug release patterns at 6.8 pH paralleled to 1.2 pH. In vivo experiments on developed nanogels in comparison to marketed brands were examined and better results regarding pharmacokinetic parameters were observed. The compatibility and non-toxicity of fabricated nanogels to biological systems was supported by a toxicity study that was conducted on rabbits. Efficient fabrication, excellent physicochemical properties, improved dissolution, high solubilization, and nontoxic nanogels might be a capable approach for the oral administration of poorly water-soluble drugs.

Optimization of Novel Naproxen-Loaded Chitosan/Carrageenan Nanocarrier-Based Gel for Topical Delivery: Ex Vivo, Histopathological, and In Vivo Evaluation.

Naproxen (NAP) is commonly used for pain, inflammation, and stiffness associated with arthritis. However, systemic administration is linked with several gastrointestinal tract (GIT) side effects. The present work aims to prepare and evaluate NAP nanoparticulate shells of chitosan (CS) and carrageenan (CRG) loaded into a Carbopol 940 (Ca-940) gel system with unique features of sustained drug delivery as well as improved permeation through a topical route. Moreover, this study aims to evaluate its ex vivo, histopathological, and in vivo anti-inflammatory activity in albino Wistar rats. The percentage of ex vivo drug permeation patterns in the optimized formulation (No) was higher (88.66%) than the control gel (36.195%). Oral toxicity studies of developed nanoparticles in albino rabbits showed that the NAP-loaded CS/CRG are non-toxic and, upon histopathological evaluation, no sign of incompatibility was observed compared to the control group. A In Vivo study showed that the optimized gel formulation (No) was more effective than the control gel (Nc) in treating arthritis-associated inflammation. The sustained permeation and the absence of skin irritation make this novel NAP nanoparticle-loaded gel based on CS/CRG a suitable drug delivery system for topical application and has the potential for improved patient compliance and reduced GIT-related side effects in arthritis.

Hydrogels as potential drug-delivery systems: network design and applications.

Hydrogels are 3D crosslinked polymer matrices having a colossal tendency to imbibe water and exhibit swelling under physiological conditions without deformation in their hydrophilic network. Hydrogels being biodegradable and biocompatible, gained consideration due to some unique characteristics: responsiveness to external stimuli (pH, temperature) and swelling in aqueous solutions. Hydrogels offer a promising option for various pharmaceutical and biomedical applications, including tissue-specific drug delivery at a predetermined, controlled rate. This article presents a brief review of the recent and fundamental advances to design hydrogels, the swelling and deswelling mechanism, various crosslinking methods and their use as an intelligent carrier in the pharmaceutical field. Recent applications of hydrogels are also briefly discussed and exemplified.

Seroprevalence and Risk Factors of Toxoplasma gondii in Wild Birds of Punjab Province, Pakistan.

Toxoplasma gondii is a protozoan parasite of veterinary and human public health importance for which birds act as an intermediate host. No information is available about the epidemiology of T. gondii in wild birds of Pakistan. The present study was designed to determine the seroprevalence and risk factors associated with T. gondii antibodies in wild birds of District Kasur, Punjab Province, Pakistan. A total of 200 wild birds of 28 species were captured from four tehsils (administrative subdistricts of districts) of the district Kasur and their serum samples screened for the presence of T. gondii antibodies using a latex agglutination test (cut-off value: 1:64). Twenty-five (13%) individual birds and 13 (46%) of the bird species were seropositive for T. gondii antibodies. There were statistical differences in T. gondii prevalence between adults and young (15% and 7%, respectively, P=0.001) and healthy and sick (11% and 50%, respectively, P=0.000) while there were not differences between genders, sites, urbanicity, and tehsils. The present study provides evidence of T. gondii antibodies in wild birds of Pakistan.

Development and Characterization of Olanzapine Loaded Poly(lactide-coglycolide) Microspheres for Depot Injection: In vitro and In vivo Release Profiles.

PURPOSE: The purpose of this study was to develop a new PLGA based microsphere formulation aimed to release the olanzapine for the period of one month which will result in increased compliance. METHODS: Microspheres loaded with olanzapine were prepared using oil in water emulsion and solvent evaporation technique. The microspheres were characterized by surface morphology, shape, size, bulk density, encapsulation efficiency, and Fourier transform infrared spectrometry. In vitro release studies were performed in phosphate buffer at 37°C and in vivo studies were conducted on male Sprague- Dawley rats. RESULTS: The morphological results indicated that microspheres produced were having a smooth surface, spherical shape and the size in the range from 9.71 to 19.90 µm mean diameter. Encapsulation efficiency of olanzapine loaded microspheres was in the range of 78.53 to 96.12% and was affected by changing the ratio of lactic to glycolic acid in copolymer PLGA. The properties of PLGA and other formulation parameters had a significant impact on in vitro and in vivo release of drug from microspheres. In vitro release kinetics revealed that release of drug from microspheres is by both non-Fickian diffusion and erosion of PLGA polymer. In vivo data indicated an initial burst release and then sustained release depending on properties of PLGA, microsphere size, and bulk density. CONCLUSION: This study indicates that microsphere formulations developed with PLGA (75:25) and PLGA (85:15) have provided a sufficient steady release of drug for at least 30 days and can be potential candidates for 30-day depot injection drug delivery of olanzapine.

Carrageenan Based Bionanocomposites as Drug Delivery Tool with Special Emphasis on the Influence of Ferromagnetic Nanoparticles.

Over the past few years, considerable attention has been focused on carrageenan based bionanocomposites due to their multifaceted properties like biodegradability, biocompatibility, and nontoxicity. Moreover, these composites can be tailored according to the desired purpose by using different nanofillers. The role of ferromagnetic nanoparticles in drug delivery is also discussed here in detail. Moreover, this article also presents a short review of recent research on the different types of the carrageenan based bionanocomposites and applications.

A QUALITY BY DESIGN APPROACH: FABRICATION, CHARACTERIZATION AND EVALUATION OF OPTIMIZED TRANSDERMAL THERAPEUTIC SYSTEM FOR ANTIRHEUMATIC LORNOXICAM.

Microemulsion was prepared using several concentrations of selected oil (pine oil), surfactant (cre- mophor RH40), co-surfactant (isopropanol) and water to improve bioavailability by increasing solubility and permeability of lomoxicam, which was then incorporated to carbomer 940 gel base to fabricate microemulsion based gel (MEBG) to sustained permeability for transdermal delivery. Initially, the formulations were investi- gated for physicochemical characteristics, i.e., pH, conductivity, viscosity, refractive index, zeta size, poly-dis- persity index and Atomic Force Microscopy. Also, the significance of the components on in vitro permeability was observed to find out optimum microemulsion (ME,) using Box-Behnken-Design (BBD). MEBG was com- pared for in vitro permeation, stability, skin irritation and anti-inflammatory studies using control gel and in vivo bioavailability study with oral tablet. Microemulsions exhibited the physiological pH (5.35-5.99), oil in water nature (139-185 tsiemens/cm), isotropic (1.3390-1.4166), narrow size (62 nm), homogeneity, Newtonian flow (52-160 centipoise) and spherical shape. Predicted values (Q2, flux, lag time) of optimized microemulsions derived from BBD were in reasonable agreement with experimental values. The formulations were stable and non-irritating to the skin. Significant difference was investigated when comparing percent inhibition of edema of MEBG (80%) and control gel (40%) with respect to standard. The MEBG behavior differed significantly from oral tablet formulation in vivo bioavailability. Such BBD based estimation will reduce time and cost in drug designing, delivery and targeting.

Fine-grained dengue forecasting using telephone triage services.

Thousands of lives are lost every year in developing countries for failing to detect epidemics early because of the lack of real-time disease surveillance data. We present results from a large-scale deployment of a telephone triage service as a basis for dengue forecasting in Pakistan. Our system uses statistical analysis of dengue-related phone calls to accurately forecast suspected dengue cases 2 to 3 weeks ahead of time at a subcity level (correlation of up to 0.93). Our system has been operational at scale in Pakistan for the past 3 years and has received more than 300,000 phone calls. The predictions from our system are widely disseminated to public health officials and form a critical part of active government strategies for dengue containment. Our work is the first to demonstrate, with significant empirical evidence, that an accurate, location-specific disease forecasting system can be built using analysis of call volume data from a public health hotline.

DEVELOPMENT OF OLANZAPINE LOADED PNA MICROGELS FOR DEPOT DRUG DELIVERY IN TREATMENT OF SCHIZOPHRENIA: IN VITRO AN IN VIVO RELEASE PROFILE.

Schizophrenia is a lifelong debilitating illness requiring extended treatment with antipsychotic agents. Non-adherence to therapy is a very common and severe problem in these patients, which can be improved by prescribing depot injectable or implant formulations. The purpose of this study was to develop PNA microgels based in situ gelling system for sustained release of olanzapine. PNA [poly(N-isopropylacrylamide-co-acrylic acid)] microgels were prepared using a previously developed method employing emulsion polymerization technique, applying one of the optimized formulations. Olanzapine loaded PNA microgels were characterized by viscosity measurements, cytotoxicity assay and TEM analysis. In vitro release of olanzapine from PNA microgels was determined on different pH and temperature range. In vivo studies were performed on male Sprague-Dawley rats with average weight of 315 g (n = 6). Olanzapine loaded PNA microgels were successfully prepared with drug loading efficiency of 2.14 ± 0.52%. The fluid like viscosity of microgels formulation at lower pH value (pH 5.0) and room as well as body temperature made it favorable for injection form. In vitro release was characterized by a high initial burst release up to 38.6% of the drug release within 2 h. In vivo release data also indicated similar initial high burst release that might indicate toxicity when administered in injectable dosage form but subcutaneous injection of PNA microgels proved fruitful results as this initial burst release followed a sustained release for 72 h. Hence, PNA microgels can be formulated for short term depot injection, which can potentially provide the release of olanzapine for 72 h.

Evaluation of Hormone Receptor Status (ER/PR/HER2-neu) in Breast Cancer in Pakistan.

OBJECTIVE: To evaluate the biological markers that are commonly assessed in breast cancer to estimate a patient's response to endocrine therapy and their prognosis for better clinical outcomes. METHODS: The retrospective study was conducted at Bahawalpur Institute of Nuclear Oncology and comprised record of early breast cancer patients who gave positive diagnostic tests for hormone receptors status i.e. immunohistochemical test and were treated during 2007-2013. Data of oestrogen, progesterone and human epidermal growth factor receptor 2 expression status was analysed. SPSS 12 was used for statistical analysis. RESULTS: Overall record of 345 patients was studied of whom 149(43%) were identified to have positive hormone receptor status.. The age of the patients ranged from 24 to 86 years with 97(65%) in 25-50 years, 46(30.8%) 51-75 years and 6(4.08%)in 76-100 years. Besides, 76(51%) patients had carcinoma of right breast; 86(58%) were diagnosed as Stage III, 55(37%) Stage II and 8(5.3%) Stage IV. Those diagnosed with oestrogen receptor (positive status) were 16(10.7%), human epidermal growth factor receptor 2 over-expression 13(8.7%), oestrogen/progesterone hormone receptor positivity (or luminal A) 76(51%) and 35(23.4%) patients were positive for all the three receptors. CONCLUSIONS: About half of the patients were diagnosed with a positive hormone status and it was observed that in most of the cases disease was metastasised to distant organs.

FluBreaks: early epidemic detection from Google flu trends.

BACKGROUND: The Google Flu Trends service was launched in 2008 to track changes in the volume of online search queries related to flu-like symptoms. Over the last few years, the trend data produced by this service has shown a consistent relationship with the actual number of flu reports collected by the US Centers for Disease Control and Prevention (CDC), often identifying increases in flu cases weeks in advance of CDC records. However, contrary to popular belief, Google Flu Trends is not an early epidemic detection system. Instead, it is designed as a baseline indicator of the trend, or changes, in the number of disease cases. OBJECTIVE: To evaluate whether these trends can be used as a basis for an early warning system for epidemics. METHODS: We present the first detailed algorithmic analysis of how Google Flu Trends can be used as a basis for building a fully automated system for early warning of epidemics in advance of methods used by the CDC. Based on our work, we present a novel early epidemic detection system, called FluBreaks (dritte.org/flubreaks), based on Google Flu Trends data. We compared the accuracy and practicality of three types of algorithms: normal distribution algorithms, Poisson distribution algorithms, and negative binomial distribution algorithms. We explored the relative merits of these methods, and related our findings to changes in Internet penetration and population size for the regions in Google Flu Trends providing data. RESULTS: Across our performance metrics of percentage true-positives (RTP), percentage false-positives (RFP), percentage overlap (OT), and percentage early alarms (EA), Poisson- and negative binomial-based algorithms performed better in all except RFP. Poisson-based algorithms had average values of 99%, 28%, 71%, and 76% for RTP, RFP, OT, and EA, respectively, whereas negative binomial-based algorithms had average values of 97.8%, 17.8%, 60%, and 55% for RTP, RFP, OT, and EA, respectively. Moreover, the EA was also affected by the region's population size. Regions with larger populations (regions 4 and 6) had higher values of EA than region 10 (which had the smallest population) for negative binomial- and Poisson-based algorithms. The difference was 12.5% and 13.5% on average in negative binomial- and Poisson-based algorithms, respectively. CONCLUSIONS: We present the first detailed comparative analysis of popular early epidemic detection algorithms on Google Flu Trends data. We note that realizing this opportunity requires moving beyond the cumulative sum and historical limits method-based normal distribution approaches, traditionally employed by the CDC, to negative binomial- and Poisson-based algorithms to deal with potentially noisy search query data from regions with varying population and Internet penetrations. Based on our work, we have developed FluBreaks, an early warning system for flu epidemics using Google Flu Trends.

Comparative bioavailability and pharmacokinetics of investigational enteric- and film-coated formulations of flurbiprofen 100-mg tablets: a single-dose, randomized, open-label, two-period, two-way crossover study in healthy Pakistani male volunteers.

BACKGROUND: Flurbiprofen, a chiral, 2-arylpropionic acid NSAID with analgesic and antipyretic properties, has been associated with important gastrointestinal adverse events, including peptic ulcer and gastrointestinal perforation. An investigational enteric-coated tablet formulation of flurbiprofen was produced to evaluate whether it would improve the gastric tolerability of flurbiprofen. OBJECTIVE: This study compared the pharmacokinetic parameters and bioavailability of flurbiprofen from the investigational enteric-coated tablet (test) and from a film-coated immediate-release tablet compounded for the purposes of this study (reference). METHODS: This was a randomized, open-label, 2-period, 2-way crossover study conducted in healthy male volunteers at a single center in Pakistan. Small batches of the test and reference tablets were manufactured and evaluated according to US Pharmacopoeia criteria. Each volunteer received a single 100-mg tablet of the test and reference formulations, separated by a 14-day washout period. Tablets were administered after an overnight fast. Blood samples were obtained before dosing (0) and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours after drug administration. Safety monitoring was performed by an unblinded physician and included adverse events, biochemistry and hematology tests, urinalysis, and ECGs. Plasma concentrations of the 2 formulations were determined, and pharmacokinetic parameters were compared using noncompartmental analysis. The 2 formulations were considered bioequivalent if the 90% CI for the ratios (test:reference) of log-transformed C(max), AUC(0-t), and AUC(0-infinity) were between 0.80 and 1.25. RESULTS: Of the 23 healthy male subjects originally recruited, 2 withdrew before commencement of the study. Twenty-one subjects (mean [SD] age, 25.4 [2.7] years [range, 20-30 years]; weight, 63.4 [7.2] kg [range, 56-78 kg]) were enrolled in and completed the study. There were significant differences in C(max), AUC(0-t), and AUC(0-infinity) between the test and reference formulations (all, P < 0.001). The 90% CIs for the geometric mean ratios of log-transformed C(max), AUC(0-t), and AUC(0-infinity) (49.78-55.22, 57.51-64.42, and 58.48-65.30, respectively) were not within the predetermined bioequivalence range. There were no clinically meaningful changes in hematology, biochemistry, urinalysis, or physical variables with either formulation over the course of the study. Mild headache was reported in 2 volunteers who received the reference formulation during the first study period; this was not considered related to study drug. CONCLUSIONS: In this small study in healthy Pakistani male subjects, there were significant differences in the bioavailability and pharmacokinetic parameters of the enteric- and film-coated tablet formulations of flurbiprofen. Thus, the 2 formulations could not be considered bioequivalent. Both formulations were well tolerated.