AS1411 aptamer/RGD dual functionalized theranostic chitosan-PLGA nanoparticles for brain cancer treatment and imaging.

Conventional chemotherapy and poor targeted delivery in brain cancer resulting to poor treatment and develop resistance to anticancer drugs. Meanwhile, it is quite challenging to diagnose/detection of brain tumor at early stage of cancer which resulting in severity of the disease. Despite extensive research, effective treatment with real-time imaging still remains completely unavailable, yet. In this study, two brain cancer cell specific moieties i.e., AS1411 aptamer and RGD are decorated on the surface of chitosan-PLGA nanoparticles to improve targeted co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) for effective brain tumor therapy and real-time imaging. The nanoparticles were developed by a slightly modified emulsion/solvent evaporation method. This investigation also translates the successful synthesis of TPGS-chitosan, TPGS-RGD and TPGS-AS1411 aptamer conjugates for making PLGA nanoparticle as a potential tool of the targeted co-delivery of DTX and UCNP to the brain cancer cells. The developed nanoparticles have shown an average particle size <200 nm, spherical in shape, high encapsulation of DTX and UCNP in the core of nanoparticles, and sustained release of DTX up to 72 h in phosphate buffer saline (pH 7.4). AS1411 aptamer and RGD functionalized theranostic chitosan-PLGA nanoparticles containing DTX and UCNP (DUCPN-RGD-AS1411) have achieved greater cellular uptake, 89-fold improved cytotoxicity, enhanced cancer cell arrest even at lower drug conc., improved bioavailability with higher mean residence time of DTX in systemic circulation and brain tissues. Moreover, DUCPN-RGD-AS1411 have greatly facilitated cellular internalization and higher accumulation of UCNP in brain tissues. Additionally, DUCPN-RGD-AS1411 demonstrated a significant suppression in tumor growth in brain-tumor bearing xenograft BALB/c nude mice with no impressive sign of toxicities. DUCPN-RGD-AS1411 has great potential to be utilized as an effective and safe theranostic tool for brain cancer and other life-threatening cancer therapies.

Technical Considerations, Applications, and Benefits of Organogels in Topical Drug Delivery Systems.

Organogels represent semi-solid systems where an organic liquid phase is entrapped within a three-dimensional network formed by self-assembled, crosslinked, or entangled gelator fibers. These versatile materials find applications in a wide range of fields, including chemistry, pharmaceuticals, cosmetics, biotechnology, and food technology. Notably, in pharmacology, they serve as valuable platforms for drug and vaccine delivery, facilitating the transport of active ingredients through various routes such as transdermal, oral, and parenteral. However, their previous utility as drug delivery systems was hindered by the toxicity associated with the organic solvents used. The pharmacokinetics of medications delivered via organogels are primarily influenced by the distinctive properties of these materials, specifically their "high permeability and poor aqueous solubility," which can impact the bioavailability of the drugs. Organogels can be employed topically or for the controlled release of medications through cutaneous administration and percutaneous absorption, expanding their scope of application beyond conventional drug delivery methods. Organogels hold significant promise as drug delivery vehicles due to their biocompatibility, non-irritating properties, and thermoremanent characteristics. They enable the formulation of diverse drug delivery systems by incorporating both hydrophilic and hydrophobic bioactive compounds within the gel matrix. This comprehensive review offers an overview of organogels, encompassing their nature, synthesis, characterization, and properties. Special attention is directed towards cutting-edge technologies employed in designing organogels as potential controlled delivery systems, with a focus on their emerging therapeutic applications.

Exploring the Therapeutic Potential of Phytoconstituents for Addressing Neurodegenerative Disorders.

Neurodegenerative disorder is a serious condition that is caused by abnormal or no neurological function. Neurodegenerative disease is a major growing cause of mortality and morbidity worldwide, especially in the elderly. After World War Ⅱ, eugenics term was exterminated from medicines. Neurodegenerative disease is a genetically inherited disease. Lifestyle changes, environmental factors, and genetic modification, together or alone, are involved in the occurrence of this disorder. The major examples of neurodegenerative disorders are Alzheimer's and Parkinson's disease, in which apoptosis and necrosis are the two major death pathways for neurons. It has been determined from various studies that the etiology of the neurodegenerative disease involves the role of oxidative stress and anti-oxidant defence system, which are prime factors associated with the activation of signal transduction pathway that is responsible for the formation of synuclein in the brain and manifestation of toxic reactions in the form of functional abnormality, which ultimately leads to the dysfunction of neuronal pathway or cell. There has not been much success in the discovery of effective therapy to treat neurodegenerative diseases because the main cause of abnormal functioning or death of neurons is not well known. However, the use of natural products that are derived from plants has effective therapeutic potential against neurodegenerative disease. The natural compounds with medicinal properties to prevent neurological dysfunction are curcumin, wolfberry, ginseng, and Withania somnifera. The selection and use of natural compounds are based on their strong anti-inflammatory and anti-oxidant properties against neurodegenerative disease. Herbal products have active constituents that play an important role in the prevention of communication errors between neurons and neurotransmitters and their respective receptors in the brain, which influence their function. Considering this, natural products have great potential against neurodegenerative diseases. This article reviews the natural compounds used to treat neurodegenerative diseases and their mechanisms of action.

Isolation, characterization, and evaluation of anxiolytic bioactive compounds from the seed of Vigna radiata (L.) R. Wilczek in mice.

Recent therapy for managing anxiety disorders is linked with a wide range of adverse effects. The conventional practice of the use of plant extract may indicate an important and new approach to the anxiolytic agent. Seeds of V. radiata belonging to the family Fabaceae is commonly employed to treat several diseases. However, no data is available to screen its viable neuropharmacological effect regardless of its famous use. Hence, the objective of the present study was to isolate the anxiolytic bioactive compound from seeds of V. radiata. Pure bioactive Compounds SU1 and SU2 were obtained from bioactive fraction F9.3 and fraction F9.5 using the bioactivity-guided fractionation method. The current investigation found that 4 mg/kg (o.p.) of kaempferol and γ-aminobutyric acid exhibit significant anxiolytic action in mice that is statistically comparable to diazepam (2 mg/kg.i.p). This study validates the ethnopharmacological use of V. radiata seeds in the management of anxiety disorders.

An Overview of Current Progress and Challenges in Brain Cancer Therapy Using Advanced Nanoparticles.

Brain tumors pose significant challenges in terms of complete cure and early-stage prognosis. The complexity of brain tumors, including their location, infiltrative nature, and intricate tumor microenvironment (TME), contributes to the difficulties in achieving a complete cure. The primary objective of brain cancer therapy is to effectively treat brain tumors and improve the patient's quality of life. Nanoparticles (NPs) have emerged as promising tools in this regard. They can be designed to deliver therapeutic drugs to the brain tumor site while also incorporating imaging agents. The NPs with the 10-200 nm range can cross the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) and facilitate drug bioavailability. NPs can be designed by several methods to improve the pharmaceutical and pharmacological aspects of encapsulated therapeutic agents. NPs can be developed in various dosage forms to suit different administration routes in brain cancer therapy. The unique properties and versatility of NPs make them essential tools in the fight against brain tumors, offering new opportunities to improve patient outcomes and care. Having the ability to target brain tumors directly, overcome the BBB, and minimize systemic side effects makes NPs valuable tools in improving patient outcomes and care. The review highlights the challenges associated with brain tumor treatment and emphasizes the importance of early detection and diagnosis. The use of NPs for drug delivery and imaging in brain tumors is a promising approach to improving patient outcomes and quality of life. The versatility and unique properties of NPs make them valuable tools in the fight against brain tumors, and NPs have the potential to revolutionize healthcare.

Dual-targeted transferrin and AS1411 aptamer conjugated micelles for improved therapeutic efficacy and imaging of brain cancer.

Brain tumors represent an aggressive form of cancer, posing significant challenges in achieving complete remission. Development of advanced therapies is crucial for improving clinical outcomes in cancer patients. This study aimed to create a novel treatment approach using dual-targeted transferrin (TF) and AS1411 conjugated micelles, designed to enhance therapeutic effectiveness of docetaxel (DTX) and facilitate gadolinium (Gd) based imaging in brain cancer. Micelles were prepared using a slightly modified solvent-casting method, and the dual-targeting ligands were attached to the micelle's surface through a physical adsorption process. Average particle size of micelles ranged from 117.49 ± 3.90-170.38 ± 3.39 nm, with a low polydispersity index. Zeta potential ranged from - 1.5 ± 0.02 to - 18.7 ± 0.04 mV. Encapsulation efficiency of DTX in micelles varied from 92.64 ± 4.22-79.77 ± 4.13 %. Simultaneously, encapsulation of Gd in micelles was found to be 48.27 ± 3.18-58.52 ± 3.17, respectively. In-vitro drug release studies showed a biphasic sustained release profile, with DTX and Gd release continuing up to 72 h with their t50 % at 4.95, 11.29, and 24.14 h for GDTP, GDTP-TF and GDTP-TF-AS1411 micelles, respectively. Cytotoxicity effect of GDTP-TF-AS1411 micelles has shown significant improvement (P < 0.001) and reduced IC50 value up to 0.19 ± 0.14 µg/ml compared to Taxotere® (2.73 ± 0.73 µg/ml). Theranostic study revealed higher accumulation of GDTP-TF and GDTP-TF-AS1411 micelles free GD treated animal brains. The AUC of GDTP-TF-AS1411 micelles exhibited 23.79 ± 17.82 µg.h/ml higher than Taxotere® (14.14 ± 10.59 µg.h/ml). These findings direct enhanced effectiveness in brain cancer therapy leading to improved therapeutics in brain cancer patients. The combined targeted ligands and therapeutic agents strategy can direct advancement in brain cancer therapy and offer improved therapy for patients.

An Overview of Metallic Nanoparticles: Classification, Synthesis, Applications, and their Patents.

BACKGROUND: Nanotechnology has gained enormous attention in pharmaceutical research. Nanotechnology is used in the development of nanoparticles with sizes ranging from 1-100nm, with several extraordinary features. Metallic nanoparticles (MNPs) are used in various areas, such as molecular biology, biosensors, bio imaging, biomedical devices, diagnosis, pharmaceuticals, etc., for their specific applications. METHODOLOGY: For this study, we have performed a systematic search and screening of the literature and identified the articles and patents focusing on various physical, chemical, and biological methods for the synthesis of metal nanoparticles and their pharmaceutical applications. RESULTS: A total of 174 references have been included in this present review, of which 23 references for recent patents were included. Then, 29 papers were shortlisted to describe the advantages, disadvantages, and physical and chemical methods for their synthesis, and 28 articles were selected to provide the data for biological methods for the formulation of metal NPs from bacteria, algae, fungi, and plants with their extensive synthetic procedures. Moreover, 27 articles outlined various clinical applications of metal NPs due to their antimicrobial and anticancer activities and their use in drug delivery. CONCLUSION: Several reviews are available on the synthesis of metal nanoparticles and their pharmaceutical applications. However, this review provides updated research data along with the various methods employed for their development. It also summarizes their various advantages and clinical applications (anticancer, antimicrobial drug delivery, and many others) for various phytoconstituents. The overview of earlier patents by several scientists in the arena of metallic nanoparticle preparation and formulation is also presented. This review will be helpful in increasing the current knowledge and will also inspire to innovation of nanoparticles for the precise and targeted delivery of phytoconstituents for the treatment of several diseases.

Effect of Extraction Methods on the Antioxidant Potential and Cytotoxicity of the Combined Ethanolic Extracts of Daucus carota L., Beta vulgaris L., Phyllanthus emblica L. and Lycopersicon esculentum against Gastric Adenocarcinoma Cells.

Frequent consumption of fruits and vegetables in the daily diet may alleviate the risk of developing chronic diseases. Daucus carota L. (carrot), Beta vulgaris L. (beetroot) Phyllanthus emblica L. (amla), and Lycopersicon esculentum M (tomatoes) are traditionally consumed functional foods that contain a high concentration of antioxidants, ascorbic acid, polyphenols, and numerous phytochemicals. This study assessed how three distinct preparation methods affect the phenolic, flavonoid, carotenoid, and ascorbic acid contents, antioxidant level, and cytotoxicity of the combined fruit extract. The fruit samples were taken in the ratio of carrot (6): beetroot (2): tomato (1.5): amla (0.5) and processed into a lyophilized slurry (LS) extract, lyophilized juice (LJ) extract, and hot-air oven-dried (HAO) extract samples. The sample extracts were assessed for their phytoconstituent concentrations and antioxidant and cytotoxic potential. The total phenolic content in LS, LJ, and HAO extracts was 171.20 ± 0.02, 120.73 ± 0.02, and 72.05 ± 0.01 mg gallic acid equivalent/100 g, respectively and the total flavonoid content was 23.635 ± 0.003, 20.754 ± 0.005, and 18.635 ± 0.005 mg quercetin equivalent/100 g, respectively. Similarly, total ascorbic acid content, carotenoids, and antioxidant potential were higher in the LS and LJ extracts than in HAO. Overall, the LS extract had a substantially higher concentration of phytochemicals and antioxidants, as well as higher cytotoxic potential, compared to the LJ and HAO extracts. The LS extract was tested in the MKN-45 human gastric cancer cell line to demonstrate its effective antioxidant potential and cytotoxicity. Hence, lyophilization (freezing) based techniques are more effective than heat-based techniques in preserving the phytoconstituents and their antioxidant and cytotoxic potential.

Nano Architect-Based Targeted Delivery Systems for Diabetic Nephropathy: A Review.

Diabetes mellitus is a long-lasting disease that is very common in the age group above 20 years and is characterized by hyperglycemia with other complications like Diabetic Nephropathy (DN). The management of DN focuses on mainly four regions: reduction of cardiovascular risks, control of blood glycemic levels, control of the blood pressure (BP) profile, and the use of therenin-angiotensin system (RAS). Although BP management and RAS-acting agents can postpone the onset of DN, they cannot prevent it. In the modern era, nanotechnological interventions have spread rapidly in the field of medicine. Patient defiance is considered important in diabetes management when long-term or continuous management is required. Nano pharmaceuticals have been shown to increase compliance of diabetic patients by providing multiple ways of drug delivery, controlling release profile, increasing biological steadiness, targeting efficacy, and decreasing toxic profile. Nanoscale formulations of botanical antidiabetic molecules improve clinical efficacy and treatment compliance by overcoming associated biopharmaceutical and pharmacokinetic barriers. Therefore, the development of nanopharmaceuticals can be considered to be a possible answer to attain the finest scientific effect of the plant-based anti-diabetic molecule. Nevertheless, further studies are needed to create clinical research-based and therapeutically effective nanoforms of antidiabetic plant-based molecules to combat the most dreaded disease of diabetes and its known present complications.

RGD-decorated PLGA nanoparticles improved effectiveness and safety of cisplatin for lung cancer therapy.

Upon extensive pharmaceutical and biomedical research to treat lung cancer indicates that lung cancer remains one of the deadliest diseases and the leading cause of death in men and women worldwide. Lung cancer remains untreated and has a high mortality rate due to the limited potential for effective treatment with existing therapies. This highlights the urgent need to develop an effective, precise and sustainable solutions to treat lung cancer. In this study, we developed RGD receptor-targeted PLGA nanoparticles for the controlled and targeted co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) in lung cancer therapy. Pluronic F127-RGD conjugate was synthesized by carbodiimide chemistry method and the conjugation was confirmed by FTIR and 1HNMR spectroscopy techniques. PLGA nanoparticles were developed by the double emulsification method, then the surface of the prepared nanoparticles was decorated with Pluronic F127-RGD conjugate. The prepared formulations were characterized for their particle size, polydispersity index, zeta potential, surface morphology, drug encapsulation efficiency, and in vitro drug release and haemolysis studies. Pharmacokinetic studies and safety parameters in BAL fluid were assessed in rats. Histopathology of rat lung tissue was performed. The obtained results of particle sizes of the nanoparticle formulations were found 100-200 nm, indicating the homogeneity of dispersed colloidal nanoparticles formulations. Transmission Electron Microscopy (TEM) revealed the spherical shape of the prepared nanoparticles. The drug encapsulation efficiency of PLGA nanoparticles was found to range from 60% to 80% with different nanoparticles counterparts. RGD receptor-targeted PLGA nanoparticles showed controlled drug release for up to 72 h. Further, RGD receptor-targeted PLGA nanoparticles achieved higher cytotoxicity in compared to CFT, CFT, and Ciszest-50 (marketed CDDP injection). The pharmacokinetic study revealed that RGD receptor-targeted PLGA nanoparticles were 4.6-fold more effective than Ciszest-50. Furthermore, RGD receptor-targeted PLGA nanoparticles exhibited negligible damage to lung tissue, low systemic toxicity, and high biocompatible and safety in lung tissue. The results of RGD receptor-targeted PLGA nanoparticles indicated that it is a promising anticancer system that could further exploited as a potent therapeutic approach for lung cancer.

An Electronic Evaluation of Symptoms in People of India Post-COVID-19 Vaccination.

BACKGROUND: Remarkable and groundbreaking performances of scientists all over the globe have led to the evolution of COVID-19 vaccines, which are extensively viewed as means to control the epidemic. The primary purpose of this research work was to discover the major side effects of the vaccines, mainly in Homo sapiens. METHODS: An online survey was conducted in various cities of Haryana, India, using a trial version of QualtricsCoreXM software to prototype 20 questionnaires. RESULTS: In the survey, 200 candidates participated, among which 83.5% had received Covishield and 16.5% had been vaccinated with Covaxin. Overall 65% of respondents have reported side effects. The major side effects reported were fever, tiredness, myalgia, diarrhea, headache, etc. Conclusion: Succeeding the survey related to the effects of COVID-19 vaccine on non-identical Homo sapiens, generally with respect to their perspective regarding the symptoms of vaccine, both the vaccines were found to have mild side effects which could be easily managed.

Nanocapsules: An Emerging Drug Delivery System.

BACKGROUND: Controlled drug release and site-specific delivery of drugs make nanocapsules the most approbative drug delivery system for various kinds of drugs, bioactive, protein, and peptide compounds. Nanocapsules (NCs) are spherical shape microscopic shells consisting of a core (solid or liquid) in which the drug is positioned in a cavity enclosed by a distinctive polymeric membrane. OBJECTIVES: The main objective of the present patent study is to elaborate on various formulation techniques and methods of nanocapsules (NCs). The review also spotlights various biomedical applications as well as on the patents of NCs to date. METHODS: The review was extracted from the searches performed using various search engines such as PubMed, Google Patents, Medline, Google Scholars, etc. In order to emphasize the importance of NCs, some published patents of NCs have also been reported in the review. RESULTS: NCs are tiny magical shells having incredible reproducibility. Various techniques can be used to formulate NCs. The pharmaceutical performance of the formulated NCs can be judged by evaluating their shape, size, entrapment efficiency, loading capacity, etc., using different analytical techniques. Their main applications are found in the field of agrochemicals, genetic manipulation, cosmetics, hygiene items, strategic distribution of drugs to tumors, nanocapsule bandages to combat infection, and radiotherapy. CONCLUSION: In the present review, our team made a deliberate effort to summarize the recent advances in the field of NCs and focus on new patents related to the implementation of NCs delivery systems in the area of some life-threatening disorders like diabetes, cancer, and cardiovascular diseases.

Design and Molecular Docking Studies of N-Mannich Base Derivatives of Primaquine Bearing Isatin on the Targets involved in the Pathophysiology of Cerebral Malaria.

BACKGROUND: Malaria is considered one of the life-threatening mosquito-borne infectious diseases responsible for approximately more than 4,00,000 deaths every year all over the world. Plasmodium falciparum and Plasmodium vivax are widespread species, but infections caused by the former are of great concern. OBJECTIVE: Among the various forms of infections associated with Plasmodium falciparum, cerebral malaria (CM) is the most severe neurological complication, accounting for almost 13% of all malariarelated mortality. The development of effective therapeutics is urgently needed to overcome the fatality of this dreadful disease. METHODS: The present work attempted to design and virtually screen a chemical library of 75 molecules (N-Mannich base derivatives of primaquine bearing isatin moiety as heterocyclic) by molecular docking studies against anti-malarial target proteins-Cystein Protease Falcipain-2; Dipeptidyl Aminopeptidase- 1; Dipeptidyl Aminopeptidase-3 and Glycogen synthase Kinase-3ß receptors, for evaluating their anti-malarial potential. Among all studied anti-malarial target receptors, the designed molecules showed an overall higher affinity for Dipeptidyl Aminopeptidase-3. Furthermore, the molecules were analyzed for binding affinity and drug-like properties using Lipinski rules, and 30 best hits were shortlisted and analyzed for the pharmacokinetic profile. RESULTS: Two of these hits were found to be more toxic than primaquine, hence were omitted in further analysis. Later, these 28 hits were docked against two target proteins, (a) Plasmodium falciparum erythrocyte membrane protein-1 and (b) Intracellular adhesion molecule-1, to determine their efficiency against cerebral malaria, and the results were recorded. Analysis of docking results led to the identification of the 8 studied molecules as lead molecules which were selected for chemical synthesis, in vivo studies, and further preclinical evaluation. CONCLUSION: The molecule DSR 11 was predicted as the most appropriate lead molecule for anti-CM activity in the present investigation apart from the other seven molecules (DSR4, DSR26, DSR38, DSR40, DSR49, DSR56, and DSR70).

Safety, immunogenicity & effectiveness of the COVID-19 vaccine among healthcare workers in a tertiary care hospital.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic has caused significant global morbidity and mortality. As the vaccination was rolled out with prioritization on healthcare workers (HCWs), it was desirable to generate evidence on effectiveness of vaccine in prevailing real-life situation for policy planning. The objective of the study was to evaluate the safety, effectiveness and immunogenicity of COVID-19 vaccination among HCWs in a tertiary care hospital. METHODS: This prospective observational study was undertaken on the safety, immunogenicity and effectiveness of the ChAdOx1 nCoV- 19 coronavirus vaccine (Recombinant) during the national vaccine roll out in January-March 2021, in a tertiary care hospital, New Delhi, India. RESULTS: The vaccine was found to be safe, with local pain, fever and headache as the most common adverse events of milder nature which generally lasted for two days. The adverse events following vaccination were lower in the second dose as compared to the first dose. The vaccine was immunogenic, with seropositivity, which was 51 per cent before vaccination, increasing to 77 per cent after single dose and 98 per cent after two doses. Subgroup analysis indicated that those with the past history of COVID-19 attained seropositivity of 98 per cent even with single dose. The incidence of reverse transcription (RT)-PCR positive COVID-19 was significantly lower among vaccinated (11.7%) as compared to unvaccinated (22.2%). Seven cases of moderate COVID-19 needing hospitalization were seen in the unvaccinated and only one such in the vaccinated group. The difference was significant between the fully vaccinated (10.8%) and the partially vaccinated (12.7%). The hazard of COVID-19 infection was higher among male, age >50 yr and clinical role in the hospital. After adjustment for these factors, the hazard of COVID-19 infection among unvaccinated was 2.09 as compared to fully vaccinated. Vaccine effectiveness was 52.2 per cent in HCWs. INTERPRETATION & CONCLUSIONS: ChAdOx1 nCoV-19 coronavirus vaccine (Recombinant) was safe, immunogenic as well as showed effectiveness against the COVID-19 disease (CTRI/2021/01/030582).

Empagliflozin containing chitosan-alginate nanoparticles in orodispersible film: preparation, characterization, pharmacokinetic evaluation and its in-vitro anticancer activity.

OBJECTIVE: The main objective of this study was to develop the orodispersity film containing chitosan-alginate nanoparticles to improve dissolution profile, therapeutic effect with improved bioavailability of empagliflozin through oral route noninvasively for further cytotoxicity study. METHODS: The nanoparticles were developed through two-step mechanisms ionotropic pre-gelation and polyelectrolyte complexation methods. The prepared nanoparticles were added to a polymer matrix containing hypromellose, polyvinyl alcohol, and maltodextrin and cast to rapidly dissolving thin film by solvent casting method. RESULTS: The physicochemical characteristics of empagliflozin in the orodispersible film were most favorable for further studies. This formulation has achieved a higher permeability (7.2-fold) as compared to the reference drug product (Jardiance) after 45 min. In vivo pharmacokinetic studies in Wistar rats have revealed that chitosan-alginate empagliflozin nanoparticles in the orodispersible film were 1.18-fold more bioavailable in comparison to free empagliflozin in orodispersible film. The Cmax observed for the empagliflozin-loaded orodispersible film was 15.42 ± 5.13 µg/mL in comparison to 18.21 ± 5.53 µg/mL for empagliflozin nanoparticle-containing orodispersible film and 12.19 ± 6.71 µg/mL for freed rug suspension. The t1/2and AUC0-t values for chitosan-alginate nanoparticles of empagliflozin in the orodispersible film were found1.4-fold more than empagliflozin loaded orodispersible film (without nanoparticles). The cytotoxicity study has shown that chitosan-alginate nanoparticles of empagliflozin in orodispersible film achieved a 2.5-fold higher cytotoxic effect than free empagliflozin in orodispersible film in A549lung cancer cells. CONCLUSIONS: This study provides evidence that chitosan-alginate nanoparticles of empagliflozin in orodispersible film can be an effective drug carrier system to improve sustained effect with better bioavailability of poorly water-soluble drug.

In vitro characterization of tofacitinib loaded novel nanoemulgel for topical delivery for the management of rheumatic arthritis.

The purpose of the current study is to prepare the tofacitinib (TFB) nanoemulgel (NEG) for topical administration with optimized particle size, high loading efficiency, and better penetration through the skin for the treatment of rheumatic arthritis. The topical delivery of this drug avoids the hazards associated with oral delivery like upper respiratory tract infections and neutropenia. The formulations were prepared using the high-energy ultrasonication method. Oleic acid, tween 80, and propylene glycol were used to prepare TFB nanoemulsion (NE) which is then homogenized with carbopol-934 hydrogel to get the NEG loaded with TFB. The concentration of independent variables such as X1 (oil phase), X2 (surfactant), and X3 (cosurfactant) was optimized using the Box-Behnken design to check its impact on dependent variables such as Y1 (particle size) and Y2 (loading efficiency) of the NE. The minimum particle size of 106.3 ± 2.8 nm and maximum loading efficiency of 19.3 ± 1.8% were obtained for NE. The NEGs were evaluated for different organoleptic and physicochemical stability which were found within the normal range. The in vitro release studies showed 89.64 ± 0.97% cumulative release of TFB from NEG over the period of 24 h. The drug release data were fitted in different kinetic models and it followed Higuchi and Korsmeyer-Peppas model clearly showing the non-Fickian drug release from matrix system. As a result, the TFB NEG that have been produced could be a viable delivery mechanism for topical route.

Development of Biocompatible Nanoparticles of Tizanidine Hydrochloride in Orodispersible Films: In vitro Characterization, Ex vivo Permeation, and Cytotoxic Study on Carcinoma Cells.

BACKGROUND: The main limitations of the therapeutic effectiveness of tizanidine hydrochloride (TNZ) are its low bioavailability due to its tendency to undergo first-pass metabolism and short biological half-life. These factors make it an ideal candidate for formulating orally disintegrating films. OBJECTIVE: The present study was aimed to prepare nanoparticles of tizanidine hydrochloride using biodegradable polymers and loading them on orodispersible films to obtain a sustained release dissolution profile with improved permeability and further study the cytotoxicity on A549 lung carcinoma cells, MCF7 breast cancer cells, and HOP 92 non-small lung adenocarcinoma cells. METHODS: The fast-dissolving film of TNZ HCl was prepared by the solvent-casting method and characterized using scanning electron microscopy, FTIR, and XRD, and evaluated for critical quality attributes for this type of dosage form such as disintegration time, tensile strength, drug content, dissolution, and ex vivo permeability. In vitro cytotoxicity studies were also conducted on cancer cell lines to confirm the cytotoxic effect. RESULTS: The polymeric matrix containing the drug provided a rapid disintegration time varying between 7±2 and 30±2 seconds, adequate tensile strength between 1.4 and 11.25 N/mm2, and improved permeability through porcine buccal mucosa when compared to the reference product. CONCLUSION: A study of the cytotoxic effect on the MCF-7 breast cancer cells and A549 lung carcinoma cells revealed that tizanidine hydrochloride nanoparticles at 2.3 mg/film exhibited an IC50 value of 65.1 % cytotoxicity on MCF-7, approximately 100% on HOP92, and 83.5 % on A549 lung carcinoma cells, thus paving the way for a new paradigm of research for a cytotoxic study on MCF-7, HOP92, and A549 cell lines using the subject drug model prepared as oral films or biodegradable nanoparticles in oral films for site-specific targeting.

A Review on Structurally Diversified Synthesized Molecules as Monoacylglycerol Lipase Inhibitors and their Therapeutic uses.

Monoacylglycerol is a metabolic key serine hydrolase engaged in the regulation of the signalling network system of endocannabinoids, which is associated with various physiological processes like pain, inflammation, feeding cognition, and neurodegenerative diseases like Alzheimer's and Parkinson's disease. The monoacylglycerol was also found to act as a regulator and the free fatty acid provider in the proliferation of cancer cells as well as numerous aggressive tumours such as colorectal cancer, neuroblastoma, and nasopharyngeal carcinoma. It also played an important role in increasing the concentration of specific lipids derived from free fatty acids like phosphatidic acid, lysophosphatidic acid, sphingosine-1-phosphate, and prostaglandin E2. These signalling lipids are associated with cell proliferation, survival, tumour cell migration, contribution to tumour development, maturation, and metastases. In this study, we present a review on structurally diverse MAGL inhibitors, their development, and their evaluation for different pharmacological activities.