Development, optimization and characterization of cisplatin loaded cubosomes for human lung carcinoma.

OBJECTIVES: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma. SIGNIFICANCE: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time. METHODS: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization. RESULTS: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic. CONCLUSIONS: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

Cubosomes were prepared, optimized, and evaluated for cisplatin delivery.A randomized regular two level full factorial design was constructed to optimize blank cubosomes.Blank cubosomes consisted of GMO as the lipid and P407 as an emulsifying agent.In vitro release studies demonstrated sustained release of cisplatin from cubosomes at pH 7.4.Cytotoxicity assay on human lung carcinoma cell line NCI-H226 showed similar cytotoxicity between cisplatin-loaded cubosomes and pure cisplatin solution while blank cubosomes exhibited no toxicity.

Formulation and evaluation of sustained release ocular inserts of betaxolol hydrochloride using arabinoxylan from Plantago ovata.

The purpose of the current studies was to develop ocular insert of betaxolol hydrochloride (BXH), using arabinoxylan (AX) as a film former. The inserts were prepared by sandwiching I mg of BXH between two films of AX. Six different formulations of ocular inserts were prepared in such a way that first three formulations contained varying concentrations of AX along with glycerol as plasticizer, whereas, rest of the formulations were added with 0.5mg of sodium alginate, sandwiched between two films of AX along with 1mg of BXH. Chemical compatibilities of the ingredients were assessed by using FTIR. Prepared ocular inserts were subjected to various physicochemical characterizations. The dissolution studies showed that ocular inserts containing sodium alginate with the AX showed sustained release effect better than the formulations with AX alone. Addition of sodium alginate resulted in inhibition of sudden release in initial phase and further sustained the release of drug from ocular inserts. Ocular inserts were pH compatible to the eyes as well as there was no interaction among the drug and excipients, suggesting that the selected excipients were suitable for the development of sustained release ocular inserts of BXH.

Formulation of instant disintegrating buccal films without using disintegrant: An in-vitro study.

The current study was conducted to fabricate Metoclopramide HCL (MCH) and Sumatriptan succinate (SS) instant release buccal films (IRBF) without using any super disintegrant. The solvent casting method was used for the preparation of IRBFs and prepared IRBFs were physicochemically evaluated. Spectrophotometric analysis was done to determine the lambda max followed by the linearity determination of both drugs. Different concentrations such as 100, 125, and 150mg of hydrophilic polymer (HPMC E5) were employed but the concentration of glycerol was variable. Comparatively better results were observed for the formulation with 150mg of HPMC E5 and 30% glycerol. Formulated IRBFs showed good tensile strength with a mean disintegration time of 12.4-28.4 seconds and rapid dissolution with more than 50% drug release within 2 minutes. It was concluded that the chosen combination of polymers was appropriate for the fabrication of MCH and SS buccal strips.

Rosuvastatin, Perindopril and Ezetimibe loaded instant release buccal films: Development and in vitro characterization.

BACKGROUND: Rosuvastatin Calcium and Ezetimibe are used to control cholesterol level while Perindopril Erbumine is used to treat hypertension. Hepatic metabolism reduces the therapeutic effect of these drugs. OBJECTIVE: Instant release buccal films (IRBFs) could possibly be a solution to this issue. The objective of the study was to formulate IRBFs of Rosuvastatin Calcium, Perindopril Erbumine and Ezetimibe using solvent casting technique. METHODS: Polymers used to prepare IRBFs included hydroxypropyl methylcellulose (HPMC E5), PEG 400 (as plasticizer) and Tween 80 (as surfactant). Solvent casting technique was used to fabricate the films, followed by their in-vitro analysis including high performance liquid chromatography (HPLC), X-ray diffraction (XRD), fourier transform infrared evaluation (FTIR), In-vitro dissolution, In-vitro disintegration, stability tests, scanning electron microscopy (SEM), folding fortitude, thickness evaluation, surface pH, tensile strength, weight variation and percentage moisture content. RESULTS: Optical microscopy as well as SEM analysis displayed that the surfaces of IRBFs were smooth with uniform mixing of ingredients. IRBFs disintegrated within 15 seconds while on dissolution they exhibited instant drug release i.e. 100% release in 2 minutes. CONCLUSIONS: The results show promising potential of IRBFs in drug delivery.

Development of thiomer based buccal films for the enhancement of bioavailability: An in-vivo analysis.

Present work was conducted to improve the bioavailability of Tizanidine HCl (TZN) by formulating mucoadhesive buccal films (MBFs) using novel thiolated arabinoxylan (TAX) as film former. MBF's were prepared by solvent casting technique followed by their evaluation for surface morphology and folding endurance. Moreover, pharmacokinetic parameters including Cmax, tmax, t1/2 and AUC were determined after administering standard oral solution (SOS) and MBFs of TZN at a dose of 1mg/kg. Successful thiolation was confirmed by the presence of 4.98 to 7.04 mmol of thiol content per gram of the polymer. Results of in-vivo pharmacokinetics have signified (p=0.0089) the suitability of MBFs as a carrier of drug through buccal route. Results have explored that, t1/2 was increased from 2.51hrs (SOS) to 10 hrs, Cmax from 42.3 ng/ml (SOS) to 105ng/ml and tmax from 2hrs (SOS) to 6h. Conclusively, TAX has exhibited the potential to form MBFs thereby offering sustained release of TZN with improved pharmacokinetic profile.

Development and optimization of flurbiprofen loaded microsponges; an in-vitro evaluation.

Current study was designed with the aim to employ quasi emulsification, and double emulsification techniques for the development of Flurbiprofen (FLB) loaded micro sponges, followed by their physicochemical evaluation. FTIR interpretations exhibited compatibility of ingredients, while crystallographic analysis revealed crystalline nature of pure drug, which was masked upon incorporation into microsponges. Optical microscope and SEM have exposed spherical and spongy surfaces of prepared micro sponges. Micromeritics suggested that the flow properties are excellent and microsponges have remarkable drug entrapment efficiency (98.55±0.08%). In-vitro dissolution studies demonstrated good control over release of FLB until 8th h from the prepared microsponges. However, a difference in cumulated amount of released drug was noticed i.e. EC based formulation has released about 99.3±0.10%, while XG facilitated EC based formulations offered 92.7±2.1% release of the drug. Zeta potential indicated access of negative charge while zeta sizer has described the range of the particle size between 2.6 to 3.5µm. Conclusively the results have advocated the suitability of selected ingredients for incorporation of FLB into microsponges for its sustained delivery.

Antibiotic resistance pattern shown by various pathogens, causing infections in neonates.

This study was schemed to comprehend the latest kaleidoscopic trends of bacterial resistance in neonatal pathogens against all those antibiotics commonly employed as empirical therapy in neonates. The methodological approach included; isolation and subsequent identification of those pathogens having caused bacterial infections in neonates, application of antibiotic sensitivity testing and finally construing the conclusion depicting patterns of antibiotic resistance by various pathogens, isolated from neonatal biological samples. Antibiotic resistance patterns was evident in gram-positive as well as in gram-negative bacteria in all the eight species identified in this study. Even antibiotic drugs which are being commonly relied upon for treating multi-resistant bacterial infections, found to be in effective against many newly emerged resistant bacteria, when used alone. Resistance Antibiotics drugs against which most prominent resistance pattern emerged include; Amikacin sulphate, Linezolid, Piperacillin / Tazobactam, Amoxicillin / Clavulanic acid, Vencomycin, Cefoperazone / Sulbactam, Ceftriaxone sodium, Ciprofloxacin, Cefixime trihydrate and Imipenem. The inferred upshot suggests that antibiotic resistance is emerging fast and ever-changing phenomenon of antibiotic resistance has significantly reduced the therapeutic space to maneuver, particularly, in treating neonatal infections.

Biological evaluation of synthetic α,ß-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-ß aggregation.

A series of new α,ß-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aß1-42 aggregation. The effect of these compounds against amyloid ß-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aß1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037µM) inhibitory potential. Furthermore, compound 3o disassembled the Aß fibrils produced by self-induced Aß aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aß aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aß-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.

In Vivo Antitumor Activity of Folate-Conjugated Cholic Acid-Polyethylenimine Micelles for the Codelivery of Doxorubicin and siRNA to Colorectal Adenocarcinomas.

Multidrug resistance poses a great challenge to cancer treatment. In order to improve the targeting and codelivery of small interfering RNA (siRNA) and doxorubicin, and to overcome multidrug resistance, we conjugated a cholic acid-polyethylenimine polymer with folic acid, forming CA-PEI-FA micelles. CA-PEI-FA exhibited a low critical micelle concentration (80 µM), small average particle size (150 nm), and positive zeta potential (+ 12 mV). They showed high entrapment efficiency for doxorubicin (61.2 ± 1.7%, w/w), forming D-CA-PEI-FA, and for siRNA, forming D-CA-PEI-FA-S. X-ray photoelectron spectroscopic analysis revealed the presence of external FA on D-CA-PEI-FA micelles. About 25% doxorubicin was released within 24 h at pH 7.4, while more than 30% release was observed at pH 5. The presence of FA enhanced micelle antitumor activity. The D-CA-PEI-FA and D-CA-PEI-FA-S micelles inhibited tumor growth in vivo. No significant differences between their in vitro cytotoxic activities or their in vivo antitumor effects were observed, indicating that the siRNA coloading did not significantly increase the antitumor activity. Histological analysis revealed that tumor tissues from mice treated with D-CA-PEI-FA or D-CA-PEI-FA-S showed the lowest cancer cell density and the highest levels of apoptosis and necrosis. Similarly, the livers of these mice exhibited the lowest level of dihydropyrimidine dehydrogenase among all treated groups. The lowest serum vascular endothelial growth factor level (VEGF) (24.4 pg/mL) was observed in mice treated with D-CA-PEI-FA-S micelles using siRNA targeting VEGF. These findings indicated that the developed CA-PEI-FA nanoconjugate has the potential to achieve targeted codelivery of drugs and siRNA.

Pharmacological evaluation and docking studies of α,ß-unsaturated carbonyl based synthetic compounds as inhibitors of secretory phospholipase A2, cyclooxygenases, lipoxygenase and proinflammatory cytokines.

Arachidonic acid and its metabolites have generated high level of interest among researchers due to their vital role in inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as synergistic anti-inflammatory effect. A series of novel α,ß-unsaturated carbonyl based compounds were synthesized and evaluated for their inhibitory activity on secretory phospholipase A2 (sPLA2), cyclooxygenases (COX), soybean lipoxygenase (LOX) in addition to proinflammatory cytokines comprising IL-6 and TNF-α. Six α,ß-unsaturated carbonyl based compounds (2, 3, 4, 12, 13 and 14) exhibited strong inhibition of sPLA2 activity, with IC50 values in the range of 2.19-8.76 µM. Nine compounds 1-4 and 10-14 displayed inhibition of COX-1 with IC50 values ranging from 0.37 to 1.77 µM (lower than that of reference compound), whereas compounds 2, 10, 13 and 14 strongly inhibited the COX-2. The compounds 10-14 exhibited strong inhibitory activity against LOX enzyme. All compounds were evaluated for the inhibitory activities against LPS-induced TNF-α and IL-6 release in the macrophages. On the basis of screening results, five active compounds 3, 4, 12, 13 and 14 were found strong inhibitors of TNF-α and IL-6 release in a dose-dependent manner. Molecular docking experiments were performed to clarify the molecular aspects of the observed COX and LOX inhibitory activities of the investigated compounds. Present findings increases the possibility that these α,ß-unsaturated carbonyl based compounds might serve as beneficial starting point for the design and development of improved anti-inflammatory agents.

Platinum-based targeted chemotherapies and reversal of cisplatin resistance in non-small cell lung cancer (NSCLC).

Lung cancer is the one of the most prevalent cancer in the world. It kills more people from cancer than any other cause and is especially common in underdeveloped nations. With 1.2 million instances, it is also the most prevalent cancer in men worldwide, making about 16.7% of the total cancer burden. Surgery is the main form of curative treatment for early-stage lung cancer. However, the majority of patients had incurable advanced non-small cell lung cancer (NSCLC) recurrence after curative purpose surgery, which is indicative of the aggressiveness of the illness and the dismal outlook. The gold standard of treatment for NSCLC patients includes drug targeting of specific mutated genes drive in development of lung cancer. Furthermore, patients with advanced NSCLC and those with early-stage illness needing adjuvant therapy should use cisplatin as it is the more active platinum drug. So, this review encompasses the non-small cell lung cancer microenvironment, treatment approaches, and use of cisplatin as a first-line regimen for NSCLC, its mechanism of action, cisplatin resistance in NSCLC and also the prevention strategies to revert the drug resistance.

Nanoparticles incorporated hydrogels for delivery of antimicrobial agents: developments and trends.

The prevention and treatment of microbial infections is an imminent global public health concern due to the poor antimicrobial performance of the existing antimicrobial regime and rapidly emerging antibiotic resistance in pathogenic microbes. In order to overcome these problems and effectively control bacterial infections, various new treatment modalities have been identified. To attempt this, various micro- and macro-molecular antimicrobial agents that function by microbial membrane disruption have been developed with improved antimicrobial activity and lesser resistance. Antimicrobial nanoparticle-hydrogels systems comprising antimicrobial agents (antibiotics, biological extracts, and antimicrobial peptides) loaded nanoparticles or antimicrobial nanoparticles (metal or metal oxide) constitute an important class of biomaterials for the prevention and treatment of infections. Hydrogels that incorporate nanoparticles can offer an effective strategy for delivering antimicrobial agents (or nanoparticles) in a controlled, sustained, and targeted manner. In this review, we have described an overview of recent advancements in nanoparticle-hydrogel hybrid systems for antimicrobial agent delivery. Firstly, we have provided an overview of the nanoparticle hydrogel system and discussed various advantages of these systems in biomedical and pharmaceutical applications. Thereafter, different hybrid hydrogel systems encapsulating antibacterial metal/metal oxide nanoparticles, polymeric nanoparticles, antibiotics, biological extracts, and antimicrobial peptides for controlling infections have been reviewed in detail. Finally, the challenges and future prospects of nanoparticle-hydrogel systems have been discussed.

Fibrin-targeted phase shift microbubbles for the treatment of microvascular obstruction.

Rationale: Microvascular obstruction (MVO) following percutaneous coronary intervention (PCI) is a common problem associated with adverse clinical outcomes. We are developing a novel treatment, termed sonoreperfusion (SRP), to restore microvascular patency. This entails using ultrasound-targeted microbubble cavitation (UTMC) of intravenously administered gas-filled lipid microbubbles (MBs) to dissolve obstructive microthrombi in the microvasculature. In our prior work, we used standard-sized lipid MBs. In the present study, to improve upon the efficiency and efficacy of SRP, we sought to determine the therapeutic efficacy of fibrin-targeted phase shift microbubbles (FTPSMBs) in achieving successful reperfusion of MVO. We hypothesized that owing to their much smaller size and affinity for thrombus, FTPSMBs would provide more effective dissolution of microthrombi when compared to that of the corresponding standard-sized lipid MBs. Methods: MVO in the rat hindlimb was created by direct injection of microthrombi into the left femoral artery. Definity MBs (Lantheus Medical Imaging) were infused through the jugular vein for contrast-enhanced ultrasound imaging (CEUS). A transducer was positioned vertically above the hindlimb for therapeutic US delivery during the concomitant administration of various therapeutic formulations, including (1) un-targeted MBs; (2) un-targeted phase shift microbubbles (PSMBs); (3) fibrin-targeted MB (FTMBs); and (4) fibrin-targeted PSMBs (FTPSMBs). CEUS cine loops with burst replenishment were obtained at baseline (BL), 10 min post-MVO, and after each of two successive 10-minute SRP treatment sessions (TX1, TX2) and analyzed (MATLAB). Results: In-vitro binding affinity assay showed increased fibrin binding peptide (FBP) affinity for the fibrin clots compared with the untargeted peptide (DK12). Similarly, in our in-vitro model of MVO, we observed a higher binding affinity of fluorescently labeled FTPSMBs with the porcine microthrombi compared to FTMBs, PSMBs, and MBs. Finally, in our hindlimb model, we found that UTMC with FTPSMBs yielded the greatest recovery of blood volume (dB) and flow rate (dB/sec) following MVO, compared to all other treatment groups. Conclusions: SRP with FTPSMBs achieves more rapid and complete reperfusion of MVO compared to FTMBs, PSMBs, and MBs. Studies to explore the underlying physical and molecular mechanisms are underway.

Discovery of Novel Tetramethylpyrazine Containing Chalcone Derivatives as Anti-Inflammatory Agents.

BACKGROUND: Chalcones are precursors of flavonoids and exhibit a broad spectrum of pharmacological activity. OBJECTIVE: As anti-inflammatory agents, two series of chalcone derivatives and chalcone-based oximes were synthesized and characterized. To integrate the tetramethylpyrazine moiety into these novel molecules, the multifunctional natural chemical ligustrazine was employed. METHODS: A variety of newly synthesized ligustrazine-based chalcones were utilized as precursors for the synthesis of new oximes and their inhibitory activity against COX-1, COX-2, and LOX-5 enzymes were compared. RESULTS: The conversion of ketones to their oxime derivatives increased the effectiveness of COX-1 and COX-2 inhibition. Due to the substituted ether groups, oxime derivative 5d had the lowest IC50 values of 0.027 ± 0.004 µM and 0.150 ± 0.027 µM for COX-1 and COX-2 isoenzymes, respectively. Notably, the oxime derivative's highest effectiveness is conferred by the presence of methoxymethoxy or hydroxy groups at the C-3 and C-4 positions on the phenyl ring. The 6b derivative with a long alkyl chain ether group was shown to be the most powerful 5-LOX inhibitor. All compounds were also assessed for their ability to inhibit nitric oxide generation and LPS-induced IL-6, IL-1ß, and TNF-α production in RAW 264.7 macrophages. Finally, in order to determine the structural effects responsible for the binding mechanism of compounds, they were docked into the binding sites of COX-1, COX-2, and 5-LOX, which revealed an inhibitory mechanism of action and demonstrated the relevance of various types of interactions. CONCLUSION: The findings showed that these novel compounds had a significant impact on antiinflammatory actions.

Thiolated Polymeric Hydrogels for Biomedical Applications: A Review.

Hydrogels are a three-dimensional (3D) network of hydrophilic polymers. The physical and chemical crosslinking of polymeric chains maintains the structure of the hydrogels even when they are swollen in water. They can be modified with thiol by thiol epoxy, thiol-ene, thiol-disulfide, or thiol-one reactions. Their application as a matrix for protein and drug delivery, cellular immobilization, regenerative medicine, and scaffolds for tissue engineering was initiated in the early 21st century. This review focuses on the ingredients, classification techniques, and applications of hydrogels, types of thiolation by different thiol-reducing agents, along with their mechanisms. In this study, different applications for polymers used in thiolated hydrogels, including dextran, gelatin, polyethylene glycol (PEG), cyclodextrins, chitosan, hyaluronic acid, alginate, poloxamer, polygalacturonic acid, pectin, carrageenan gum, arabinoxylan, carboxymethyl cellulose (CMC), gellan gum, and polyvinyl alcohol (PVA) are reviewed.

Covalent Organic Frameworks (COFs) as Multi-Target Multifunctional Frameworks.

Covalent organic frameworks (COFs), synthesized from organic monomers, are porous crystalline polymers. Monomers get attached through strong covalent bonds to form 2D and 3D structures. The adjustable pore size, high stability (chemical and thermal), and metal-free nature of COFs make their applications wider. This review article briefly elaborates the synthesis, types, and applications (catalysis, environmental Remediation, sensors) of COFs. Furthermore, the applications of COFs as biomaterials are comprehensively discussed. There are several reported COFs having good results in anti-cancer and anti-bacterial treatments. At the end, some newly reported COFs having anti-viral and wound healing properties are also discussed.

Effect of Ultrasound Pulse Length on Sonoreperfusion Therapy.

In recent years, long- and short-pulse ultrasound (US)-targeted microbubble cavitation (UTMC) has been found to increase perfusion in healthy and ischemic skeletal muscle, in pre-clinical animal models of microvascular obstruction and in the myocardium of patients presenting with acute myocardial infarction. There is evidence that the observed microvascular vasodilation is driven by the nitric oxide pathway and purinergic signaling, but the time course of the response and the dependency on US pulse length are not well elucidated. Because our prior data supported that sonoreperfusion efficacy is enhanced by long-pulse US versus short-pulse US, in this study, we sought to compare long-pulse (5000 cycles) and short-pulse (500 × 10 cycles) US at a pressure of 1.5 MPa with an equivalent total number of acoustical cycles, hence constant acoustic energy, and at the same frequency (1 MHz), in a rodent hind limb model with and without microvascular obstruction (MVO). In quantifying perfusion using burst replenishment contrast-enhanced US imaging, we made three findings: (i) Long and short pulses result in different vasodilation kinetics in an intact hind limb model. The long pulse causes an initial spasmic reduction in flow that spontaneously resolved at 4 min, followed by sustained higher flow rates (approximately twofold) compared with baseline, starting 10 min after therapy (p < 0.05). The short pulse caused a short-lived approximately twofold increase in flow rate that peaked at 4 min (p < 0.05), but without the initial spasm. (ii) The sustained increased response with the long pulse is not simply reactive hyperemia. (iii) Both pulses are effective in reperfusion of MVO in our hindlimb model by restoring blood volume, but only the long pulse caused an increase in flow rate after treatment ii, compared with MVO (p < 0.05). Histological analysis of hind limb muscle post-UTMC with either pulse configuration indicates no evidence of tissue damage or hemorrhage. Our findings indicate that the microbubble oscillation induces vasodilation, and therapeutic efficacy for the treatment of MVO can be tuned by varying pulse length; relative to short-pulse US, longer pulses drive greater microbubble cavitation and more rapid microvascular flow rate restoration after MVO, warranting further optimization of the pulse length for sonoreperfusion therapy.

Synthesis, Characterization, and Biological Evaluation of Meldrum's Acid Derivatives: Dual Activity and Molecular Docking Study.

In the presented study, eight novel Meldrum's acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum's acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 µM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 µM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best Eb was noted for the topoisomerase II beta-LYS482-3i cluster.

An Insight into the Role of Artificial Intelligence in the Early Diagnosis of Alzheimer's Disease.

BACKGROUND: The complication of Alzheimer's disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the major hurdle behind its treatment. Several studies have aimed to identify potential biomarkers that can be detected in body fluids (CSF, blood, urine, etc.) or assessed by neuroimaging (i.e., PET and MRI). However, the clinical implementation of these biomarkers is incomplete as they cannot be validated. METHODS: This study aimed to overcome the limitation of using artificial intelligence along with technical tools that have been extensively investigated for AD diagnosis. For developing a promising artificial intelligence strategy that can diagnose AD early, it is critical to supervise neuropsychological outcomes and imaging-based readouts with a proper clinical review. CONCLUSION: Profound knowledge, a large data pool, and detailed investigations are required for the successful implementation of this tool. This review will enlighten various aspects of early diagnosis of AD using artificial intelligence.

Synthesis of Thiol-Modified Hemicellulose, Its Biocompatibility, Studies, and Appraisal as a Sustained Release Carrier of Ticagrelor.

Background: Nature has always been considered as the primary source of pharmaceutical ingredients. A variety of hemicelluloses, as well as their modified forms, have been under investigation. Herein, a study was designed to explore the biocompatibility of hemicellulose and its modified form (thiolated hemicellulose) as well as its potential as a pharmaceutical excipient. Method: For thiol modification thiourea was used as the thiol donor, HCl as the catalytic reagent, and methanol was used for washing purposes. Modified polymers were characterized for physicochemical characteristics, including surface morphology, the amorphous or crystalline nature of the particles, modification of polymer by FTIR, and biocompatibilities. For acute oral toxicity study, a single dose of 2 g/kg was administered to albino rats of 200 g average weight (n = 3). Polymers were evaluated as pharmaceutical excipients by preparing compressed tablets of antiplatelet drug (Ticagrelor), followed by various quality control tests, such as swelling index, thickness and diameter, disintegration, and in-vitro drug release. Results: From the results, it was observed that thiol modification has been successfully accomplished as characteristic peaks belonging to -SH group appeared at 2667.7691 cm-1 in FTIR scan. The modified polymer was found safe in the use concentration range, confirming their safe use for in vivo analysis. No significant effect has been observed in the behavior, biological fluid (blood), or on vital organs. Thiolated hemicellulose was found to be an excellent drug retarding polymer as 8 h of dissolution studies showed that 67.08% of the drug has been released. Conclusion: Conclusively, incorporation of thiol moiety made the polymer more mucoadhesive with, and a worthy carrier of, the drug with good biocompatibilities.