Alkanols Regulate the Fluidity of Phospholipid Bilayer in Accordance to Their Concentration and Polarity.

In spite of the widespread use of alkanols as penetration enhancers, their effect on vesicular formulations remains largely unexplored. These can affect the stability and integrity of the phospholipid bilayers. In this study, we have investigated the interaction of linear (ethanol, butanol, hexanol, octanol) and branched alkanols (t-amylol and t-butanol) with three phospholipids (soya lecithin, SL; soy L-α-phosphatidylcholine, SPC; and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC). Thermodynamic and structural aspects of these interactions were studied as a function of the alkanol concentration and chain length. Our interpretations are based on isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) experiments. We observed one-site interactions wherein hydroxyl and acyl groups interacted with the polar and nonpolar regions of the phospholipid, respectively. The stability and structural integrity of bilayers appeared to be dependent upon (a) the hydrocarbon chain length and concentration of alcohols, and (b) the degree of unsaturation in the phospholipid molecule. We found that these interactions triggered a reduction in the enthalpy which was compensated by increased entropy, keeping free energy negative. Drop in enthalpy indicates reversible disordering of the bilayer which enables the diffusion of alcohol without triggering destabilization. Ethanol engaged predominantly with the interface, and it resulted in higher enthalpic changes. Interactions became increasingly unfavorable with longer alcohols - a cutoff point was recorded with hexanol. The overall sequence of membrane disordering capability was recorded as follows: ethanol < butanol < octanol < hexanol. Octanol's larger size restricted its penetration in the bilayer, and hence it caused less enthalpic changes relative to hexanol. This could also be verified from the trends in the area ratio of these vesicles obtained from the DLS data. Branched alkanols displayed a lower binding affinity with the phospholipids relative to their linear counterparts. These data are useful while contemplating the inclusion of short-chain alcohols as penetration enhancers in phospholipid vesicles.

A nonionic microemulsion co-loaded with atorvastatin and quercetin: Simultaneous spectroscopic analysis and payload release kinetics.

In this study, we have co-loadedatorvastatin (ATR) and quercetin (QCT) in a nonionic microemulsion. After developing a derivative ratio spectrophotometric technique for simultaneous analysis of ATR and QCT, pseudoternary phase diagram was constructed utilizing1:4 d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and ethanol as surfactant and cosurfactant, respectively. Oleic acid was used as oil phase. Structural characterization of the formulation was carried out along a water dilution line created in monophasic region. Characterizations at these dilution points were performed using dynamic light scattering and polarized light microscopy. The average hydrodynamic size of the optimized formulation was found to be 18.9 nm and it did not change upon loading of ATR and QCT. In vitro release was assessed for the formulations loaded with different ratios of ATR and QCT, and the data were fitted to different mathematical models. Interestingly, we noticed differences in release kinetics during changes in dose ratios, particularly for QCT. Higuchi kinetics, observed at equal dose, shifted to Korsmeyer-Peppas model at higher QCT-ATR ratio (2:1 and 4:1). This difference is attributable to the ability of QCT molecules of overwhelming the interface at higher concentrations. Altogether, our observations highlight that the ratio of payloads should be selected carefully in order to avoid unpredictable release patterns.

Sugar-based Cryoprotectants Stabilize Liposomal Vesicles by Exhibiting a Cholesterol-like Effect.

Liposomal vesicles tend to fuse and aggregate during lyophilization. To avoid these events, cryoprotectants are added to the dispersion before lyophilization. Herein, we have compared the effect of three commonly used cryoprotectants (mannitol, MTL; trehalose, THL; and ß-cyclodextrin, ß-CD) upon structural characteristics of liposomes. The formulation was prepared using ethanol injection method, and cryoprotectants were tested at three dose levels (2, 6, and 10 mM). We have elucidated their effect on soy lecithin (SL) liposomes formulated with and without cholesterol (CHL). Characterizations were performed using scattering, thermal, and spectroscopic techniques. CHL molecules interacted hydrophobically with the SL bilayer. In spite of triggering a noticeable increase in the hydrodynamic diameter (about 30 nm), CHL promoted the stabilization of vesicles. Hydrogen bonding interactions were verified by the shift in -OH stretching over 3300-3500 cm-1. This manifested in an increased phase transition temperature (Tm) of SL liposomes. Tm increased further upon incorporation of cryoprotectants, particularly with ß-CD. Enthalpic changes were indicative of an affinity interaction between phospholipids and cryoprotectants, regardless of the presence of CHL. ß-CD showed concentration-dependent changes in the energetics of this interaction. The affinity of cryoprotectant-liposome interaction has been ranked as ß-CD ≫ THL > MNT.

Effect of stoichiometry upon the characteristics of quercetin-arginine cocrystals formulated through solution crystallization.

OBJECTIVE: The aim of this study is to demonstrate the effect of stoichiometry upon characteristics of quercetin-arginine (QCT-Arg) cocrystals. SIGNIFICANCE: Quercetin (QCT) is a most abundant flavonoid in vegetables and fruits and has been widely used as an antioxidant. However, its oral bioavailability remains low due to poor aqueous solubility. We illustrate that QCT-Arg cocrystals formulated through an optimized stoichiometry can be a useful approach for its solubilization. METHOD: Cocrystals were prepared using solvent evaporation method. Characterizations were performed through microscopic, spectroscopic, and thermal techniques. The stoichiometry was confirmed from the binary phase diagram which was prepared using thermograms derived from differential scanning calorimetric experiments. RESULT: Cocrystal formation was accompanied by the conversion of isotropic phase into anisotropic one. Thread-like cocrystals were formed, regardless of QCT-Arg stoichiometry and solvent's polarity. Spectral analyses suggested that cocrystal structure was held together by hydrogen bonding between QCT and Arg. We ruled out the existence of eutectic mixture based on the observation of two eutectic points in the binary phase diagram. CONCLUSION: Morphology of cocrystals remained unaffected by the solvent type, stoichiometry and the presence of surfactant. We noticed that the cocrystals could improve the aqueous solubility of QCT.

Localized Delivery of Bioactives using Structured Liposomal Gels.

Liposomes have gained a lot of interest for drug delivery applications, and some of these preparations have been commercialized. These are formulated with biocompatible components and can be used for delivering a wide range of payloads differing in aqueous solubility and molecular weight. Liposome-based delivery approaches are limited mainly by two factors: (a) poor dispersion stability, and (b) pre-mature leakage of payloads. In this review, we have discussed the stabilization of liposomal vesicles by their entrapment in hydrogels. Studies reveal that such hydrogels can maintain the structural integrity of liposomes. Release of liposomes from the hydrogel network can be modulated through careful screening of matrix former and degree of its cross-linking. Accordingly, we have reviewed the approaches of stabilizing liposomal vesicles through entrapment in hydrogels. Application of liposome-embedded hydrogels has been reviewed in context of localized drug delivery. Our discussion is focussed on the delivery of bioactives to the skin. Such an approach appears alluring from the standpoint of minimizing the undesirable distribution of payload(s) the systemic circulation and off-target sites.

Analytical sameness methodology for the evaluation of structural, physicochemical, and biological characteristics of Armlupeg: A pegfilgrastim biosimilar case study.

Pegfilgrastim is administered as an adjunct to chemotherapy to reduce the incidence of febrile neutropenia and associated infectious complications. Lupin's Pegfilgrastim is a proposed biosimilar to the U.S.-referenced Neulasta®. Demonstration of biosimilarity requires extensive physicochemical and functional characterization of the biosimilar, and demonstration of analytical similarity to the reference product, in addition to clinical studies. This work is a case study for demonstrating the analytical similarity of Armlupeg (Lupin's Pegfilgrastim) to Neulasta® with respect to structural and physicochemical attributes using several robust, orthogonal, and state-of-the-art techniques including high-end liquid chromatography, mass spectrometry, and spectroscopy techniques; circular dichroism; differential scanning calorimetry; nuclear magnetic resonance; analytical ultracentrifugation; and micro-flow imaging. Functional similarity was demonstrated using an in vitro cell proliferation assay to measure relative potency and surface plasmon resonance to measure receptor binding kinetics. Furthermore, comparative forced-degradation studies were performed to study the degradation of the products under stress conditions. The product attributes were ranked based on a critical quality attributes risk score according to their potential clinical impact. Based on criticality, all analyses were statistically evaluated to conclude analytical similarity. Lupin's Pegfilgrastim was comparable to Neulasta® as demonstrated via structural, functional, and purity analyses. Lupin's Pegfilgrastim complied with the quality and statistical ranges established using Neulasta®. Both products follow the same degradation pathways under stress conditions as observed in the forced-degradation studies. No new impurity or degradation product was observed in Lupin's Pegfilgrastim. These data conclusively demonstrate the analytical similarity of Lupin's Pegfilgrastim and Neulasta®.

Comparative Effect of Physiological Salts upon Micellization of T1304 and T1307.

We present a comprehensive investigation on the interaction of tetronics (T1304 and T1307) with some important physiological salts (NaH2PO4, KH2PO4, Na2CO3, NaCl, and KI). Thermodynamic and microstructural aspects of these interactions were studied as a function of the solution temperature, pH and salt concentration. Characterizations were performed using turbidimetric, calorimetric, and scattering techniques. We show that, at ambient temperature, T1304 molecules aggregated to form spherical core-shell aggregates displaying a unimodal distribution pattern. On the other hand, unimers and large clusters dominated in the case of highly hydrophilic T1307. Its micellization was promoted in the presence of salts as per the following trend: NaCl < KH2PO4 < NaH2PO4 ≪ Na2CO3. Aggregation was found to be endothermic, and hydrophobic interactions (TΔSmic > ΔHmic) prevailed. The enthalpy-entropy compensation plot was found to be linear for both copolymers. Demicellization occurred in the presence of KI as it facilitated the buildup of water structures around the copolymer chains. This could be verified from the increase in the cloud point, critical micelle concentration, and free energy. Overall, the temperature and salts inflicted a stronger hydrophobic effect upon T1304 in comparison to T1307.

Structural Changes in Liposomal Vesicles in Association with Sodium Taurodeoxycholate.

Liposomes composed of soy lecithin (SL) have been studied widely for drug delivery applications. The stability and elasticity of liposomal vesicles are improved by incorporating additives, including edge activators. In this study, we report the effect of sodium taurodeoxycholate (STDC, a bile salt) upon the microstructural characteristics of SL vesicles. Liposomes, prepared by the thin film hydration method, were characterized by dynamic light scattering (DLS), small-angle neutron scattering (SANS), electron microscopy, and rheological techniques. We noticed a reduction in the size of vesicles with the incremental addition of STDC. Initial changes in the size of spherical vesicles were ascribed to the edge-activating action of STDC (0.05 to 0.17 µM). At higher concentrations (0.23 to 0.27 µM), these vesicles transformed into cylindrical structures. Morphological transitions at higher STDC concentrations would have occurred due to its hydrophobic interaction with SL molecules in the bilayer. This was ascertained from nuclear magnetic resonance observations. Whereas shape transitions underscored the deformability of vesicles in the presence of STDC, the consistency of bilayer thickness ruled out any dissociative effect. It was interesting to notice that SL-STDC mixed structures could survive high thermal stress, electrolyte addition, and dilution.

Stabilization of lysozyme in aqueous dispersion of graphene oxide sheets.

This study examines the effect of surface oxygen groups upon ability of graphene oxide (GO) sheets in suppressing the fibrillation of lysozyme (LYZ). Graphite was oxidized using 6 and 8 wt equivalents of KMnO4, and as produced sheets were abbreviated as GO-06 and GO-08, respectively. Particulate characteristics of sheets were characterized by light scattering and electron microscopic techniques, and their interaction with LYZ was analysed by circular dichroism (CD) spectroscopy. After ascertaining acid-driven conversion of LYZ to fibrillary form, we have shown that the fibrillation of dispersed protein can be prevented by adding GO sheets. Inhibitory effect could be attributed to binding of LYZ over the sheets via noncovalent forces. A comparison between GO-06 and GO-08 samples showed superior binding affinity of the latter. Higher aqueous dispersibility and density of oxygenated groups in GO-08 sheets would have facilitated the adsorption of protein molecules, thus making them unavailable for aggregation. Pre-treatment of GO sheets with Pluronic 103 (P103, a nonionic triblock copolymer), caused reduction in the adsorption of LYZ. P103 aggregates would have rendered the sheet surface unavailable for the adsorption of LYZ. Based on these observations, we conclude that fibrillation of LYZ can be prevented in association with graphene oxide sheets.

Assessment of copper (Cu) nanoparticle for their biocontrol activity against Xanthomonas oryzae pv. oryzae, growth promotion, and physiology of rice (Oryza sativa L.) plants.

Among the various biotic factors that disrupt crop yield, Xanthomonas oryzae pv oryzae (Xoo) is the most ruinous microbe of rice and causes bacterial leaf blight (BLB) disease. The present study focused on the utilization of copper nanoparticles (Cu-NPs) to control BLB. The copper nanosuspension (259.7 nm) prepared using Na-CMC, CuSO4·7H2O, and NaOH showed effectively inhibited Xoo (65.0 µg/ml). The performance of Cu-NPs in vivo showed enhanced plant attributes (127.9% root length and 53.9% shoot length) compared to the control and CuSO4 treated seedling. Furthermore, Cu-NPs treated seedlings showed 23.01% disease incidence (DI) compared to CuSO4 (85.71%) treated and control plants (91.83%). In addition to enhancing the growth parameters and reducing DI, seed priming with Cu-NPs improved the total chlorophyll content to 36.0% compared to the control. The assessment of antioxidant enzymes such as superoxide dismutase (1.9 U), polyphenol oxidase, peroxidase, and phenylalanine ammonia-lyase (two- to three-fold) in roots and shoots of rice plants revealed significant enhancement in Cu-NPs treated seedlings (P < 0.05). The present study suggests that Cu-NPs can be used to control Xoo and enhance rice growth.

Detection and modulation of neurodegenerative processes using graphene-based nanomaterials: Nanoarchitectonics and applications.

Neurodegenerative disorders (NDDs) are caused by progressive loss of functional neurons following the aggregation and fibrillation of proteins in the central nervous system. The incidence rate continues to rise alarmingly worldwide, particularly in aged population, and the success of treatment remains limited to symptomatic relief. Graphene nanomaterials (GNs) have attracted immense interest on the account of their unique physicochemical and optoelectronic properties. The research over the past two decades has recognized their ability to interact with aggregation-prone neuronal proteins, regulate autophagy and modulate the electrophysiology of neuronal cells. Graphene can prevent the formation of higher order protein aggregates and facilitate the clearance of such deposits. In this review, after highlighting the role of protein fibrillation in neurodegeneration, we have discussed how GN-protein interactions can be exploited for preventing neurodegeneration. A comprehensive understanding of such interactions would contribute to the exploration of novel modalities for controlling neurodegenerative processes.

Implications of regulatory T cells in anti-cancer immunity: from pathogenesis to therapeutics.

Regulatory T cells (Tregs) play an essential role in maintaining immune tolerance and suppressing inflammation. However, Tregs present major hurdle in eliciting potent anti-cancer immune responses. Therefore, curbing the activity of Tregs represents a novel and efficient way towards successful immunotherapy of cancer. Moreover, there is an emerging interest in harnessing Treg-based strategies for augmenting anti-cancer immunity in different types of the disease. This review summarises the crucial mechanisms of Tregs' mediated suppression of anti-cancer immunity and strategies to suppress or to alter such Tregs to improve the immune response against tumors. Highlighting important clinical studies, the review also describes current Treg-based therapeutic interventions in cancer, and discusses Treg-suppression by molecular targeting, which may emerge as an effective cancer immunotherapy and as an alternative to detrimental chemotherapeutic agents.

Advances on nanoformulation approaches for delivering plant-derived antioxidants: A case of quercetin.

Oxidative stress has been implicated in tumorigenic, cardiovascular, neuro-, and age-related degenerative changes. Antioxidants minimize the oxidative damage through neutralization of reactive oxygen species (ROS) and other causative agents. Ever since the emergence of COVID-19, plant-derived antioxidants have received enormous attention, particularly in the Indian subcontinent. Quercetin (QCT), a bio-flavonoid, exists in the glycosylated form in fruits, berries and vegetables. The antioxidant potential of QCT analogs relates to the number of free hydroxyl groups in their structure. Despite presence of these groups, QCT exhibits substantial hydrophobicity. Formulation scientists have tested nanotechnology-based approaches for its improved solubilization and delivery to the intended site of action. By the virtue of its hydrophobicity, QCT gets encapsulated in nanocarriers carrying hydrophobic domains. Apart from passive accumulation, active uptake of such formulations into the target cells can be facilitated through well-studied functionalization strategies. In this review, we have discussed the approaches of improving solubilization and bioavailability of QCT with the use of nanoformulations.

Graphene quantum dots: A review on the effect of synthesis parameters and theranostic applications.

The rising demand for early-stage diagnosis of diseases such as cancer, diabetes, neurodegenerative can be met with the development of materials offering high sensitivity and specificity. Graphene quantum dots (GQDs) have been investigated extensively for theranostic applications owing to their superior photostability and high aqueous dispersibility. These are attractive for a range of biomedical applications as their physicochemical and optoelectronic properties can be tuned precisely. However, many aspects of these properties remain to be explored. In the present review, we have discussed the effect of synthetic parameters upon their physicochemical characteristics relevant to bioimaging. We have highlighted the effect of particle properties upon sensing of biological molecules through 'turn-on' and 'turn-off' fluorescence and generation of electrochemical signals. After describing the effect of surface chemistry and solution pH on optical properties, an inclusive view on application of GQDs in drug delivery and radiation therapy has been given. Finally, a brief overview on their application in gene therapy has also been included.

Formulation development of tocopherol polyethylene glycol nanoengineered polyamidoamine dendrimer for neuroprotection and treatment of Alzheimer disease.

Amyloid-beta (Aß) aggregates deposition at extra neuronal sites induces neurotoxicity and major hallmarks of Alzheimer's disease (AD). To reduce the Aß fibril toxicity, multi-functional polyamidoamine (PAMAM) dendrimer was conjugated with tocopheryl polyethylene glycol succinate-1000 (TPGS) which acts as a carrier matrix for the delivery of neuroprotective molecule piperine (PIP). This PIP-TPGS-PAMAM dendrimer was fabricated to mitigate the Aß1-42 fibril toxicity on SHSY5Y cells. TPGS-PAMAM was fabricated through carbodiimide coupling reaction, and PIP was encapsulated in dendrimer through solvent injection method to prepare PIP-TPGS-PAMAM. Antioxidant assay of PIP-TPGS-PAMAM showed 90.18% inhibition of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radicals compared to free PIP, which was 28.27%. The SHSY5Y cells showed 37.25% for negative control group and 82.55% cell viability for PIP-TPGS-PAMAM treated group against Aß1-42 toxicity. PIP-TPGS-PAMAM reduced the ROS activity to 15.21% and 48.5% for free PIP treated in cell group. Similarly, extent of Aß1-42-induced apoptosis also reduced significantly from 38.2% to 12.36% in PIP-TPGS-PAMAM treated group. In addition, PIP-TPGS-PAMAM also disaggregated the Aß1-42 fibril in SHSY5Y cells. Our findings suggested that PIP-TPGS-PAMAM showed mitigation of Aß1-42-induced toxicity in neuronal cells, which can offer excellent prospect of neuroprotection and AD therapy.

Immunomodulation and Anticancer Immunity: Reviewing the Potential of Probiotics and Their Delivery with Macromolecular Carriers.

Probiotics colonize in the gastrointestinal tract and regulate the homeostasis in healthy human hosts. These protect the host against putrefactive organisms and secrete soluble factors exhibiting important transductive roles. However, constitutive processes in human host are deregulated following dysbiosis caused during prolonged exposure to cytotoxic agents and pollutants. Apart from restoring the homeostasis, probiotic administration has shown to minimize carcinogenesis and post-surgery complications in cancer patients. Moreover, ability of microbial cells to colonize at tumor foci can be harnessed to deliver genes, therapeutic proteins and antibodies in a selective manner. In this review, we have discussed immunomodulatory roles of probiotics in context to cancer prevention. The article further proposes the use of dietary interventions for boosting anticancer immunity and as an alternative to detrimental chemotherapeutic agents. After summarizing clinical evidences on probiotic efficacy, formulation approaches have been described for effective delivery of the microorganisms. The literature shows that polysaccharide matrices can be employed to achieve the survivability of probiotics. Formulation approaches have been reviewed together with the risks associated with the migration of live microorganisms to systemic circulation and their ability of transmitting antibiotic resistance factors into human pathogens.

Oxidation state of graphene oxide nanosheets drives their interaction with proteins: A case of bovine serum albumin.

In the present study, we explored the interaction of bovine serum albumin (BSA) with oxidized graphene oxide (GO) nanosheets. Nanosheets, synthesized with 4, 6, 8, 10 and 12 wt equivalents of KMnO4 as oxidant, were coded as GO-4, GO-6, GO-8, GO-10 and GO-12, respectively. After incubating sheets with a fixed concentration of BSA at room temperature, interactions were monitored with time. The analysis is based on UV-vis spectroscopy, fluorescence quenching, dynamic light scattering (DLS), small angle neutron scattering (SANS), Fourier transform infrared (FTIR) spectroscopy and circular dichroism (CD) techniques. Binding of BSA over sheets was recorded in the following order; GO-04 >> GO-06 > GO-08 > GO-10 ≈ GO-12. Our observations suggest that these interactions are largely regulated by the availability of pure graphitic domains and density of oxygen functionalities on sheet surface. This led us to the conclusion that GO-protein interactions can be minimized by modulating the extent of sheet oxidation. Moreover, we show that adsorption of proteins as colloidal aggregates contributes to improved biosafety of sheets. The protein molecule did not exhibit depletive changes in its conformation. However, from the viewpoint of drug delivery applications, density of oxygen groups must be optimized for maximizing the loading efficiency of oxidized sheets.

Relationship between the Surgical Access Line of Maxillary Posterior Teeth and the Maxillary Sinus Floor.

INTRODUCTION: The aim of this study was to use cone-beam computed tomographic imaging to investigate the relationship between the surgical access line (SAL) of maxillary posterior teeth and the maxillary sinus floor (MSF) in endodontic microsurgery. METHODS: Cone-beam computed tomographic scans of 190 subjects with clear and integrated maxillary posterior teeth and sinus floors on both sides were evaluated. The correlation of the average distance between the SAL and the MSF with age was analyzed. Three types of relationships between the SAL and MSF were classified. The minimum vertical distance between the SAL and the MSF for the type 1 relationship was measured. RESULTS: A total of 1134 teeth, including 758 premolars and 376 first molars, were evaluated. The average distance between the SAL of maxillary posterior teeth and the MSF increased with age, except in the 31- to 40-year-old group. The highest rates of the SAL touching the MSF and protruding into the maxillary sinus occurred among first molars at 25.6% and 8.1%, respectively. For the type 1 relationship, the mean distance from the SAL of the first and second premolars and the first molar to the MSF was 7.11 ± 4.40, 4.92 ± 3.69, and 4.76 ± 3.61 mm, respectively. CONCLUSIONS: Knowledge of the relationship between the SAL and the MSF of maxillary posterior teeth could provide an important reference for surgeons to evaluate surgical difficulty and decrease the risk of maxillary sinus perforation.

Further SAR studies on natural template based neuroprotective molecules for the treatment of Alzheimer's disease.

In our earlier paper, we described ferulic acid (FA) template based novel series of multifunctional cholinesterase (ChE) inhibitors for the management of AD. This report has further extended the structure-activity relationship (SAR) studies of this series of molecules in a calibrated manner to improve upon the ChEs inhibition and antioxidant property to identify the novel potent multifunctional molecules. To investigate the effect of replacement of phenylpiperazine ring with benzylpiperazine, increase in the linker length between FA and substituted phenyl ring, and replacement of indole moiety with tryptamine on this molecular template, three series of novel molecules were developed. All synthesized compounds were tested for their acetyl and butyryl cholinestrases (AChE and BChE) inhibitory properties. Enzyme inhibition and PAS binding studies identified compound 13b as a lead molecule with potent inhibitor property towards AChE/BChE (AChE IC50 = 0.96 ± 0.14 µM, BChE IC50 = 1.23 ± 0.23 µM) compared to earlier identified lead molecule EJMC-G (AChE IC50 = 5.74 ± 0.13 µM, BChE IC50 = 14.05 ± 0.10 µM, respectively). Molecular docking and dynamics studies revealed that 13b fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Trp86, Ser125, Glu202, Trp 286, Phe295, Tyr 337 in AChE, and with Trp 82, Gly115, Tyr128, and Ser287 in BChE. The compound, 13b was found to be three times more potent antioxidant in a DPPH assay (IC50 = 20.25 ± 0.26 µM) over the earlier identified EJMC-B (IC50 = 61.98 ± 0.30 µM) and it also was able to chelate iron. Co-treatment of 13b with H2O2, significantly attenuated and reversed H2O2-induced toxicity in the SH-SY5Y cells. The parallel artificial membrane permeability assay-blood brain barrier (PAMPA-BBB) revealed that 13b could cross BBB efficiently. Finally, the in-vivo efficacy of 13b at dose of 10 mg/kg in scopolamine AD model has been demonstrated. The present study strongly suggests that the naturally inspired multifunctional molecule 13b may behave as a potential novel therapeutic agent for AD management.

Recent advances in nanoparticles mediated photothermal therapy induced tumor regression.

Photothermal therapy (PTT) is a minimally invasive procedure for treating cancer. The two significant prerequisites of PTT are the photothermal therapeutic agent (PTA) and near-infrared radiation (NIR). The PTA absorbs NIR, causing hyperthermia in the malignant cells. This increased temperature at the tumor microenvironment finally results in tumor cell damage. Nanoparticles play a crucial role in PTT, aiding in the passive and active targeting of the PTA to the tumor microenvironment. Through enhanced permeation and retention effect and surface-engineering, specific targeting could be achieved. This novel delivery tool provides the advantages of changing the shape, size, and surface attributes of the carriers containing PTAs, which might facilitate tumor regression significantly. Further, inclusion of surface engineering of nanoparticles is facilitated through ligating ligands specific to overexpressed receptors on the cancer cell surface. Thus, transforming nanoparticles grants the ability to combine different treatment strategies with PTT to enhance cancer treatment. This review emphasizes properties of PTAs, conjugated biomolecules of PTAs, and the combinatorial techniques for a better therapeutic effect of PTT using the nanoparticle platform.