Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance.

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due to global demographic changes. NDs are mainly represented by degeneration/loss of neurons, which is primarily accountable for severe mental illness. This neuronal degeneration leads to many neuropsychiatric problems and permanent disability in an individual. Moreover, the tight junction of the brain, blood-brain barrier (BBB)has a protective feature, functioning as a biological barrier that can prevent medicines, toxins, and foreign substances from entering the brain. However, delivering any medicinal agent to the brain in NDs (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) is enormously challenging. There are many approved therapies to address NDs, but most of them only help treat the associated manifestations. The available therapies have failed to control the progression of NDs due to certain factors, i.e., BBB and drug-associated undesirable effects. NDs have extremely complex pathology, with many pathogenic mechanisms involved in the initiation and progression; thereby, a limited survival rate has been observed in ND patients. Hence, understanding the exact mechanism behind NDs is crucial to developing alternative approaches for improving ND patients' survival rates. Thus, the present review sheds light on different cellular mechanisms involved in NDs and novel therapeutic approaches with their clinical relevance, which will assist researchers in developing alternate strategies to address the limitations of conventional ND therapies. The current work offers the scope into the near future to improve the therapeutic approach of NDs.

Metal-organic frameworks: Drug delivery applications and future prospects.

Background and purpose: Metal-organic frameworks (MOFs) have gained incredible consideration in the biomedical field due to their flexible structural configuration, tunable pore size and tailorable surface modification. These inherent characteristics of MOFs portray numerous merits as potential drug carriers, depicting improved drug loading, site-specific drug delivery, biocompatibility, biodegradability, etc. Review approach: The current review article sheds light on the synthesis and use of MOFs in drug delivery applications. In the beginning, a brief overview of the key components and efficient fabrication techniques for MOF synthesis, along with its characterization methods, have been presented. The MOFs-based formulations have been critically discussed. The application of the design of experiments (DoE) approach to optimize MOFs has been elucidated. The MOFs-based formulations, especially the application of stimuli-responsive MOFs for site-specific drug delivery, have been deciphered. Along with drug release kinetic models, several administration methods for MOFs have also been enunciated. Subsequently, MOFs as future potential drug carriers have been elaborated. Key results and conclusion: Recently, MOFs have emerged as versatile drug delivery carriers possessing customization potential and meeting the needs of spatio-temporal drug delivery. Researchers have devised several environment-friendly approaches for MOF construction and surface modification. Owing to stimuli-responsive potential, MOFs have demonstrated their prominent therapeutic efficacy via several routes of administration. The numerous benefits of MOFs would certainly open up a new vista for its novel drug delivery applications.

Design of quetiapine fumarate loaded polyethylene glycol decorated graphene oxide nanosheets: Invitro-exvivo characterization.

Quetiapine Fumarate (QF) is an atypical antipsychotic with poor oral bioavailability (9%) due to its low permeability and pH-dependent solubility. Therefore, this study aims to design QF-loaded polyethylene glycol (PEG) functionalized graphene oxide nanosheets (GON) for nasal delivery of QF. In brief, GO was synthesized using a modified Hummers process, followed by ultra-sonication to produce GON. Subsequently, PEG-functionalized GON was prepared using carbodiimide chemistry (PEG-GON). QF was then decorated onto the cage of PEG-GON using the π-π stacking phenomenon (QF@PEG-GON). The QF@PEG-GON nanocomposite underwent several spectral characterizations, in vitro drug release, mucoadhesion study, ex vivo diffusion study, etc. The surface morphology of QF@PEG-GON nanocomposite validates the cracked nature of the nanocomposite, whereas the diffractograms and thermogram of nanocomposite confirm the conversion of QF into an amorphous form with uniform distribution in PEG-GON. Moreover, an ex vivo study of PEG-GON demonstrates superior mucoadhesion capacity due to its surface functional groups and hydrophilicity. The percent drug loading content and percent entrapment efficiency of the nanocomposite were found to be 9.2±0.62% and 92.3±1.02%, respectively. The developed nanocomposite exhibited 43.82±1.65% drug release within 24h, with the Korsemeyer-Peppas model providing the best-fit release kinetics (R2: 0.8614). Here, the interlayer spacing of PEG-GON prevented prompt diffusion of the buffer, leading to a delayed release pattern. In conclusion, the anticipated QF@PEG-GON nanocomposite shows promise as a nanocarrier platform for nasal delivery of QF.

Design of cobalt-doped graphene quantum dot-decorated vanadium pentoxide nanosheet-based Off-On fluorescent sensor system for tiopronin sensing.

Despite the high medicinal value of tiopronin, there are substantial adverse effects such as yellow skin, yellow eyes, muscle aches, etc. Therefore, there is a huge necessity to identify tiopronin using advanced sensors in provided samples. Recently, the preference for graphene quantum dots (GQDs) and inorganic nanomaterial-based fluorescent sensors for the detection of pharmaceuticals has been extensively documented due to their plentiful advantages. Therefore, in this work, the cobalt-doped GQDs decorated vanadium pentoxide nanosheet-based fluorescence switch 'Off-On' sensor (Co-GQDs@V2O5-NS) was designed for highly sensitive and selective detection of tiopronin. Briefly, the green synthesis of highly fluorescent Co-GQDs was carried out using a hydrothermal method. Meanwhile, the synthesis of V2O5-NS was synthesized using the liquid exfoliation method. The synthesis of Co-GQDs@V2O5-NS was accomplished wherein Co-GQDs adsorbed on the surface of V2O5-NS that offered the quenching of fluorescence of Co-GQDs. Afterward, the addition of tiopronin into the quenched probe disclosed the proportional recovery of fluorescence of Co-GQDs. Here, the addition of tiopronin provides the decomposition of V2O5-NS and conversion into the V4+ that aids in releasing the quenched fluorescence of Co-GQDs. The limit of detection and linearity range for tiopronin was found to be 1.43 ng/mL and 10-700 ng/mL, respectively. Moreover, it demonstrated high selectivity, good stability at experimental conditions, and practicality in analyzing tiopronin in spiked sample analysis. Hence, the designed Co-GQDs@V2O5-NS nanosized sensor enables high sensitivity, selectivity, simplicity, label-free, and eco-friendly tiopronin recognition. In the future, the utility of Co-GQDs@V2O5-NS can open a new door for sensing tiopronin in provided samples.

Chitosan and neem gum-based polyelectrolyte complex for design of allantoin loaded biocomposite film: In-vitro, ex-vivo, and in-vivo characterization.

Presently, the preference for chitosan (CS) and gum polysaccharides in biomedical applications including drug delivery and wound healing has been extensively documented. Despite this, the demerits of CS and gum polysaccharides such as poor mechanical properties, degradation rate, swelling, etc., limit their applications for designing biocomposite films for drug delivery. Therefore, the anticipated work aims to design a CS and neem gum polysaccharides (NGP) polyelectrolyte complex-based allantoin (AT)-loaded (CS/NGP-AT) biocomposite film for improved wound healing. In brief, CS, NGP, and CS/NGP-AT-based biocomposite films were prepared using the solvent-casting method, and in-vitro, ex-vivo, and in-vivo characterizations were performed to assess the performance of these biocomposite films compared to their counterparts. In this, diffractogram and thermogram analysis assured the conversion of crystalline AT into an amorphous form. The optimized CS/NGP/AT-3 formulation exhibited controlled water absorption, appropriate water uptake capacity, good water retention ability, excellent water vapor transmission rate, controlled degradation rate, enhanced mechanical properties, cell and blood biocompatibility, etc. Furthermore, it offered improved antimicrobial, anti-inflammatory, and antioxidant potential. The optimized film provided a modified release (88.3 ± 0.3 %) of AT from the film for up to 48 h. Wound healing experiments on rats and their histopathology studies confirmed a significantly higher rate of wound recovery within 14 days compared to the control and CS/NGP film, attributable to the combined effects of CS, NGP, and AT. In conclusion, the fabricated CS/NGP-based biocomposite film presents promising prospects as an excellent candidate for wound healing applications.

Pharmacokinetics of vitamin dosage forms: A complete overview.

Vitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier-based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency.

Formulation of lactoferrin decorated dextran based chitosan-coated europium metal-organic framework for targeted delivery of curcumin.

Hepatocellular carcinoma (HPTC) currently ranks as the third leading cause of cancer-related mortality, necessitating an advanced formulation strategy. Recently, lactoferrin (Lf) has been utilized as a specific targeting ligand in HPTC due to its high specificity towards the asialoglycoprotein receptor expressed in cancer cells. Therefore, we present the fabrication of an Lf-decorated carboxymethyl dextran-encased chitosan-coated europium metal-organic framework-based nanobioconjugate (Lf-CMD-CS-CUR@Eu-MOF) for targeted curcumin (CUR) delivery. Briefly, CUR was loaded into Eu-MOF, followed by coating cationic 'CS' on the CUR@Eu-MOF surface. Simultaneously, Lf-decorated CMD was prepared via an esterification reaction. Subsequently, Lf-CMD-CS-CUR@Eu-MOF was synthesized using the Maillard reaction. Various spectral characterizations, drug entrapment, drug content, in vitro drug release, biocompatibility and cell cytotoxicity studies were performed. It exhibited an entrapment efficiency of 88.87 ± 2.1 %, a drug content of 3.45 ± 0.98 %, and a drug loading rate of 34.85 ± 0.6 mg/g. Furthermore, the Lf-CMD-CS-CUR@Eu-MOF exhibits excellent biocompatibility with normal cells. The in vitro dissolution study confirmed a release of 78.12 % of 'CUR' in pH 5.8 phosphate buffer (over 120 h), attributed to the controlled release rate by the 'CS' coating on the surface of CUR@Eu-MOF. The BEL-7402 cell line showed concentration-dependent toxicity of nanobioconjugate to cancerous cells. Therefore, when 'Lf' is surface-decorated onto an appropriate polymeric material, it gains the capability to function as a carrier for transporting 'CUR' to the precise target site within HPTC. In conclusion, Lf-CMD incorporated CS-coated Eu-MOF can provide a promising approach for targeted drug delivery in HPTC management.

Design of lactoferrin functionalized carboxymethyl dextran coated egg albumin nanoconjugate for targeted delivery of capsaicin: Spectroscopic and cytotoxicity studies.

The increased mortality rates associated with colorectal cancer highlight the pressing need for improving treatment approaches. While capsaicin (CAP) has shown promising anticancer activity, its efficacy is hampered due to low solubility, rapid metabolism, suboptimal bioavailability, and a short half-life. Therefore, this study aimed to prepare a lactoferrin-functionalized carboxymethyl dextran-coated egg albumin nanoconjugate (LF-CMD@CAP-EGA-NCs) for the targeted CAP delivery to enhance its potential for colorectal cancer therapy. Briefly, LF-CMD was synthesized through an esterification reaction involving LF as a receptor and CMD as a shell. Concurrently, CAP was incorporated into an EGA carrier using gelation and hydrophobic interactions. The subsequent production of LF-CMD@CAP-EGA-NCs was achieved through the Maillard reaction. Spectral characterizations confirmed the successful synthesis of smooth and spherical-shaped LF-CMD@CAP-EGA-NCs using LF-CMD and EGA-CAP nanoparticles, with high entrapment efficiency and satisfactory drug content. Furthermore, LF-CMD@CAP-EGA-NCs demonstrated a sustained release of CAP (76.52 ± 1.01 % in 24 h, R2 = 0.9966) in pH 5.8 buffer with anomalous transport (n = 0.68) owing to the shell of the CMD and EGA matrix. The nanoconjugate exhibited enhanced cytotoxicity in HCT116 and LoVo cell lines, which is attributed to the overexpression of LF receptors in colorectal HCT116 cells. Additionally, LF-CMD@CAP-EGA-NCs demonstrated excellent biocompatibility, as observed in the FHC-CRL-1831 cell line. In conclusion, LF-CMD@CAP-EGA-NCs can be considered as a promising approach for targeted delivery of CAP and other anticancer agents in colorectal cancer treatment.

Zinc metal-organic frameworks- graphene quantum dots nanocomposite mediated highly sensitive and selective fluorescence "On-Off-On" probe for sensing of quercetin.

Presently, there is a necessity to design novel methods because of quercetin's significant biological relevance. Therefore, we developed the rose petal-derived graphene quantum dots embedded zinc metal organic frameworks (RP-GQDs@Zn-MOFs) based fluorescence "On-Off-On" nanoprobe for quercetin sensing. Initially, RP-GQDs were synthesized using rose petal waste and then subjected to embedding into Zn-MOFs. Herein, the addition of copper ions (Cu2+) results in fluorescence "Switch Off" whereas quercetin inclusion resulted in the formation of the quercetin-Cu2+ complex. It regains the RP-GQDs@Zn-MOFs quenched fluorescence termed as "Switch On" because of the static quenching mechanism. It demonstrated a wide concentration range and low detection limit of 100 ng/mL to 1400 ng/mL (R2=0.99) and 37.84 ng/mL, respectively. The selectivity study shows the high specificity for quercetin in presence of interfering compounds because of Cu2+ coordination between the carbonyl oxygen atom and the 3-OH group of quercetin. Moreover, the designed probe shows good stability, repeatability, and real-time analysis possibility.

Stimuli-Responsive Design of Metal-Organic Frameworks for Cancer Theranostics: Current Challenges and Future Perspective.

Scientific fraternity revealed the potential of stimuli-responsive nanotherapeutics for cancer treatment that aids in tackling the major restrictions of traditionally reported drug delivery systems. Among stimuli-responsive inorganic nanomaterials, metal-organic frameworks (MOFs) have transpired as unique porous materials displaying resilient structures and diverse applications in cancer theranostics. Mainly, it demonstrates tailorable porosity, versatile chemical configuration, tunable size and shape, and feasible surface functionalization, etc. The present review provides insights into the design of stimuli-responsive multifunctional MOFs for targeted drug delivery and bioimaging for effective cancer therapy. Initially, the concept of cancer, traditional cancer treatment, background of MOFs, and approaches for MOFs synthesis have been discussed. After this, applications of stimuli-responsive multifunctional MOFs-assisted nanostructures that include pH, light, ions, temperature, magnetic, redox, ATP, and others for targeted drug delivery and bioimaging in cancer have been thoroughly discussed. As an outcome, the designed multifunctional MOFs showed an alteration in properties due to the exogenous and endogenous stimuli that are beneficial for drug release and bioimaging. The several reported types of stimuli-responsive surface-modified MOFs revealed good biocompatibility to normal cells, promising drug loading capability, target-specific delivery of anticancer drugs into cancerous cells, etc. Despite substantial progress in this field, certain crucial issues need to be addressed to reap the clinical benefits of multifunctional MOFs. Specifically, the toxicological compatibility and biodegradability of the building blocks of MOFs demand a thorough evaluation. Moreover, the investigation of sustainable and greener synthesis methods is of the utmost importance. Also, the low flexibility, off-target accumulation, and compromised pharmacokinetic profile of stimuli-responsive MOFs have attracted keen attention. In conclusion, the surface-modified nanosized design of inorganic diverse stimuli-sensitive MOFs demonstrated great potential for targeted drug delivery and bioimaging in different kinds of cancers. In the future, the preference for stimuli-triggered MOFs will open a new frontier for cancer theranostic applications.

Platinum-alginate-chitosan nanobioconjugate decorated carbon backbone layered biosensor for highly sensitive and selective detection of BACE-1.

Chitosan (CS) and sodium alginates (SA) have been revealed for the design of layer-by-layer (LbL) assembly to develop pharmaceutical dosage forms owing to their versatile characteristics. Recently, the preference for unique LbL assemblies in biosensor development has offered the modified performance for detection interest analyte. Beta (ß)-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) is a pivotal biomarker of Alzheimer's disease (AD) and demands high sensitivity and selective identification for the early-stage diagnosis. In this work, CS-SA­platinum nanoparticles (Pt-NPs) LbL-based nanobioconjugate decorated carbon backbone-layered affinity surface plasmon resonance (Anti-BACE-1-LbL@Pt-NPs-GO-SPR) biosensor was designed for extremely sensitive and selective sensing of BACE-1. Primarily, LbL nanobioconjugate was synthesized by integrating cationic 'CS' and anionic 'SA' on the face of green-made Pt-NPs. Here, the amines of 'CS' offers a softer surface for anti-BACE-1 immobilization that leads to maintaining the bio-functionality of bioreceptors, provides the specific orientation for bioreceptors, etc. As well, the synthesized graphene oxide (GO, 2D carbon backbone) was preferred as non-plasmonic nanomaterials due to their plenty of merits in biosensors. Here, the designed biosensor provides a low detection limit (LOD) of 5.63 fg/mL and a wide linear range from 5 fg/mL to 150 ng/mL. Moreover, selectivity and real-time analyses in spiked samples exhibited their practical usefulness in complex specimens for BACE-1 detection. Hence, the decorating of antibody-immobilized CS-SA coated Pt-NPs nanobioconjugate on the face of GO has various benefits mainly extremely sensitive and superb specificity. Overall, CS and SA coated Pt-NPs bioconjugate decorated GO layered SPR biosensors can provide highly sensitive, selectivity, rapid, label-free, etc. detection of BACE-1 in clinical samples.

Poly(allylamine) coated layer-by-layer assembly decorated 2D carbon backbone for highly sensitive and selective detection of Tau-441 using surface plasmon resonance biosensor.

The determination of clinically significant amounts of tau protein in bodily fluids is a major problem in Alzheimer's disease (AD) diagnosis. As a result, the present work aims to develop a simple, label-free, fast, highly sensitive, and selective 2D carbon backbone graphene oxide (GO) patterned surface plasmon resonance (SPR) mediated affinity biosensor for Tau-441 monitoring. Initially, non-plasmonic nanosized GO was made using a modified Hummers' method, whereas green synthesized gold nanoparticles (AuNPs) were subjected to a layer-by-layer (LbL) design employing anionic and cationic polyelectrolytes. Several spectroscopical evaluations were carried out to ensure the synthesis of GO, AuNPs, and LbL assembly. Following that, the Anti-Tau rabbit antibody was immobilized on the designed LbL assembly using carbodiimide chemistry, and various studies such as sensitivity, selectivity, stability, repeatability, spiked sample analysis, etc., were conducted using the constructed affinity GO@LbL-AuNPs-Anti-Tau SPR biosensor. As an output, it shows a broad concentration range and a very low detection limit of 150 ng/mL to 5 fg/mL and 13.25 fg/mL, respectively. The remarkable sensitivity of this SPR biosensor represents the merits of a combination of plasmonic AuNPs and a non-plasmonic GO. It also exhibits great selectivity for Tau-441 in the presence of interfering molecules, which may be because of the immobilization of the Anti-Tau rabbit on the surface of the LbL assembly. Furthermore, it ensured high stability and repeatability, while spiked sample analysis and AD-induced animal samples analysis confirmed the practicability of GO@LbL-AuNPs-Anti-Tau SPR biosensor for Tau-441 detection. In conclusion, fabricated sensitive, selective, stable, label-free, quick, simple, and minimally invasive GO@LbL-AuNPs-Anti-Tau SPR biosensor will provide an alternative for AD diagnosis in the future.

Design of polyacrylamide grafted sesbania gum-mediated pH-responsive IPN-based microbeads for delivery of diclofenac sodium: In-vitro-in-vivo characterizations.

Microwave-assisted grafting of polyacrylamide on sesbania gum (PAAM-g-SG) was implemented employing a 32 full factorial experimental design and was hydrolyzed using sodium hydroxide (NaOH) to form H-PAAM-g-SG. Further, the diclofenac sodium-loaded novel pH-sensitive interpenetrating polymeric network (IPN) microbeads were designed using an optimized H-PAAM-g-SG and sodium alginate (SA). Different spectroscopic analysis including FTIR spectroscopy, 1H NMR spectroscopy, elemental analysis, thermal analysis, etc. was performed to confirm the synthesis of PAAM-g-SG and diclofenac-loaded pH-sensitive IPN H-PAAM-g-SG-SA microbeads. Here, Ca+2 ions combine with two strands of SA and form a round-shape structure that encloses uncross-linked H-PAAM-g-SG polymer and diclofenac sodium. As well, glutaraldehyde (GL) addition improved the mechanical strength due to acetal structure between hydroxyl of H-PAAM-g-SG and aldehyde of GL. The drug entrapment was confirmed proportional relationship to the Ca+2 ions concentration whereas an increase in GL concentration resulted in a reduced drug entrapment. The pH pulsatile study assured the reversible swelling-shrinkage behavior of IPN microbeads due to the carboxyl group of PAAM-g-SG. The drug release from H-PAAM-g-SG-SA microbeads (batch: S9) was found to be 84.21 % (12h) which was non-significant (p > 0.05; f2 = 79 âˆ¼ 90) over marketed formulation (83.31 %). Moreover, it follows the Korsmeyer Peppas (R2 = 0.996) as the best-fit release kinetic model. The pH-sensitive release of diclofenac sodium from IPN H-PAAM-g-SG-SA microbeads was assured based on in vivo anti-inflammatory activity (p < 0.05). Therefore, developed novel pH-sensitive IPN microbeads based on H-PAAM-g-SG are a promising polymeric carrier substitute for delivery of drugs actuated by a pH stimulus.

Black Phosphorus Nanostructure Based Highly Sensitive and Selective Surface Plasmon Resonance Sensor for Biological and Chemical Sensing: A Review.

Surface plasmon resonance (SPR) is an attention-grabbing sensor type, which offers the sensitive and selective detection of biomolecules and environmentally toxic substances. Notably, the SPR sensor gives excellent rewards including real-time, in-situ, and label-free measuring capability as compared to existing sensing technologies. As a result, these noteworthy merits of the SPR sensor make it straightforward to investigate the molecular events and chemical/gas molecule interaction. Unfortunately, there are different binding events including smaller molecular mass substances, which cannot be detected at the SPR sensor. Accordingly, this downside of the SPR sensor eventually led to the design and implementation of new approaches for sensitivity and selectivity improvement for sensing applications in different fields. Recently, the black phosphorus (BP) derived 2 D nanomaterial is stand out as a distinctive nanostructure in comparison to recently reported other 2 D nanomaterials. Substantial and functional characteristics of BP including simplicity of operation, optical properties, high carrier mobility, stronger immobilization of receptors and biomolecules, electronic bridging playing important role in the highly selective and sensitive assessment of analyte. The designed BP nanostructures are mostly serving to accelerate the plasmon material signals followed by improved molecular sensing that may due to 40-times faster-sensing responses of BP nanostructure than reported 2 D nanomaterials. Therefore, the present review article sheds light on the latest significant advances in biological and toxic gas detection through 2D BP nanostructures based SPR sensors. In the future, this review will facilitate detailed insights into the development of BP-based groundbreaking frameworks for highly sensitive and selective recognition of biomolecules and environmental pollutants.

Design of surface tailored carboxymethyl dextran-protein based nanoconjugates for paclitaxel: Spectroscopical characterizations and cytotoxicity assay.

Paclitaxel (PTX) is an essential anticancer drug from the biopharmaceutical classification system (BCS) class IV. Unfortunately, PTX has some drawbacks including low solubility, cell toxicity, adverse cell reaction, etc. Therefore, folic acid (FA) tailored carboxymethyl-dextran (CMD), and bovine serum albumin (BSA) mediated nanoconjugates of paclitaxel (PTX) (FA-CMD-BSA-PTX) were designed. At first, esterification reaction between FA and CMD resulted in FA-CMD conjugate whereas FA-CMD-BSA conjugate was synthesized via the Maillard reaction. Finally, FA-CMD-BSA conjugates of PTX were achieved via hydrophobic interaction and gelation of BSA. Herein, heating offers the gelation of BSA that furnishes the cross-linking wherein PTX gets fixed inside BSA. Thermogram of FA-CMD-BSA-PTX showed the absence of PTX peak that concluding PTX has been molecularly dispersed in polymer matrix and entrapment inside polymeric conjugate. As an effect, surface decorated FA-CMD-BSA-PTX showed low hemolytic toxicity over free PTX. Cytotoxicity assay on A549 human lung cancer cells shows cell viability decreased from 60 % to 10 % with increasing concentration from 1 to 5 µg/mL. In conclusion, CMD facilitates the circulation time of PTX and BSA acts as a carrier to target tumor locations effectively. The nano-conjugate formulation significantly reduces toxicity and can be used for the treatment of lung cancer.

Formulation, optimization, and in-vitro-ex-vivo evaluation of dual-crosslinked zinc pectinate-neem gum-interpenetrating polymer network mediated lansoprazole loaded floating microbeads.

Low methoxy pectin (LM pectin) suffers from burst release owing to its high swellability and solubility in water. Consequently, in ways to design an ideal drug delivery system, these obstacles must be surmounted. Therefore, the work aimed to design dual crosslinked LM pectin -neem gum (NG) mediated interpenetrating polymer network (IPN) floating mucoadhesive microbeads for lansoprazole (LNZ) gastro-retentive delivery. In short, LNZ-loaded floating microbeads were achieved by using the ionic gelation method wherein zinc acetate was preferred as a crosslinking agent. The optimization of IPN microbeads was performed employing a 32factorial design wherein concentration of pectin and NG was considered as independent factors whereas dependant factors are entrapment efficiency and drug release. Importantly, carboxylic functionality of low methoxy (LM) pectin and hydroxylic functionality NG cross-linked with Zn+2 forms a 3D network. Diffractogram and thermogram revealed that conversion of drug from crystalline to amorphous form because of entrapment of drug within polymeric network. Anticipated floating microbeads showed that polymer concentration had considerable effect on drug encapsulation efficiency and drug release. Briefly, optimizing floating microbeads (Batch B:5) showed maximum drug entrapment (87.47 %) with a delayed drug release (69.20 %, at 8 h) due to formation of strong IPN. Moreover, it showed good mucoadhesive aptitude with goat stomach mucosa because of entanglement between gum and mucus layer. In addition, use of calcium silicate assists to modulate floating profile of IPN microbeads. Therefore, designing dual crosslinked zinc-pectinate-NG mediated IPN floating mucoadhesive microbeads will offer a new substitute for floating delivery.

Design of "Turn-Off" Fluorescent Nanoprobe for Highly Sensitive Detection of Uric Acid using Green Synthesized Nitrogen-Doped Graphene Quantum Dots.

Green synthesized graphene quantum dots (GQD) have been doped with nitrogen in an attempt to boost their optical characteristics and application sectors. In the present investigation, the blue luminescent nitrogen-doped GQDs (N-GQDs) were synthesized by single-step hydrothermal synthesis using tamarind shell powder as a precursor. The particle size and zeta potential of N-GQDs were found to be 11.40 nm and be -35.53 mV, respectively. A quantum yield as high as 23.78 % was accomplished at an excitation wavelength of 330 nm at neutral pH. It gets quenched sensitively in the existence of uric acid (UA) combining static quenching, electron transfer, and an inner filter effect mechanism. A linear range was obtained for UA from 10 µM to 100 µM, with a limit of detection (LOD) of 401.72 ± 0.04 pM. Additionally, the N-GQDs were selective toward UA in presence of metal ions and biomolecules that indicated its impending use to monitor UA in clinical samples. In conclusion, this work demonstrates that the N-GQDs as a sensing probe for UA recognition with notable advantages including socioeconomic, simple, and less time-consuming methods as compared to other methods. In the future, it can be potentially explored as a biosensor for UA detection in clinical samples.

Chitosan mediated layer-by-layer assembly based graphene oxide decorated surface plasmon resonance biosensor for highly sensitive detection of ß-amyloid.

Alzheimer's disease (AD), and its consequent effect primarily clinical dementia, Parkinson's disease dementia, etc. currently bring potential avenues for diagnosis centered on identification of beta-amyloid1-42 (Aß1-42). Unfortunately, techniques engaged in AD core biomarker (Aß1-42) detection are majorly suffering from poor sensitivity and selectivity. Thus, we fabricated graphene oxide (GO) surface decorated chitosan (CS) mediated layer-by-layer (LbL) assembly based surface plasmon resonance (SPR) biosensor for highly sensitive and selective recognition of Aß1-42. Briefly, silver nanoparticles (AgNPs) and GO synthesis were achieved through a greener approach. LbL assembly was designed using CS and polystyrene sulphonate (PSS) on surface of AgNPs (AgNPs-CS-PSS-CS) and then antibodies of Aß (anti-Aß) were fixed on LbL assembly (AgNPs-CS-PSS-CS@anti-Aß). Herein, amine functionality of CS offers a plethora of sites for anti-Aß antibody immobilization that gives specific direction, high selectivity, and an adequate amount of antibody immobilization. For fabrication, synthesized GO was immobilized on an amine-modified gold-coated sensor chip via carbodiimide chemistry followed by AgNPs-CS-PSS-CS@anti-Aß immobilization on an activated GO surface. Inimitable features of LbL assembly showed improved selectivity towards Aß peptide whereas utilization of affinity biotransducer with a combination of plasmonic and non-plasmonic nanomaterial improved sensitivity and selectivity. Consequently, linearity range and limit of detection (LOD) of Aß1-42 antigens were found to be 2 fg/mL to 400 ng/mL and 1.21 fg/mL, respectively. Moreover, analysis of Aß1-42 in AD-induced rats confirmed the real-time-applicability of the designed SPR biosensor. Hence, GO surface decorated AgNPs-CS-PSS-CS@anti-Aß mediated SPR biosensor would provide a novel approach for exceptionally sensitive and selective Aß detection.

Nanoarchitectured Bioconjugates and Bioreceptors Mediated Surface Plasmon Resonance Biosensor for In Vitro Diagnosis of Alzheimer's Disease: Development and Future Prospects.

Alzheimer's disease (AD) is an obvious neurological disorder characterized by progressive brain cell death that resulted in memory loss, cognitive decline, and finally dementia. Besides, AD is also affected by a multifunctional pathway, which leads to alteration in the biomolecular level as AD steps forward. Notwithstanding numerous diagnosis techniques, the conventionally engaged technology permits the detection of AD biomarkers with low sensitivity and poor selectivity. Concerning this, in recent years bioconjugates and bioreceptors based AD biomarkers recognition is gaining huge prospective to improved selectivity and sensitivity of AD at the molecular level. The present review deals with the recent progress in bioreceptors and bioconjugates mediated surface plasmon resonance (SPR) biosensor for in vitro diagnosis of AD. Fascinatingly, this review inculcates the information of assorted important AD biomarkers viz. beta-amyloid (Aß), Tau protein, apolipoprotein (apoE4), 17-ß-hydroxysteroid dehydrogenase type 10 (17ß-HSD-10), acetylcholine, etc. In addition, this review sheds light on the utmost and unique methods of bioconjugates synthesis, which is holding the huge attention of researchers for AD biomarker detection and contributed to the development of simplistic, rapid, and socioeconomic sensitivity enhancement methods. Concisely, this review gives insight into the analytical performance of nanoarchitectured bioconjugate and bioreceptor-mediated SPR biosensor and their revolutionary benefits in terms of selectivity and sensitivity for in vitro diagnosis of AD biomarkers. Overall, this review gives a detailed overview of research done to date in the meadow of SPR biosensors in the in vitro diagnosis of AD, which paves the new pathway for futuristic biomedical applications. Highlights AD recent updates and its biomarkers reviewed. There is no leading technology to rapidly sense and monitor AD. Bioconjugates as potential biosensing elements. Conjugation methods to link bioreceptors to nanomaterials have been highlighted. Role of bioconjugates and bioreceptors in AD biosensing through SPR biosensor have been discussed.

Graphene quantum dots (GQDs) nanoarchitectonics for theranostic application in lung cancer.

Lung cancer (LC) is heading up as a substantial cause of mortality worldwide. Despite enormous progress in cancer management, LC remains a crucial problem for oncologists due to the lack of early diagnosis and precise treatment. In this context, numerous early diagnosis and treatment approaches for LC at the cellular level have been developed using advanced nanomaterials in the last decades. Amongst this, graphene quantum dots (GQDs) as a novel fluorescent material overwhelmed the horizons of materials science and biomedical fields due to their multifunctional attributes. Considering the complex nature of LC, emerging diagnostic and therapeutic (Theranostics) strategies using GQDs proved to be an effective way for the current practice in LC. In this line, we have abridged various approaches used in the LC theranostics using GQDs and its surface-engineered motif. The admirable photophysical attributes of GQDs realised in photolytic therapy (PLT), hyperthermia therapy (HTT), and drug delivery have been discussed. Furthermore, we have engrossed the impasse and its effects on the use of GQDs in cancer treatments from cellular level (in vivo-in vitro) to clinical. Inclusively, this review will be an embodiment for the scientific fraternity to design and magnify their view for the theranostic application of GQDs in LC treatment.