Selective detection of azelnidipine in pharmaceuticals via carbon dot mediated spectrofluorimetric method: A green approach.

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 µg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

Clozapine-laden carbon dots delivered to the brain via an intranasal pathway: Synthesis, characterization, ex vivo, and in vivo studies.

Clozapine, which is widely used to treat schizophrenia, shows low bioavailability due to poor solubility and high first-pass metabolism. The study aimed to design clozapine-loaded carbon dots (CDs) to enhance availability of the clozapine to the brain via intranasal pathway. The CDs were synthesized by pyrolysis of citric acid and urea at 200 °C by hydrothermal technique and characterized by photoluminescence, transmission electron microscopy (TEM), X-ray Photoelectron Spectrometer (XPS), and Fourier transform infrared spectrum (FTIR). The optimized clozapine-loaded CDs (CLZ-CDs-1:3-200) showed a quasi-spherical shape (9-12 nm) with stable blue fluorescence. The CDs showed high drug solubilization capacity (1.5 mg drug in 1 mg/ml CDs) with strong electrostatic interaction with clozapine (drug loading efficiency = 94.74%). The ex vivo release study performed using nasal goat mucosa showed sustained release of clozapine (43.89%) from CLZ-CDs-1:3-200 for 30 h. The ciliotoxicity study (histopathology) confirmed no toxicity to the nasal mucosal tissues using CDs. In the rat model (in vivo pharmacokinetic study), when CDs were administrated by the intranasal route, a significantly higher concentration of clozapine in the brain tissue (Cmax = 58.07 ± 5.36 µg/g and AUCt (µg/h*g) = 105.76 ± 12.31) was noted within a short time (tmax = 1 h) compared to clozapine suspension administered by intravenous route (Cmax = 20.99 ± 3.91 µg/g, AUC t (µg/h*g) = 56.89 ± 12.31, and tmax = 4 h). The high value of drug targeting efficiency (DTE, 486%) index and direct transport percentage (DTP, 58%) indicates the direct entry of clozapine-CDs in the brain via the olfactory route. In conclusion, designed CDs demonstrated a promising dosage form for targeted nose-to-brain delivery of clozapine for the effective treatment of schizophrenia.

Development of a highly sensitive fluorescent probe using Delonix regia (Gulmohar) tree pod shell for precise sarcosine detection in human urine samples: advancing prostate cancer diagnosis.

We designed a highly sensitive fluorescent sensor for the early detection of sarcosine, a potential biomarker for prostate cancer. This sensor was based on surface-cobalt-doped fluorescent carbon quantum dots (Co-CD) using a FRET-based photoluminescent sensing platform. Blue luminescent carbon quantum dots (CQD) were synthesised through a hydrothermal approach, utilizing Delonix regia tree pod shells. Cobalt was employed to functionalize the CQD, enhancing the quantum-entrapped effects and minimizing surface flaws. To optimize Co-CD preparation, we employed a Box-Behnken design (BBD), and response surface methodology (RSM) based on single-factor experiments. The Co-CD was then used as a fluorescent probe for selective Cu2+ detection, with Cu2+ quenching Co-CD fluorescence through an energy transfer process, referred to as 'turn-off'. When sarcosine was introduced, the fluorescence intensity of Co-CD was restored, creating a 'turn-on' response. The sensor exhibited a Cu2+ detection limit (LOD) of 2.4 µM with a linear range of 0 µM to 10 µM. The sarcosine detection in phosphate buffer saline (PBS, pH 7.4) resulted in an LOD of 1.54 µM and a linear range of 0 to 10 µM. Importantly, the sensor demonstrated its suitability for clinical analysis by detecting sarcosine in human urine. In summary, our rapid and highly sensitive sensor offers a novel approach for the detection of sarcosine in real samples, facilitating early prostate cancer diagnosis.Communicated by Ramaswamy H. Sarma.

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.

Affinity-Based Nanoarchitectured Biotransducer for Sensitivity Enhancement of Surface Plasmon Resonance Sensors for In Vitro Diagnosis: A Review.

Despite the indisputable benefits and advancement of science, technology, and civilization, early diagnosis of healthcare is still a challenging field for the scientific fraternity. The detection of biomarkers is a crucial attribute of prognosis and diagnosis of disease. Out of numerous techniques, surface plasmon resonance (SPR) bestows countless benefits, including in situ, label-free, and real-time assessment, etc., which authorizes the analysis of molecular binding occurrences between biotransducers and biomarkers. In addition, SPR with low-molecular-weight biomarkers lacks selectivity and sensitivity, which ultimately affects binding kinetics. This, in turn, leads to the remarkable development and implementation of numerous selectivity and sensitivity enhancement methods. Among the various noticeable strategies, because of selectivity and sensitivity enrichment substrate for SPR biosensors, affinity-based nanoarchitectured biotransducers stand out as being the best substitute. The present review elaborates significant advances made in the research based on affinity biotransducers for in vitro diagnosis using SPR biosensors for biomarker sensing. Moreover, most recent trends and challenges in designing and application of nanoarchitectured affinity biotransducer-based SPR biosensors for detecting low-concentration biomarkers have been reviewed comprehensively. This present review may assist the scientific fraternity in designing an ultramodern novel SPR approach based on affinity biotransducers, along with improved selectivity and sensitivity of SPR biosensors for in vitro and real-time diagnostic applications.

Black Phosphorus as Multifaceted Advanced Material Nanoplatforms for Potential Biomedical Applications.

Black phosphorus is one of the emerging members of two-dimensional (2D) materials which has recently entered the biomedical field. Its anisotropic properties and infrared bandgap have enabled researchers to discover its applicability in several fields including optoelectronics, 3D printing, bioimaging, and others. Characterization techniques such as Raman spectroscopy have revealed the structural information of Black phosphorus (BP) along with its fundamental properties, such as the behavior of its photons and electrons. The present review provides an overview of synthetic approaches and properties of BP, in addition to a detailed discussion about various types of surface modifications available for overcoming the stability-related drawbacks and for imparting targeting ability to synthesized nanoplatforms. The review further gives an overview of multiple characterization techniques such as spectroscopic, thermal, optical, and electron microscopic techniques for providing an insight into its fundamental properties. These characterization techniques are not only important for the analysis of the synthesized BP but also play a vital role in assessing the doping as well as the structural integrity of BP-based nanocomposites. The potential role of BP and BP-based nanocomposites for biomedical applications specifically, in the fields of drug delivery, 3D printing, and wound dressing, have been discussed in detail to provide an insight into the multifunctional role of BP-based nanoplatforms for the management of various diseases, including cancer therapy. The review further sheds light on the role of BP-based 2D platforms such as BP nanosheets along with BP-based 0D platforms-i.e., BP quantum dots in the field of therapy and bioimaging of cancer using techniques such as photoacoustic imaging and fluorescence imaging. Although the review inculcates the multimodal therapeutic as well as imaging role of BP, there is still research going on in this field which will help in the development of BP-based theranostic platforms not only for cancer therapy, but various other diseases.

Perspectives of characterization and bioconjugation of gold nanoparticles and their application in lateral flow immunosensing.

Gold nanoparticles (AuNPs) are an important component in the field of biomedical diagnostics. Because of its unique physicochemical properties, AuNPs have been widely used in biomedical applications such as photothermal cancer therapy, drug delivery, optical imaging, labeling, and biosensing. In this review, we have described synthesis and characterization techniques for AuNPs with recent advancements. Characterization of AuNPs has played an important role in directing its application in various fields and elaborated understanding of its functioning. The characterization techniques used for the analysis of AuNPs utilize its intrinsic properties, such as surface plasmon resonance (SPR) and size-dependent shift in absorption. These properties of AuNPs are furthermore used for the characterization of bioconjugated AuNPs. Surface conjugation of the AuNPs with biomolecules is explored widely for its use in numerous biosensing applications. Biosensor-based diagnostic devices use AuNPs conjugated with a sensing probe for the detection of a specific analyte. AuNPs are also commonly used as a colorimetric sensor in various point-of-care diagnostic techniques. Lateral flow immunosensing (LFIS) technique utilizes AuNPs for the rapid and sensitive detection of various analytes. LFIS is a paper-based detection technique, where the sample containing the analyte flows through the membrane, interacts with immobilized counterparts, and produces results using a detection probe. AuNPs are used as color markers in LFIS, and the presence of an analyte is indicated by the appearance of colored lines on the membrane. The color is a result of the accumulation of AuNP complexes containing the analyte and probe. Effect of characterization parameters of AuNPs on the sensitivity of LFIS, advantages, and disadvantages of using AuNPs for LFIS are discussed concerning the recent reports. Recent applications of AuNPs in LFIS development for the detection of various biomarkers are summarized comprehensively in the table. The review may offer significant insight into the utility of AuNPs for application in the LFIS technique for future development. Graphical abstract Schematic representation of the various applications of gold nanoparticles.

Recent Advancement in Bio-precursor derived graphene quantum dots: Synthesis, Characterization and Toxicological Perspective.

Graphene quantum dots (GQDs), impressive materials with enormous future potential, are reviewed from their inception, including different precursors. Considering the increasing burden of industrial and ecological bio-waste, there is an urgency to develop techniques which will convert biowaste into active moieties of interest. Amongst the various materials explored, we selectively highlight the use of potential carbon containing bioprecursors (e.g. plant-based, amino acids, carbohydrates), and industrial waste and its conversion into GQDs with negligible use of chemicals. This review focuses on the effects of different processing parameters that affect the properties of GQDs, including the surface functionalization, paradigmatic characterization, toxicity and biocompatibility issues of bioprecursor derived GQDs. This review also examines current challenges and s the ongoing exploration of potential bioprecursors for ecofriendly GQD synthesis for future applications. This review sheds further light on the electronic and optical properties of GQDs along with the effects of doping on the same. This review may aid in future design approaches and applications of GQDs in the biomedical and materials design fields.

Theranostic Prospects of Graphene Quantum Dots in Breast Cancer.

Breast cancer (BC) is increasing as a significant cause of mortality among women. In this context, early diagnosis and treatment strategies for BC are being developed by researchers at the cellular level using advanced nanomaterials. However, immaculate etiquette is the prerequisite for their implementation in clinical practice. Considering the stolid nature of cancer, combining diagnosis and therapy (theranostics) using graphene quantum dots (GQDs) is a prime focus and challenge for researchers. In a nutshell, GQDs is a new shining star among various fluorescent materials, which has acclaimed fame in a short duration in materials science and the biomedical field as well. From this perspective, we review various strategies in BC treatment using GQDs alone or in combination. In addition, the photophysical properties of GQDs explored in photothermal therapy, hyperthermia therapy, and photodynamic therapy are also discussed. Moreover, we also focus on the strategic use of GQDs both as drug carriers and as combinatorial-guided drug delivery motifs. This Review provides an update for the scientific community to plan and expand advanced theranostic horizons in BC using GQDs.

Graphene-based nanocomposites for sensitivity enhancement of surface plasmon resonance sensor for biological and chemical sensing: A review.

Surface plasmon resonance (SPR) offers exceptional advantages such as label-free, in-situ and real-time measurement ability that facilitates the study of molecular or chemical binding events. Besides, SPR lacks in the detection of various binding events, particularly involving low molecular weight molecules. This drawback ultimately resulted in the development of several sensitivity enhancement methodologies and their application in the various area. Among graphene materials, graphene-based nanocomposites stands out owing to its significant properties such as strong adsorption of molecules, signal amplification by optical, high carrier mobility, electronic bridging, ease of fabrication and therefore, have established as an important sensitivity enhancement substrate for SPR. Also, graphene-based nanocomposites could amplify the signal generated by plasmon material and increase the sensitivity of molecular detection up to femto to atto molar level. This review focuses on the current important developments made in the potential research avenue of SPR and fiber optics based SPR for chemical and biological sensing. Latest trends and challenges in engineering and applications of graphene-based nanocomposites enhanced sensors for detecting minute and low concentration biological and chemical analytes are reviewed comprehensively. This review may aid in futuristic designing approaches and application of grapheneous sensor platforms for sensitive plasmonic nano-sensors.

Fabrication and characterization of shape memory polymers based bioabsorbable biomedical drug eluting stent.

Present investigation deals with, tacrolimus eluting, self-expandable, biodegradable stent fabricated by solvent casting method. The design was based on shape memory polymers, which possess the ability to memorize temporary shape that can substantially differ from their initial permanent shape. A set of biodegradable polymers blend was used such as poly-lactic acid (PLA) and poly-l-glycolic acid (PLGA) to study the shape memory effect of polymer. The prepared stent was assessed for various parameters like Scanning Electron Microscopy (SEM), In-vitro and Ex vivo expansion, Drug content, In-vitro drug release, Haemocompatibility, Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectroscopy (FTIR), and Textural Characterization.

Optimization of desolvation process for fabrication of lactoferrin nanoparticles using quality by design approach.

The present work deals with the design and process optimization for preparation of lactoferrin nanoparticles as carrier for delivery of curcumin (CLf-NPs) using quality by design (QbD) approach. Desolvation technique was selected for preparation of Lf-NPs. The concept of QbD was followed in stepwise manner including risk analysis FMEA methodology. Plackett-Burman screening design employing eight factors and two levels was selected for screening study and custom design was selected for further analysis. Curcumin was used as model polyphenol for assessing the encapsulating efficiency of Lf-NPs.

Fabrication and characterization of graphene-based hybrid nanocomposite: assessment of antibacterial potential and biomedical application.

The present investigation deals with synthesis of graphene oxide (GO) and fabrication of GO-based hybrid nanocomposites (Ncs). Synthesized GO and Ncs were primarily confirmed by UV visible and Fourier transform infrared (FT-IR) spectroscopy. Fabricated Ncs showed potential antimicrobial activity against Gram-positive and Gram-negative bacterial strains. Surface morphology, Elemental analysis, and FTIR imaging analysis were carried out to confirm Ncs formation. The Ncs were impregnated into the pullulan polymeric layer-by-layer (LbL) ultrathin film by using novel spin-coating approach. Mechanical properties were determined using Brookfield texture analyzer, and percentage moisture content confirmed the physicochemical stability of LbL film.

Nanostructured lipid carriers as a potential vehicle for Carvedilol delivery: Application of factorial design approach.

Present invention relates to design of nanostructured lipid carriers (NLC) to augment oral bioavailability of Carvedilol (CAR). In this attempt, formulations of CAR-NLCs were prepared with glyceryl-monostearate (GMS) as a lipid, poloxamer 188 as a surfactant and tween 80 as a co-surfactant using high pressure homogenizer by 2(3) factorial design approach. Formed CAR-NLCs were assessed for various performance parameters. Accelerated stability studies demonstrated negligible change in particle size and entrapment efficiency, after storage at specified time up to 3 months. The promising findings in this investigation suggest the practicability of these systems for enhancement of bioavailability of drugs like CAR.

Recent advancement in discovery and development of natural product combretastatin-inspired anticancer agents.

The natural stilbenoids combretastatin A-4 (CA4) and combretastatin A-1 (CA1) are potent antitubulin agents demonstrating antimitotic activity as well as tumor vascular disruption property. Due to structural simplicity and potent cytotoxicity of CA4 and CA1, they are considered as promising leads for the development of potent anticancer agents. In fact, scientific fraternity is motivated to synthesize several derivatives of CA4 and CA1 as novel therapeutic agents. In the literature, several studies have been carried out to evaluate the medicinal chemistry, pharmacology and structure-activity relationships (SAR) of a variety of modified combretastatin derivatives. The present report aimed at comprehensively revising the recent advancements (2006-2014) in the medicinal chemistry and SAR of diversified combretastatin analogues. The published data concerning new combretastatin A-4 analogues as antimitotic anticancer agents are presented and SAR is reviewed and discussed.

Sonication-assisted drug encapsulation in layer-by-layer self-assembled gelatin-poly (styrenesulfonate) polyelectrolyte nanocapsules: process optimization.

We report the development of Layer-by-Layer (LbL) polyelectrolyte self-assembled nanocrystalline drug-delivery platform using two experimental factors, namely the number of coatings and temperature during deposition with three varying levels. The optimized formulation (Fopt) was assessed for zeta potential and particle size using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Charge reversal along with an increase in particle size confirmed coating of polyelectrolyte on drug nanocrystals. The FT-IR study revealed no signs of incompatibility or change in formulation property during preformulation and stability study. This fact was further supported by DSC results.

Animal models for Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease with major impacts on patients' lives and on society as a whole. It is one of the most common neurodegenerative diseases in the world, second only to Alzheimer's disease. Low levels of production of dopamine (DA) are associated with PD. This is caused by a progressive loss of neurons in the midbrain's substantia nigra, resulting in changes in neural conduction within the nigrostriatum. Research into PD has been going on since 1960, still there is no cure although the symptoms can be effectively controlled and the severity of the affliction can be reduced. The main obstacle in the development of neuroprotective therapy is a limited understanding of the key molecular events that provoke neurodegeneration. A misfolding of proteins and dysfunction of the ubiquitin-proteasome pathway are the critical factors in the pathogenesis of PD. Neurotoxic models (particularly 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine) have been very useful in elucidating the molecular cascade of cell death in dopaminergic neurons. They are also of use in efforts to limit the progression of the disease and to prevent the long-term functional and pathological outcome in PD. The establishment of animal and cellular models of mutations in LRRK2 and α-synuclein, and mutations in parkin, DJ-1 and PINK1, has been of use in elucidating the molecular mechanisms of this disorder, and research using these models is providing new ideas about the pathogenesis of PD. Several researchers are synthesizing and screening novel derivatives for their antiparkinsonian potential using different animal models. In this work we describe different animal models used in assessing the antiparkinson activity of novel therapeutic treatments.

Nanoarchitectonics in cancer therapy and imaging diagnosis.

Nanoarchitectonics has gained remarkable importance due to the fabrication of various recent nanostructures with the capability of being used in biomedical science, particularly in cancer diagnosis and treatment. These nanosized structures possess unique physical and optical properties that can be exploited for cancer therapeutics, and so nanoarchitectonics is popularly known as nanomedicine. The goal of this review is to discuss the latest findings in nanostructures research including nanocrystals, nanotubes, nanoshells, nanopillars, nanoballs, nanoflowers, nanorods, nanocontainers, nanobelts, nanocages, nanodiscs, nanodots, nanoprisms, nanoplates, nanorings, nanocubes, nanobranches, nanospheres, nanorattles, nanostars, nanotrees, nanowires, nanowalls, nanodiamonds, nanosheets, layered nanostructures, quantum dots, mesoporous nanostructures etc. in the field of cancer therapy and imaging. This review further highlights brief information about use of radionuclide in cancer. Lastly, different nanoformulations that are available in the market or are under clinical trials for cancer therapy and imaging are discussed.

Graphene oxide based magnetic nanocomposites for efficient treatment of breast cancer.

The present work reports a simple one step synthesis of nanoscale graphene oxide magnetic composites (GO-IO) using ferrofluid (GO-IOF). The obtained GO-IO were compared with GO-IO obtained from in situ (GO-IOI) methods. Anastrozole (ANS) was loaded on the GO-IOI and GO-IOF via simple stirring method to form GO-IOA and GO-IOFA respectively. These GO-IO prepared by two techniques were characterized using spectroscopic techniques and vibrating sample magnetometer (VSM) analysis. Particle size and potential were measured using Malvern Zetasizer. Scanning electron microscopy (SEM) was used for studying the surface morphology of GO-IO, and in addition to this elemental analysis was also performed for confirming the presence of iron. The cell viability assay was carried out using the MCF-7 cell line. It revealed that GO-IOFA had reasonably high cytotoxicity (49.7%) compared to GO (13.1%), ANS (16.6), GO-IOI (13%), GO-IOF (13.6) and GO-IOIA (18.34%). Both, GO-IOIA and GO-IOFA showed improved cytotoxicity when compared with pure ANS. GO-IOF were found to exhibit superior magnetic activity due to higher iron content along with smaller particle size and higher loading efficiency compared to GO-IOI. The overall effect suggests that GO-IO can be utilized as efficient carriers for the loading of chemotherapeutic agents.

A comprehensive review on synthesis and designing aspects of coumarin derivatives as monoamine oxidase inhibitors for depression and Alzheimer's disease.

Monoamine oxidase (MAO) enzyme inhibition is a crucial target for the management of depression and Alzheimer disease and inhibitors of MAO are the most important drugs for their management. Coumarins are a large family of compounds, of natural and synthetic origin, that exhibit a variety of pharmacological activities, including MAO inhibition. The current review highlights the design and synthetic methods of coumarin derivatives as well as coumarins obtained from plant source as MAO inhibitors for treatment of depression and Alzheimer disease with salient finding related to structure-activity relationship. The aim of present review is to find out natural as well as synthetic coumarins as MAO inhibitors.