EGFR Targeted Redox Sensitive Chitosan Nanoparticles of Cabazitaxel: Dual-Targeted Cancer Therapy, Lung Distribution, and Targeting Studies by Photoacoustic and Optical Imaging.

In this research, we have modified tocopheryl polyethylene glycol succinate (TPGS) to a redox-sensitive material, denoted as TPGS-SH, and employed the same to develop dual-receptor-targeted nanoparticles of chitosan loaded with cabazitaxel (CZT). The physicochemical properties and morphological characteristics of all nanoparticle formulations were assessed. Dual-receptor targeting redox-sensitive nanoparticles of CZT (F-CTX-CZT-CS-SH-NPs) were developed by a combination of pre- and postconjugation techniques by incorporating synthesized chitosan-folate (F) and TPGS-SH during nanoparticle synthesis and further postconjugated with cetuximab (CTX) for epidermal growth factor receptor (EGFR) targeting. The in vitro release of the drug was seemingly higher in the redox-sensitive buffer media (GSH, 20 mM) compared to that in physiological buffer. However, the extent of cellular uptake of dual-targeted nanoparticles was significantly higher in A549 cells than other control nanoparticles. The IC50 values of F-CTX-CZT-CS-SH-NPs against A549 cells was 0.26 ± 0.12 µg/mL, indicating a 6.3-fold and 60-fold enhancement in cytotoxicity relative to that of dual-receptor targeted, nonredox sensitive nanoparticles and CZT clinical injection, respectively. Furthermore, F-CTX-CZT-CS-SH-NPs demonstrated improved anticancer activity in the benzo(a)pyrene lung cancer model with a higher survival rate. Due to the synergistic combination of enhanced permeability and retention (EPR) effect of small-sized nanoparticles, the innovative and redox sensitive TPGS-SH moiety and the dual folate and EGFR mediated augmented endocytosis have all together significantly enhanced their biodistribution and targeting exclusively to the lung which is evident from their ultrasound/photoacoustic and in vivo imaging system (IVIS) studies.

Superporous soy protein isolate matrices as superabsorbent dressings for successful management of highly exuding wounds: In vitro and in vivo characterization.

Soy protein isolate (SPI) has received widespread attention of the biomedical research community primarily due to its good biocompatibility, biodegradability, high availability and low cost. Herein, glutaraldehyde cross-linked microporous sponge-like SPI scaffolds were prepared using the cryogelation technique for tissue engineering applications. The prepared SPI scaffolds possess an interconnected porous structure with approximately 90% porosity and an average pore size in the range of 45-92 µm. The morphology, porosity, swelling capacity and degradation rate of the cryogels were found to be dependent on the concentration of polymer to crosslinking agent. All cryogels were found to be elastic and able to maintain physical integrity even after being compressed to one-fifth of their original length during cyclic compression analysis. These cryogels showed excellent mechanical properties, immediate water-triggered shape restoration and absorption speed. Furthermore, cryogels outperformed cotton and gauze in terms of blood clotting and blood cell adherence. The in vitro and in vivo studies demonstrated the potency of SPI scaffolds for skin tissue engineering applications. Our findings showed that crosslinking with glutaraldehyde had no detrimental effects on cell viability. In addition, an in vivo wound healing study in rats validated them as good potential wound dressing materials.

Current Advances in Nanotheranostics for Molecular Imaging and Therapy of Cardiovascular Disorders.

Cardiovascular diseases (CVDs) refer to a collection of conditions characterized by abnormalities in the cardiovascular system. They are a global problem and one of the leading causes of mortality and disability. Nanotheranostics implies to the combination of diagnostic and therapeutic capabilities inside a single nanoscale platform that has allowed for significant advancement in cardiovascular diagnosis and therapy. These advancements are being developed to improve imaging capabilities, introduce personalized therapies, and boost cardiovascular disease patient treatment outcomes. Significant progress has been achieved in the integration of imaging and therapeutic capabilities within nanocarriers. In the case of cardiovascular disease, nanoparticles provide targeted delivery of therapeutics, genetic material, photothermal, and imaging agents. Directing and monitoring the movement of these therapeutic nanoparticles may be done with pinpoint accuracy by using imaging modalities such as cardiovascular magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), photoacoustic/ultrasound, and fluorescence imaging. Recently, there has been an increasing demand of noninvasive for multimodal nanotheranostic platforms. In these platforms, various imaging technologies such as optical and magnetic resonance are integrated into a single nanoparticle. This platform helps in acquiring more accurate descriptions of cardiovascular diseases and provides clues for accurate diagnosis. Advances in surface functionalization methods have strengthened the potential application of nanotheranostics in cardiovascular diagnosis and therapy. In this Review, we have covered the potential impact of nanomedicine on CVDs. Additionally, we have discussed the recently developed various nanoparticles for CVDs imaging. Moreover, advancements in the CMR, CT, PET, ultrasound, and photoacoustic imaging for the CVDs have been discussed. We have limited our discussion to nanomaterials based clinical trials for CVDs and their patents.

EGFR targeted albumin nanoparticles of oleanolic acid: In silico screening of nanocarrier, cytotoxicity and pharmacokinetics for lung cancer therapy.

This study aimed to develop cetuximab (CTX) functionalized albumin nanoparticles (ALB-NPs) of oleanolic acid for EGFR targeted lung cancer therapy. The molecular docking methodology has been applied for a selection of suitable nanocarrier. Various physicochemical parameters like particle size, polydispersity, zeta potential, morphology, entrapment efficiency, and in-vitro drug release of all the ALB-NPs were analyzed. Furthermore, the in-vitro qualitative and quantitative cellular uptake study revealed that higher uptake of CTX conjugated ALB-NPs than nontargeted ALB-NPs in A549 cells. The in-vitro MTT assay revealed that the IC50 value of CTX-OLA-ALB-NPs (4.34 ± 1.90 µg/mL) was significantly reduced (p < 0.001) than OLA-ALB-NPs (13.87 ± 1.28 µg/mL) in A-549 cells. CTX-OLA-ALB-NPs caused apoptosis in A-549 cells at concentrations equivalent to its IC50 value and blocked the cell cycle in the G0/G1 phases. The hemocompatibility, histopathology and lung safety study confirmed the biocompatibility of the developed NPs. In vivo ultrasound and photoacoustic imaging confirmed the targeted delivery of the NPs to lung cancer. The findings demonstrated that CTX-OLA-ALB-NPs have potential for site-specific delivery of OLA for effective and targeted therapy of lung carcinoma.

Assessment of various forms of cellulose-based Luffa cylindrica (mat, flakes and powder) reinforced polydimethylsiloxane composites for oil sorption and organic solvents absorption.

Oil spillage has damaged public health noticeably and contributed to significant environmental deterioration. As a result, a significant amount of effort has been spent on investigating and developing the sorbent materials capable of separating oil from water. Thus, the sorbent materials that could be effective particularly in oil spill disposal and resolve such environmental issue remain to be explored. We have proposed luffa cylindrica (LC)-polydimethylsiloxane (PDMS) composite forms to remove the oil and organic components that might be hazardous to aquatic organisms. The scaffolds were fabricated using hand lay-up method with various forms of luffa cylindrica i.e., LC mat, flakes and powder. Various characterizations such as scanning electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA), effective porosity, surface wettability, mechanical stability, cytotoxicity and sorption behavior with respect to oil, phosphate buffer saline (PBS) and few organic solvents were performed. The results showed that the scaffold in combination with P-L flakes was highly effective in eradicating oil spills and removing harmful components of crude oil. Scaffolds composed of P-L mat, P-L flakes, P-L powder, and PDMS (P) exhibited oil absorption efficacy around 16.09 ± 4.62 %, 24.49 ± 3.55 %, 15.52 ± 2.67 % and 5.52 ± 1.44 %, respectively. We anticipate that the proposed scaffolds have the tremendous potential to provide a solution to this significant environmental remediation issue and to serve as a cost-effective method for removing oil spills and hazardous crude oil components.

Regenerative Potential of Human Breast Milk: A Natural Reservoir of Nutrients, Bioactive Components and Stem cells.

Human milk is a complex fluid that contains carbohydrates, lipids, proteins, and other bioactive molecules (immunoglobulins, lactoferrin, human milk oligosaccharides, lysozyme, leukocytes, cytokines, hormones, and microbiome) which provide nutritional, immunological, and developmental benefits to the infant. In addition to their involvement in the development, these bioactive compounds have a key role in anti-oncogenicity, neuro-cognitive development, cellular communication, and differentiation. As a result of technological advancements, it has been discovered that human breast milk contains cells that display many of the characteristics of stem cells with multilineage differentiation potentials. Do these cells have any specific properties or roles? Research efforts on breast milk cells have been mainly focused on leukocytes based on their immunological perspective in the early postpartum period. This review summarizes the nutritional components in human milk, i.e., the macro and micronutrients required for the growth and development of infants. Further, it discusses the research work reported concerning the purification, propagation, and differentiation of breast milk progenitor cells and highlights the advancements made in this newly emerging field of stem cell biology and regenerative medicine.

GPIIb/IIIa Receptor Targeted Rutin Loaded Liposomes for Site-Specific Antithrombotic Effect.

Rutin (RUT) is a flavonoid obtained from a natural source and is reported for antithrombotic potential, but its delivery remains challenging because of its poor solubility and bioavailability. In this research, we have fabricated novel rutin loaded liposomes (RUT-LIPO, nontargeted), liposomes conjugated with RGD peptide (RGD-RUT-LIPO, targeted), and abciximab (ABX-RUT-LIPO, targeted) by ethanol injection method. The particle size, ζ potential, and morphology of prepared liposomes were analyzed by using DLS, SEM, and TEM techniques. The conjugation of targeting moiety on the surface of targeted liposomes was confirmed by XPS analysis and Bradford assay. In vitro assessment such as blood clot assay, aPTT assay, PT assay, and platelet aggregation analysis was performed using human blood which showed the superior antithrombotic potential of ABX-RUT-LIPO and RGD-RUT-LIPO liposomes. The clot targeting efficiency was evaluated by in vitro imaging and confocal laser scanning microscopy. A significant (P < 0.05) rise in the affinity of targeted liposomes toward activated platelets was demonstrated that revealed their remarkable potential in inhibiting thrombus formation. Furthermore, an in vivo study executed on Sprague Dawley rats (FeCl3 model) demonstrated improved antithrombotic activity of RGD-RUT-LIPO and ABX-RUT-LIPO compared with pure drug. The pharmacokinetic study performed on rats demonstrates the increase in bioavailability when administered as liposomal formulation as compared to RUT. Moreover, the tail bleeding assay and clotting time study (Swiss Albino mice) indicated a better antithrombotic efficacy of targeted liposomes than control preparations. Additionally, biocompatibility of liposomal formulations was determined by an in vitro hemolysis study and cytotoxicity assay, which showed that they were hemocompatible and safe for human use. A histopathology study on rats suggested no severe toxicity of prepared liposomal formulations. Thus, RUT encapsulated nontargeted and targeted liposomes exhibited superior antithrombotic potential over RUT and could be used as a promising carrier for future use.

Effects of ELF-PEMF exposure on spontaneous alternation, anxiety, motor co-ordination and locomotor activity of adult wistar rats and viability of C6 (Glial) cells in culture.

The effects of ELF-PEMF exposure on spontaneous alternation, anxiety, motor coordination, and locomotor activity have been discussed in various pre-clinical and clinical settings. Several epidemiological and experimental studies have demonstrated the potential effects of ELF-PEMF when exposed > âˆ¼1 h/day; however, very few studies have focused on understanding the influence of ELF-PEMF exposure of 1-3 mT with an exposure duration of < 1 h/day on spontaneous alternation, anxiety, motor coordination, and locomotor activity. Hence, we attempted to study the effects of ELF-PEMF exposure of 1-3 mT, 50 Hz with an exposure duration of 20 min each with a 4 h gap (2 times) on the cellular proliferation and morphologies of C6 (Glial) cells and spontaneous alternation, anxiety, motor coordination and locomotor activity of Wistar rats under in vitro and in vivo conditions, respectively. The results showed that ELF-PEMF exposure did not induce any significant levels of cellular fragmentation and changes in the morphology of glial cells. Also, the outcomes revealed no noticeable effects on spontaneous alternation, anxiety, motor coordination, and locomotor activity in PEMF-exposed groups compared with the control. No undesirable side effects were observed at the highest dose (B=3 mT). We also performed histological analysis of the selected brain sections (hippocampus and cortex) following ELF-PEMF exposure. Incidentally, no significant changes were observed in cortical cell counts, tissue structure, and morphology.

Chitosan-alginate nanoparticles of cabazitaxel: Design, dual-receptor targeting and efficacy in lung cancer model.

Cabazitaxel (CZT) loaded chitosan-alginate based (CSA) nanoparticles were developed with dual targeting functions of both folate receptor and epidermal growth factor receptor (EGFR) using ionic gelation technique. The chitosan-folate conjugate was synthesized, and characterized by using FTIR, NMR and Mass spectroscopy. The physicochemical parameters and morphology of all CSA nanoparticles were examined. The degree of conjugation of folic acid and cetuximab (CTXmab) was determined by UV-Visible spectroscopy and Bradford assay, respectively. Moreover, XPS analysis also supported the presence of the ligands on nanoparticles. The cellular-uptake study performed on A-549 cells demonstrated a significant enhancement in the uptake of dual-receptor targeted CSA nanoparticles than non-targeted and single-receptor targeted CSA nanoparticles. Further, CZT-loaded dual receptors targeted CSA nanoparticles also showed significantly lower IC50 values (~38 folds) than the CZT control against A-549 cells. Further, in-vivo histopathological evaluations of dual receptor-targeted CSA nanoparticles have demonstrated better safety in Wistar rats. Moreover, its treatment on the Benzo(a)pyrene (B(a)P) induced lung cancer mice model has showed the enhanced anticancer efficacy of CZT with a prolonged survival rate.

Fabrication and in vitro characterization of luffa-based composite scaffolds incorporated with gelatin, hydroxyapatite and psyllium husk for bone tissue engineering.

Bone tissue engineering is an emerging technology that has been developed in recent years to address bone abnormalities by repairing, regenerating and replacing damaged/injured tissues. In present work, we report the fabrication and characterization of porous luffa-based composite scaffolds composed of Luffa cylindrica (sponge gourd) powder (LC)/hydroxyapatite (HA), psyllium husk (PH) and gelatin (G) in various combinations (w/v) i.e. 3% LC, 5% LC and control (C) (without luffa powder) by using freeze-drying method. The structural stability of the scaffolds was obtained after chemically crosslinking them with glutaraldehyde (GTA), which was identified via scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The hydrophilic behavior of the samples was quantified by water contact angle measurements. The average pore size of the scaffolds was observed in a range of 20-240 µm. As per the obtained data, the apparent and effective porosities were estimated as ∼57.08 ± 4.38%, ∼50.58 ± 4.09%, ∼59.45 ± 1.60% and 51.37 ± 3.36%, 47.94 ± 4.57% and 53.09 ± 5.45% for 3% LC, 5% LC and control (C) scaffolds, respectively. The scaffolds were found to be noticeably stable for 50 days at 37 °C in a lysozyme solution. The liquid retention capacity of the scaffolds revealed that the luffa-based scaffolds gained lower retention capacity compared to the control (C) scaffold; indicating an increase in scaffold stiffness due to the addition of luffa. Compressive strength study demonstrated that the mechanical stability of the fabricated luffa-based scaffolds got increased significantly from ∼1.5 to ∼9.5 MPa, which is comparable to that of trabecular bone. In addition, proliferation and viability analysis of MG-63 osteoblast-like cells revealed a significant level of cellular compatibility i.e. approaching ∼64% proliferation by 6th day in vitro compared to control. Thus, the obtained results demonstrate that the fabricated novel luffa-based scaffolds exhibit good cytocompatibility, remarkable porosity and excellent mechanical strength comparable to native human bone. Therefore, we anticipate that the developed luffa-based scaffolds could be a promising candidate for bone tissue engineering applications.

Freeze-Thaw-Induced Physically Cross-linked Superabsorbent Polyvinyl Alcohol/Soy Protein Isolate Hydrogels for Skin Wound Dressing: In Vitro and In Vivo Characterization.

In this work, polyvinyl alcohol (PVA)- and soy protein isolate (SPI)-based scaffolds were prepared by physical cross-linking using the freeze-thaw method. The PVA/SPI ratio was varied to examine the individual effects of the two constituents. The physicochemical properties of the fabricated scaffolds were analyzed through Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, and differential scanning calorimetry. The SPI concentration significantly affected the properties of scaffolds, such as the extent of gelation (%), pore size, porosity, degradation, swelling, and surface wettability. The in vitro degradation of fabricated hydrogels was evaluated in phosphate-buffered saline and lysozyme solution for a duration of 14 days. The in vitro compatibility of prepared hydrogels was evaluated by the MTT assay with NIH-3T3 cells (fibroblast). The water vapor transmission rate (WVTR) assays showed that all hydrogels possessed WVTR values in the range of 2000-2500 g m-2 day-1, which is generally recommended for ideal wound dressing. Overall, the obtained results reveal that the fabricated scaffolds have excellent biocompatibility, mechanical strength, porosity, stability, and degradation rate and thus carry enormous potential for tissue engineering applications. Furthermore, a full-thickness wound healing study performed in rats supported them as a promising wound dressing material.

Revisiting Methodologies for In Vitro Preparations of Advanced Glycation End Products.

Chronic elevation of sugar and oxidative stress generally results in development of advanced glycation end products (AGEs) in diabetic individuals. Accumulation of AGEs in an individual can give rise to the activation of several pathways that will ultimately lead to various complications. Such AGEs can also be prepared in an in vitro environment. For an in vitro preparation of advanced glycation end products (AGEs), proteins, lipids, or nucleic acids are generally required to be incubated with reducing sugars at a physiological temperature or higher depending upon the protocol optimized for its preparation. Certain other factors are also optimized and added to the buffer to hasten its preparation or alter the properties of prepared AGEs. Through this review, we intend to highlight the various studies related to the experimental procedures for the preparation of different types of AGEs. In addition, we present the comparative study of methodologies optimized for the preparation of AGEs.

Bioadhesive chitosan nanoparticles: Dual targeting and pharmacokinetic aspects for advanced lung cancer treatment.

The chitosan-folate conjugate was synthesized initially and confirmed by FTIR and NMR spectroscopic studies. Following, docetaxel (DXL) loaded non-targeted, single receptor and dual receptor (folate and EGFR) targeted chitosan nanoparticles were prepared and their shape, particle size, zeta-potential, surface morphology and texture were screened by SEM, TEM, AFM analyses. Surface chemistry analysis by XPS indeed confirmed the successful conjugation of folate and cetuximab on the targeted formulations. In-vitro analysis of dual-targeted chitosan nanoparticles has revealed their superior cytotoxicity against A-549 cells. The IC50 of dual receptor-targeted chitosan NP was almost 34 times lower than DXL control. In-vivo pharmacokinetic study on Wistar rats has demonstrated improved relative bioavailability of all NP in comparison to DXL control. The results illustrated that EGFR and folate dual targeted NP enhanced the cytotoxicity of DXL towards A-549 lung cancer cells and substantially improved DXL pharmacokinetics in rats.

High-manganese and nitrogen stabilized austenitic stainless steel (Fe-18Cr-22Mn-0.65N): a material with a bright future for orthopedic implant devices.

The rationale behind the success of nickel free or with extremely low nickel austenitic high manganese and nitrogen stabilized stainless steels is adverse influences of nickel ion on human body. Replacement of nickel by nitrogen and manganese provides a stable microstructure and facilitates better biocompatibility in respect of the conventional 316L austenitic stainless steel (316L SS). In this investigation, biocompatibility of the high-manganese and nitrogen stabilized (Fe-18Cr-22Mn-0.65N) austenitic stainless steel was studied and found highly promising.In vitrocell culture and cell proliferation (MTT) assays were performed on this stainless steel and assessed in respect of the 316L SS. Both the steels exhibited similar cell growth behavior. Furthermore, an enhancement was observed in cell proliferation on the Fe-18Cr-22Mn-0.65N SS after surface modification by ultrasonic shot peening (USP). The mean percent proliferation of the MG-63 cells increased from ≈88% for Un-USP to 98% and 105% for USP 3-2 and USP 2-2 samples, respectively for 5 d of incubation. Interestingly,in vivoanimal study performed in rabbits for 3 and 6 weeks showed callus formation and sign of union without any allergic reaction.

Fabrication and Characterization of Silk Fibroin-Based Nanofibrous Scaffolds Supplemented with Gelatin for Corneal Tissue Engineering.

Tissue engineering is a promising approach to overcome the severe worldwide shortage of healthy donor corneas. In this work, we have developed a silk-gelatin composite scaffold using electrospinning and permeation techniques to achieve the properties comparable to cornea analog. In particular, we present the fabrication and comparative evaluation of the novel gelatin sheets consisting of silk fibroin nanofibers, which are prepared using silk fibroin (SF) (in formic acid) and SF (in aqueous) electrospun scaffolds, for its suitability as corneal stromal analogs. All the fabricated samples were treated with ethanol vapor (T) to physically crosslink the silk nanofibers. Micro/nano-scale features of the fabricated scaffolds were analyzed using scanning electron microscopy micrographs. Fourier transform infrared spectroscopy revealed characteristic peaks of polymeric functional groups and modifications upon ethanol vapor treatment. Transparency of the scaffolds was determined using UV-visible spectra. Among all the fabricated samples, the gelatin-permeated SF (in formic acid; T) scaffold showed the highest level of transparency, i.e., 77.75 ± 2.3%, which is similar to that of the native cornea (∼70%-90% [variable with age group]) with healthy acute vision. Contact angle of the samples was studied to estimate the hydrophilicity of the scaffolds. All the scaffolds except non-treated SF (in aqueous; NT) were found to be significantly stable up to 14 days when incubated in phosphate buffered saline at 37°C. Treated samples showed significantly better stability, both physically and microscopically, in comparison to nontreated samples. Proliferation and viability assays of rabbit corneal fibroblast cells (SIRC) and mouse fibroblast cells (L929 RFP) when cultured on fabricated scaffolds revealed remarkable cellular compatibility with gelatin-permeated SF (in formic acid; T) scaffolds compared to SF (in aqueous; T). Unlike other reports in the existing literature, this work presents the design and development of a nanofibrous silk-gelatin composite that exhibits acceptable transparency, cellular biocompatibility, as well as improved mechanical stability comparable to that of native cornea. Therefore, we anticipate that the fabricated novel scaffold is likely to be a good candidate for corneal tissue construct. Moreover, among the fabricated scaffolds, the outcomes depict gelatin-permeated SF (in formic acid; T) composite scaffold to be a better candidate as a corneal stromal analog that carries properties of both the silk and gelatin, i.e., optimal transparency, better stability, and enhanced cytocompatibility.

Novel redox-sensitive thiolated TPGS based nanoparticles for EGFR targeted lung cancer therapy.

Novel glutathione (GSH) redox-sensitive thiolated vitaminE-PEG1000-succinate (TPGH-SH) was synthesized by conjugating TPGS with 4-amino thiophenol (4-ATP) and confirmed by FTIR and NMR studies. Following, docetaxel (DTX) loaded, cetuximab (CTB) conjugated redox sensitive TPGS-SH nanoparticles (TPGS-SH NP) were prepared by dialysis method and screened for size, charge, DTX entrapment, which revealed that size, surface charge and percent entrapment are in the range of 183-227 nm, +18 to +26 mV and 68-71%. SEM, TEM, AFM have reflected the spherical and uniform size of NP with a smooth surface. In-vitro release studies were performed in media containing different concentrations of GSH to study their effect on drug release and drug release of up to 94.5%, at pH 5.5, GSH 20 mM, is observed within 24 h. The pH/redox sensitivity studies revealed the better stability of NP at higher pH and lower GSH concentrations. In-vitro cytotoxicity, cellular uptake, migration and apoptotic assays, performed on A549 cells, have proved that targeted formulation produced higher cytotoxicity (significantly less IC50 value) and uptake and also prevented cell migration. Pharmacokinetic and histopathological screening were performed on CF rats, which demonstrated promising results. The in-vivo efficacy studies on benzo(a)pyrene induced mice lung cancer model showed that targeted TPGS-SH NP has significantly reduced the cell number than the model control.

Aluminium Oxide Thin-Film Based In Vitro Cell-Substrate Sensing Device for Monitoring Proliferation of Myoblast Cells.

We demonstrate cell-substrate interaction on aluminium oxide thin-film in metal-insulator-metal structure followed by the change in dielectric characteristics of Al2O3 as a function of progression of cellular growth. The theoretical calculation of the fabricated biosensor reveals that the changes in the intrinsic elemental parameters are mainly attributed to the cell-induced behavioural changes.

Functional Behavior of the Primary Cortical Neuronal Cells on the Large Surface of TiO2 and SnO2 Based Biosensing Device.

In this study, we report the fabrication of poly-L-lysine (PLL) coated large surface TiO2 and SnO2 based biosensing devices to analyze the influence of the functional behaviour of primary cortical neuronal cells. Through frequency-dependent impedance study, we observed an increase in the impedance values initially most likely due to cell adhesion, proliferation and differentiation processes leading to an increase in both the single-cell mass as well as overall cellular mass; however, it got decreased eventually with the progression of various other cellular functions including neural activity, synapse formation and neuron-neuron communication. Typically, formation and regulation of the neuronal junction i.e., synapses noticeably affected the functional behaviour of the fabricated biosensing device by increasing the neuronal communication and thereby improving the flow of current by altering the thin film resistance and capacitance. Further, the neuro-electrical phenomenon is validated by fitting the experimental impedance data to an equivalent electrical circuit model. A significant shift in the Nyquist plot was also observed visually, which indicates that this alternation is primarily due to change in characteristic behaviour of the fabricated biosensing device. Hence, we anticipate that the fabricated PLL coated large surface TiO2 and SnO2 based biosensing device can serve as a promising tool to monitor the influence of the functional behaviour of neuronal cells.

Printability assessment of psyllium husk (isabgol)/gelatin blends using rheological and mechanical properties.

The primary goal of this study is to highlight the rheological and mechanical properties of a new blend composed of naturally-derived hydrogel materials- psyllium husk (PH) and gelatin (G) for its potential use in three-dimensional (3D) printing technology. The mixtures were prepared at various weight ratios of 100PH, 75PH + 25G and 50PH + 50G. A suitable selection of the printable ink was made based on the preliminary screening steps of manual filament drop test and layer stacking by 3D printing. Printing of the common features such as hexagon and square grids helped evaluating shape fidelity of the chosen ink. Although 50PH + 50G blend was found meeting most of the criteria for an ideal 3D printable ink, rheological and mechanical characterizations have been performed for all the ratios of polymeric blends. This study documents the correlation between various factors of rheology that should be taken into account while categorizing any biomaterial as a printable ink. Yield stress was measured as 18.59 ± 4.21 Pa, 268.74 ± 13.56 Pa and 109.16 ± 9.85 Pa for 50PH + 50G, 75PH + 25G and 100PH, respectively. Similarly, consistency index (K) and flow index (n) were calculated using the power law equation and found as 49.303 ± 4.17, 530.59 ± 10.92, 291.82 ± 10.53 and 0.275 ± 0.04, 0.05 ± 0.005, 0.284 ± 0.04 for 50PH + 50G, 75PH + 25G and 100PH, respectively. The loss modulus (G″) was observed dominating over storage modulus (G') for 50PH + 50G, that depicts its liquid-like property; whereas storage modulus (G') was found dominating in case of 75PH + 25G and 100PH, indicating their solid-like characteristics. In addition, the loss tangent value (tan δ) of 50PH + 50G was observed exceeding unity (1.05), supporting its plastic behavior, unlike 75PH + 25G (0.5) and 100PH (0.33) whose loss tangent values were estimated less than unity revealing their elastic behavior. Also, 50PH + 50G was found to have the highest mechanical strength amongst the three blends with a Young's modulus of 9.170 ± 0.0881 kPa.

Formulation and in vivo efficacy study of cetuximab decorated targeted bioadhesive nanomedicine for non-small-cell lung cancer therapy.

Aim: To design, optimize and evaluate docetaxel-loaded chitosan nanoparticles with (targeted) and without (nontargeted) cetuximab conjugation for the treatment of non-small-cell lung cancer (NSCLC). Materials & methods: Risk-assessment, optimization, in vitro characterizations, stability assessments, release studies, cell-culture studies were performed along with histopathology, pharmacokinetic and anticancer efficacy studies. Results: The nanoparticles of desired particle size (152.59 ± 3.90 nm to 180.63 ± 5.21 nm) which could sustain drug release for up to 70 h, were obtained. The cell-culture studies demonstrated the superiority of the formulations over Docel™. The pharmacokinetic evaluation showed the excellent systemic bioavailability of prepared NPs. The histopathology screening revealed lesser toxicity of both the nontargeted and targeted formulations. The targeted nanoformulation significantly reduced tumor growth than the nontargeted formulation and Docel. Conclusion: These results demonstrate the therapeutic potential of the prepared nanoformulation. After proper clinical validation, it could be a promising approach for the treatment of NSCLC.