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1.
ACS Appl Bio Mater ; 7(1): 485-497, 2024 01 15.
Article in English | MEDLINE | ID: mdl-38165836

ABSTRACT

This study devised a label-free electrochemical immunosensor for the quantitative detection of alpha-fetoprotein (AFP). 3-Polythiophene acetic acid (3-PTAA) nanoparticles were anchored onto a few-layer graphene (FLG) nanosheet, and the resulting nanocomposite was utilized as the immunosensor platform. The AFP antibody (anti-AFP) was immobilized on 3-PTAA@FLG via a covalent interaction between the amine group of anti-AFP and the carboxylic group of 3-PTAA via ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling. FLG is largely responsible for providing electrochemical signals, whereas 3-PTAA nanoparticles are well-known for their ability to be compatible with biological molecules in neutral aqueous solutions. Moreover, the carboxyl group present in 3-PTAA effectively binds anti-AFP through EDC/NHS conjugation. Owing to good dispersibility and higher surface area of 3-PTAA, it is very convenient for casting the polymer directly on the electrode substrate followed by immobilization of anti-AFP. Thus, it is feasible to regulate the activity of AFP proteins and control the spatial distribution of the immobilized anti-AFP proteins. The electrochemical sensing performance was assessed via cyclic voltammetry and electrochemical impedance spectroscopy. For an increase in the bioconjugate concentration, the results demonstrated a surge in charge-transfer resistance and a consequent decline in the current response. This approach effectively detected AFP at an extended dynamic range of 0.0001-250 ng/mL with a detection limit of 0.047 pg/mL. Furthermore, the sensing capacity of the immunosensor for AFP detection has been demonstrated to be steady in real human serum cultures. Our approach exhibits good electrochemical performance in terms of reproducibility, selectivity, and stability, which would surely impart budding applications in the clinical diagnosis of several other tumor markers.


Subject(s)
Biosensing Techniques , Graphite , Liver Neoplasms , Nanocomposites , Nanospheres , Thiophenes , Humans , Graphite/chemistry , alpha-Fetoproteins , Biomarkers, Tumor , Acetic Acid , Biosensing Techniques/methods , Reproducibility of Results , Immunoassay/methods , Polymers , Liver Neoplasms/diagnosis , Nanocomposites/chemistry
2.
J Mater Chem B ; 11(39): 9478-9495, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37740314

ABSTRACT

Asymmetric scaffolds were developed through electrospinning by utilizing biocompatible materials for effective wound healing applications. First of all, the chitosan surface was modified with decanoyl chloride and crosslinked with collagen to synthesize collagen crosslinked modified-chitosan (CG-cross-CS-g-Dc). Then, the asymmetric scaffolds were fabricated through electrospinning, where the top layer was a monoaxial nanofiber of the PCL/graphene oxide quantum dot (GOQD) nanocomposite and the bottom layer was a coaxial nanofiber having PCL in the core and the CG-cross-CS-g-Dc/GOQD nanocomposite in the shell layer. The formation of monoaxial (∼130 ± 50 nm) and coaxial (∼320 ± 40 nm) nanofibers was confirmed by transmission electron microscopy (TEM). The presence of GOQDs contributed to antioxidant and antimicrobial efficacy. These scaffolds showed substantial antibacterial activity against the common wound pathogens Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The scaffolds exhibited excellent cytocompatibility (MTT assay) and anti-inflammatory behaviour as analysed via the cytokine assay and biochemical analysis. The in vivo wound healing potential of the nanofibrous scaffolds was assessed with full-thickness excisional wounds in a rat model. The scaffolds accelerated the re-epithelialization as well as the collagen deposition, thereby facilitating the wound healing process in a very short span of time (10 days). Both in vitro and in vivo analyses thus provide a compelling argument for the use of these scaffolds as therapeutic biomaterials and their suitability for application in rapid wound regeneration and repair.

4.
ACS Biomater Sci Eng ; 7(12): 5541-5554, 2021 12 13.
Article in English | MEDLINE | ID: mdl-34802226

ABSTRACT

In this work, a novel electrochemical immunosensor based on nitrogen doped graphene quantum dot (N-GQD) and single-walled carbon nanohorns (SWCNHs) was developed for the detection of α-fetoprotein (AFP), a cancer biomarker. Thus, to fabricate the platform of the immunosensor, nanocomposite architecture was developed by decorating N-GQD on the surface of the SWCNHs. The resulting hybrid architecture (N-GQD@SWCNHs) functioned as an exceptional base for the immobilization of antibody (Anti-AFP) through carbodiimide reaction with good stability and bioactivity. The immunosensor was prepared by evenly distributing the bioconjugates (N-GQD@SWCNHs/Anti-AFP) dispersion on the surface of the glassy carbon electrode, and subsequently blocking the remaining active sites by bovine serum albumin to prevent the nonspecific adsorption. Cyclic voltammetry and electrochemical impedance spectroscopy technique was employed to investigate the assembly process of the immunosensor. Under optimal conditions, the immunosensor exhibited a broad dynamic range in between 0.001 ng/mL to 200 ng/mL and a low detection limit of 0.25 pg/mL. Furthermore, the sensor showed high selectivity, desirable stability, and reproducibility. Measurements of AFP in human serum gave outstanding recovery within 99.2% and 102.1%. Thus, this investigation and the amplification strategy exhibited a potential role of the developed nanocomposite based sensor for early clinical screening of cancer biomarkers.


Subject(s)
Biosensing Techniques , Graphite , Nanocomposites , Neoplasms , Quantum Dots , Biomarkers, Tumor , Carbon , Early Detection of Cancer , Humans , Immunoassay , Limit of Detection , Nitrogen , Reproducibility of Results
5.
Biomater Sci ; 8(17): 4665-4691, 2020 Sep 07.
Article in English | MEDLINE | ID: mdl-32760957

ABSTRACT

Polymers have a major role in the controlled delivery of pharmaceutical compounds to a targeted portion of the body. In this quest, a high priority research area is the targeted delivery of ophthalmic drugs to the interior regions of the eyes. Due to their complex anatomical/biochemical nature. This necessitates an advanced drug delivery cargo that could administer a therapeutic agent to the targeted location by evading various obstacles. The ongoing focus is to design an ophthalmic formulation by coupling it with a smart in situ forming polymeric hydrogel. These smart macromolecules have an array of unique theranostic properties and can utilize the in vivo biological parameters as a stimulus to change their macromolecular state from liquid to gel. The fast gelling hydrogel improves the corneal contact time, facilitates sustained drug release, resists the burst-out effect, and assists drug permeability to anterior regions. This review summarizes the rationale, scientific objectives, properties, and classification of the biologically important in situ hydrogels in the niche of ophthalmic drug delivery. The current trends and prospectives of the array of stimulus-responsive polymers, copolymers, and nanomaterials are discussed broadly. The crucial biointerfacial attributes with pros and cons are reviewed by investigating the effect of the nature of polymers as well as the ratio/percentage of additives and copolymers that influence the overall performance.


Subject(s)
Drug Delivery Systems , Hydrogels , Excipients , Polymers
6.
Carbohydr Polym ; 237: 116146, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32241450

ABSTRACT

The collaborative endeavor in tissue engineering is to fabricate a bio-mimetic extracellular matrix to assist tissue regeneration. Thus, a novel injectable tissue scaffold was fabricated by exploring nanotailored hyaluronic acid (nHA) and methylcellulose (MC) (nHAMC) along with pristine HA based MC scaffold (HAMC). nHA with particle size ∼22 ±â€¯5.3 nm were obtained and nHAMC displayed a honeycomb-like 3D microporous architecture. Nano-HA bestowed better gel strength, physico-rheological and biological properties than HA. It creditably reduced the high content of salt to reduce the gelation temperature of MC. The properties ameliorated with increased in-corporation of nano-HA. The addition of salt showed more prominent effect on gelation temperature of nHAMC than in HAMC; and salting-out effect was dependent on nHA/HA content. Biocompatible nHAMC assisted adequate cell adherence and proliferation with more extended protrusions with better migration rate than control. Thus, biomodulatory effect of nanotailored glycosaminoglycan could be asserted to design an efficient thermo-responsive scaffold.


Subject(s)
Biocompatible Materials , Hyaluronic Acid , Hydrogels , Methylcellulose , Tissue Scaffolds , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Erythrocytes/drug effects , Fibroblasts/drug effects , Fibroblasts/physiology , Hemolysis/drug effects , Humans , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Methylcellulose/chemistry , Methylcellulose/pharmacology , Rheology , Wound Healing/drug effects
7.
Int J Biol Macromol ; 124: 235-245, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30481535

ABSTRACT

Triblock poloxamer copolymer (PM) has been extensively utilized to deliver various ophthalmic pharmaceutical compounds. The aim of efficient ophthalmic drug delivery strategy is to attain the longer precorneal resident time and good bioavailability of drugs. In this pursuit, the influence of cellulose nanocrystals (CNC) on the in situ gelation behavior of PM and in vitro release of pilocarpine hydrochloride from the nanocomposites formulations was studied. The critical concentration of gelation of PM being 18% (wt/v) was dropped to 16.6% (wt/v) by the addition of a very low percentage of CNC. The reinforcing nature of CNC via H-bonding in the in situ nanocomposite gel also led to an increase in gel strength along with the sustained release of loaded drugs when compared with the pure PM gel. All formulations revealed that the drug release mechanism is controlled by the Fickian diffusion. Thus, the CNC has a significant effect on the gelation behavior, gel strength, and drug release kinetics of PM-CNC formulations.


Subject(s)
Cellulose/chemistry , Eye Diseases/drug therapy , Nanoparticles/chemistry , Pilocarpine/chemistry , Administration, Ophthalmic , Cellulose/therapeutic use , Drug Compounding , Drug Delivery Systems , Humans , Nanocomposites/chemistry , Nanocomposites/therapeutic use , Nanoparticles/therapeutic use , Pilocarpine/therapeutic use , Poloxamer/chemistry , Poloxamer/therapeutic use , Polymers/chemistry , Polymers/therapeutic use
8.
Org Lett ; 20(20): 6485-6489, 2018 10 19.
Article in English | MEDLINE | ID: mdl-30336678

ABSTRACT

A stereoselective, redox-neutral, Brønsted acid-catalyzed cascade Prins-type cyclization between indole and aldehyde is described to access several structurally diverse indole terpenoid scaffolds in a single step. Applying this concept, stereodivergent total syntheses of nine hapalindole-type alkaloids are accomplished. Key transformations include allylation using geometrically isomeric allylboronic acid followed by a p-toluenesulfonic acid mediated deprotection-cyclization cascade.


Subject(s)
Indole Alkaloids/chemical synthesis , Indoles/chemical synthesis , Aldehydes/chemistry , Benzenesulfonates/chemistry , Biomimetics , Boronic Acids/chemistry , Cyclization , Indoles/chemistry , Oxidation-Reduction
9.
Int J Biol Macromol ; 102: 258-265, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28390828

ABSTRACT

The effect of gellan gum on the gelation behavior and in-vitro release of a specific drug named pilocarpine hydrochloride from different ophthalmic formulations based on poloxamer 407 is examined. The mixture of 0.3wt% gellan gum and 18wt% poloxamer (PM) solutions show a considerable increase in gel strength in physiological condition. Gel dissolution rate from PM based formulation is significantly decreased due to the addition of gellan gum. FTIR spectra analysis witnesses an interaction in between OH groups of two polymers which accounts for lowering in gelation temperature of PM-gellan gum based formulations. It is also observed from the cryo-SEM study that the pore size of PM gel decreases with an addition of gellan gum and in-vitro release studies indicate that PM-gellan gum based formulation retain drug better than the PM solution alone. Therefore, the developed formulation has the potential to be utilized as an in-situ ophthalmic drug carrier.


Subject(s)
Drug Carriers/chemistry , Drug Liberation , Pilocarpine/chemistry , Poloxamer/chemistry , Polysaccharides, Bacterial/chemistry , Temperature , Administration, Ophthalmic , Chemistry, Pharmaceutical , Gels , Models, Molecular , Molecular Conformation , Pilocarpine/administration & dosage , Viscosity
10.
Biomed Mater ; 10(2): 025011, 2015 Apr 17.
Article in English | MEDLINE | ID: mdl-25886640

ABSTRACT

The proper fabrication of biomaterials, particularly for purposes like bone regeneration, is of the utmost importance for the clinical success of materials that fulfill the design criteria at bio-interfacial milieu. Building on this aspect, a polyurethane nanocomposite (PNC) was fabricated by the combination of rapeseed protein functionalized multi-walled carbon nanotubes (MWCNTs) and vegetable-oil-based hyperbranched polyurethane. Biofunctionalized MWCNTs showed incredible biocompatibility compared to pristine MWCNTs as ascertained via in vitro and in vivo studies. PNC showed enhanced MG63 cell differentiation ability compared to the control and carboxyl functionalized MWCNT-based nanocomposite, as postulated by alkaline phosphatase activity together with better cellular adhesion, spreading and proliferation. Consequently, a critical-sized fracture gap (6 mm) bridged by the sticky PNC scaffold illustrated rapid bone neoformation within 30-45 d, with 90-93% of the defect area filling up. Histopathological studies demonstrated the reorganization of the normal tibial architecture and biodegradation of the implant. The subsequent toxicological study through cytokine expression, biochemical analysis and hematological studies suggested non-immunogenic and non-toxic effects of PNCs and their degraded/leached products. Their excellent bio-physiological features with high load-bearing ability (49-55.5 Mpa), ductility (675-790%) and biodegradability promote them as the best alternative biomaterials for bone regeneration in a comprehensive manner.


Subject(s)
Bone Regeneration , Nanocomposites/chemistry , Nanotubes, Carbon/chemistry , Polyurethanes/chemistry , Absorbable Implants , Animals , Biocompatible Materials/chemistry , Biomechanical Phenomena , Cell Differentiation , Cell Line , Cell Proliferation , Fracture Healing , Male , Materials Testing , Nanocomposites/ultrastructure , Nanotubes, Carbon/ultrastructure , Osteoblasts/cytology , Radiography , Rats , Rats, Wistar , Tibial Fractures/diagnostic imaging , Tibial Fractures/pathology , Tibial Fractures/surgery , Tissue Scaffolds/chemistry
11.
Biomed Mater ; 8(3): 035003, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23532037

ABSTRACT

The fabrication of a smart magnetically controllable bio-based polymeric nanocomposite (NC) has immense potential in the biomedical domain. In this context, magneto-thermoresponsive sunflower oil modified hyperbranched polyurethane (HBPU)/Fe3O4 NCs with different wt.% of magnetic nanoparticles (Fe3O4) were prepared by an in situ polymerization technique. Fourier-transform infrared, x-ray diffraction, vibrating sample magnetometer, scanning electron microscope, transmission electron microscope, thermal analysis and differential scanning calorimetric were used to analyze various physico-chemical structural attributes of the prepared NC. The results showed good interfacial interactions between HBPU and well-dispersed superparamagnetic Fe3O4, with an average diameter of 7.65 nm. The incorporation of Fe3O4 in HBPU significantly improved the thermo-mechanical properties along with the shape-memory behavior, antibacterial activity, biocompatibility as well as biodegradability in comparison to the pristine system. The cytocompatibility of the degraded products of the NC was also verified by in vitro hemolytic activity and MTT assay. In addition, the in vivo biocompatibility and non-immunological behavior, as tested in Wistar rats after subcutaneous implantation, show promising signs for the NC to be used as antibacterial biomaterial for biomedical device and implant applications.


Subject(s)
Anti-Bacterial Agents/chemistry , Biocompatible Materials/chemistry , Magnetite Nanoparticles/chemistry , Nanocomposites/chemistry , Absorbable Implants , Animals , Bacterial Adhesion , Biomechanical Phenomena , Equipment and Supplies , Materials Testing , Molecular Structure , Polyurethanes/chemistry , Prostheses and Implants , Rats , Rats, Wistar
12.
Macromol Biosci ; 13(1): 126-39, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23212970

ABSTRACT

Hyperbranched polyurethanes are synthesized using TDI, PCL diol, butanediol, and pentaerythritol (1-5 wt%) as the B(4) reactant with and without the monoglyceride of sunflower oil. The biodegradation, physico-mechanical, and thermal properties are found to be tailored by varying the percentage weight of the branching unit. An MTT/hemolytic assay and subcutaneous implantation in Wistar rats followed by cytokine/ALP assay and histopathology studies confirm a better biocompatibility of HBPU with MG than without MG. HBPU supports the proliferation of dermatocytes with no toxic effect in major organs, in addition the in vitro degraded products are non-toxic. Cell adherence and proliferation endorse the bio-based HBPU as a prospective scaffold material in the niche of tissue engineering.


Subject(s)
Absorbable Implants , Biocompatible Materials/chemical synthesis , Polyurethanes/chemistry , Tissue Engineering , Tissue Scaffolds/chemistry , Animals , Biocompatible Materials/chemistry , Cell Adhesion , Cell Proliferation , Male , Materials Testing , Rats , Rats, Wistar , Stress, Mechanical
13.
J Mater Chem B ; 1(33): 4115-4126, 2013 Sep 07.
Article in English | MEDLINE | ID: mdl-32260964

ABSTRACT

This study focused on the design of novel mechanically tough, biocompatible, osteoconductive and biodegradable scaffolds based on sunflower oil modified hyperbranched polyurethane (HBPU)/functionalized multi-walled carbon nanotube (f-MWCNT) nanocomposites (NCs), and the response of an animal model on their post-implantation. The NC was prepared by an in situ polymerization technique with different wt% of f-MWCNTs. The tensile strength of the NCs was enhanced to 36.98-47.6 MPa from 23.93 MPa (HBPU) and toughness from 12 767 to 18 427-19 440 due to the addition and efficient dispersion of the f-MWCNTs in the HBPU matrix. The post-60 days in vitro biodegraded NC retained sufficient strength (39 ± 1.65 MPa). The increase in wt% of f-MWCNTs had a significant effect on tailoring the physico-mechanical properties of the polymer. The hematological, histological and immunological indices of toxicity suggested the safety potential of the prepared systems within the tested animal model. Moreover, the cytokines (viz. IL-6 and TNF-α) detection, MTT assay and anti-hemolytic assay boosted the non-toxic behavior of the systems. The NC with interconnected pores size (200-330 µm) showed better proliferation and adherence of osteoblast (MG63) cells compared to the HBPU and the results were comparable with the control. Thus the findings confirmed the non-toxicity of f-MWCNTs in association with the polymer and thereby endorsed the NC as a potential biomimetic scaffold for bone tissue engineering.

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