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1.
Biomacromolecules ; 21(9): 3782-3794, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32701262

RESUMO

Acceleration of gelation in the biological environment and improvement of overall biological properties of a hydrogel is of enormous importance. Biopolymer stabilized gold (Au) nanoparticles (NPs) exhibit cytocompatibility and therapeutic activity. Hence, in situ gelation and subsequent improvement in the property of a hydrogel by employing Au NPs is an attractive approach. We report that stable Au NPs accelerate the conventional nucleophilic substitution reaction of activated halide-terminated poly(ethylene glycol) and tertiary amine functional macromolecules, leading to the rapid formation of injectable nanocomposite hydrogels in vivo and ex vivo with improved modulus, cell adhesion, cell proliferation, and cytocompatibility than that of a pristine hydrogel. NP surfaces with low chain grafting density and good colloidal stability are crucial requirements for the use of these NPs in the hydrogel formation. Influence of the structure of the amine functional prepolymer, the spacer connecting the halide leaving groups of the substrate, and the structure of the stabilizer on the rate promoting activity of the NPs have been evaluated with model low-molecular-weight substrates and macromolecules by 1H NMR spectroscopy, rheological experiments, and density functional theory. Results indicate a significant effect of the spacer connecting the halide leaving group with the macromolecule. The Au nanocomposite hydrogels show sustained co-release of methotrexate, an anti-rheumatic drug, and the Au NPs. This work provides insights for designing an injectable nanocomposite hydrogel system with multifunctional property. The strategy of the use of cytocompatible Au NPs as a promoter provides new opportunity to obtain an injectable hydrogel system for biological applications.


Assuntos
Hidrogéis , Nanopartículas Metálicas , Ouro , Substâncias Macromoleculares , Polietilenoglicóis
2.
Langmuir ; 35(38): 12285-12305, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31125238

RESUMO

This feature article provides an overview of different kinds of futuristic biomaterials which have the potential to be used for fluorescent imaging and drug delivery, often simultaneously. The synthesis route or preparation process, fluorescence property, release profile, biocompatibility, bioimaging, and mechanistic approaches are vividly discussed. These include bioimaging with fluorescently doped quantum dots, mesoporous silica, noble metals, metal clusters, hydrophilic/hydrophobic polymers, semiconducting polymer dots, carbon/graphene dots, dendrimers, fluorescent proteins, and other nanobiomaterials. Another section discusses the controlled and targeted drug, gene, or biologically active material delivery using various vehicles such as micelles, 2D nanomaterials, organic nanoparticles, polymeric nanohybrids, and chemically modified polymers. In the last section, we discuss biomaterials, which can deliver biologically active molecules, and imaging the cell/tissue.


Assuntos
Materiais Biocompatíveis , Portadores de Fármacos , Imagem Molecular/métodos , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Humanos , Hidrogéis/química
3.
Mol Pharm ; 15(2): 679-694, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29298488

RESUMO

Two major problems in chemotherapy, poor bioavailability of hydrophobic anticancer drug and its adverse side effects causing nausea, are taken into account by developing a sustained drug release vehicle along with enhanced bioavailability using two-dimensional layered double hydroxides (LDHs) with appropriate surface charge and its subsequent embedment in polymer matrix. A model hydrophobic anticancer drug, raloxifene hydrochloride (RH), is intercalated into a series of zinc iron LDHs with varying anion charge densities using an ion exchange technique. To achieve significant sustained delivery, drug-intercalated LDH is embedded in poly(ε-caprolactone) (PCL) matrix to develop intravenous administration and to improve the therapeutic index of the drug. The cause of sustained release is visualized from the strong interaction between LDH and drug, as measured through spectroscopic techniques, like X-ray photoelectron spectroscopy, infrared, UV-visible spectroscopy, and thermal measurement (depression of melting temperature and considerable reduction in heat of fusion), using differential scanning calorimeter, followed by delayed diffusion of drug from polymer matrix. Interestingly, polymer nanohybrid exhibits long-term and excellent in vitro antitumor efficacy as opposed to pure drug or drug-intercalated LDH or only drug embedded PCL (conventional drug delivery vehicle) as evident from cell viability and cell adhesion experiments prompting a model depicting greater killing efficiency (cellular uptake) of the delivery vehicle (polymer nanohybrid) controlled by its better cell adhesion as noticed through cellular uptake after tagging of fluorescence rhodamine B separately to drug and LDH. In vivo studies also confirm the sustained release of drug in the bloodstream of albino rats using polymer nanohybrid (novel drug delivery vehicle) along with a healthy liver vis-à-vis burst release using pure drug/drug-intercalated LDHs with considerable damaged liver.


Assuntos
Antineoplásicos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Neoplasias/tratamento farmacológico , Veículos Farmacêuticos/química , Células 3T3 , Animais , Antineoplásicos/química , Disponibilidade Biológica , Engenharia Química , Preparações de Ação Retardada/química , Difusão , Sistemas de Liberação de Medicamentos , Feminino , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Hidróxidos/química , Concentração Inibidora 50 , Fígado/efeitos dos fármacos , Camundongos , Nanopartículas/química , Polímeros/química , Cloridrato de Raloxifeno/administração & dosagem , Ratos , Difração de Raios X , Compostos de Zinco/química
4.
Nanomedicine ; 14(7): 2131-2141, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30031095

RESUMO

Electrospun scaffold has been developed using biodegradable polymer and age old herbal drug for efficient wound healing patch with much better patient compliance. Positively charged smaller particle size (40 nm) of the drug has been prepared for greater penetration through epidermal barrier to enhance the wound healing activity of drug. Controlled drug release has been understood in terms of interactions between the components through spectroscopic techniques and calorimetric studies. In-vivo study using albino rats shows better wound healing efficiency of scaffold in terms of higher wound area contraction, minimum inflammation, faster epithelialization and vascularization. Cellular studies also endorse the scaffold as better biomaterial. Clinical studies also demonstrate fast healing of different type of wounds in presence of all three wound dressing materials with histological evidences. The complete biodegradation of the patch confirms its green nature of the developed patch.


Assuntos
Materiais Biocompatíveis/química , Medicamentos de Ervas Chinesas/administração & dosagem , Cooperação do Paciente , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Adolescente , Adulto , Idoso , Animais , Preparações de Ação Retardada , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Pessoa de Meia-Idade , Ratos , Adulto Jovem
5.
Bioconjug Chem ; 28(4): 1236-1250, 2017 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-28345891

RESUMO

Biodegradable poly(lactic acid) (PLA) is widely used to fabricate 3D scaffolds for tissue regeneration. However, PLA lacks cell adhering functional moieties, which limit its successful application in tissue engineering. Herein, we have tailored the cell adhesive properties of star shaped poly(d,l-lactide) (ss-PDLLA) by grafting gelatin to their 4 arms. Grafting of gelatin on PDLLA backbone was confirmed by 1H NMR and FTIR. The synthesized star shaped poly(d,l-lactide)-b-gelatin (ss-pLG) exhibited enhanced wettability and protein adsorption. The modification also facilitated better cell adhesion and proliferation on their respective polymer coated 2D substrates, compared to their respective unmodified ss-PDLLA. Further, 3D scaffolds were fabricated from gelatin grafted and unmodified polymers. The fabricated scaffolds were shown to be cytocompatible to 3T3-L1 cells and hemocompatible to red blood cells (RBCs). Cell proliferation was increased up to 2.5-fold in ss-pLG scaffolds compared to ss-PDLLA scaffolds. Furthermore, a significant increase in cell number reveals a high degree of infiltration of cells into the scaffolds, forming a viable and healthy 3D interconnected cell community. In addition to that, burst release of docetaxal (DTX) was observed from ss-pLG scaffolds. Hence, this new system of grafting polymers followed by fabricating 3D scaffolds could be utilized as a successful approach in a variety of applications where cell-containing depots are used.


Assuntos
Adesão Celular , Poliésteres/química , Alicerces Teciduais/química , Células 3T3-L1 , Animais , Materiais Biocompatíveis/química , Proliferação de Células , Docetaxel , Eritrócitos/citologia , Gelatina , Camundongos , Taxoides/metabolismo , Engenharia Tecidual/métodos
6.
Bioconjug Chem ; 28(9): 2254-2265, 2017 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-28753275

RESUMO

Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all of the mentioned shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have shown hypsochromic shifts, suggesting strong interactions between the filler material and the polymer matrix. AG-based nanohybrids have shown greater osteointegration and lower cytotoxicity compared to other nanohybrids as well as pristine bone cement. They have also reduced oxidative stress on cells, resulting in calcification within 20 days of the implantation of nanohybrids into the rabbits. They have significantly reduced the exothermic curing temperature to body temperature and increased the setting time to facilitate practitioners, suggesting that reaction temperature and settling time can be dynamically controlled by varying the concentration of the filler. Thermal stability and enhanced mechanical properties have been achieved in nanohybrids vis-à-vis pure bone cement. Thus, this newly developed nanocomposite can create natural bonding with bone tissues for improved bioactivity, longer sustainability, and better strength in the prosthesis.


Assuntos
Cimentos Ósseos/química , Grafite/química , Nanocompostos/química , Polimetil Metacrilato/química , Aminação , Animais , Substitutos Ósseos/química , Linhagem Celular , Humanos , Teste de Materiais , Nanocompostos/ultraestrutura , Osseointegração , Osteogênese , Polimerização , Coelhos , Temperatura
7.
ACS Appl Mater Interfaces ; 16(14): 17193-17207, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38532651

RESUMO

Functionalized ultraviolet photocurable bisphenol A-glycerolate dimethacrylates with tailorable size have been synthesized as the core, which have further been grafted using the diisocyanate chain end of polyurethane (PU) as the shell to create a core-shell structure of tunable size for a controlled drug delivery vehicle. The core-shell structure has been elucidated through spectroscopic techniques like 1H NMR, FTIR, and UV-vis and their relative shape and size through TEM and AFM morphology. The greater cross-link density of the core is reflected in the higher glass transition temperature, and the improved thermal stability of the graft copolymer is proven from its thermogravimetric analyses. The flow behavior and enhanced strength of the graft copolymers have been revealed from rheological measurements. The graft copolymer exhibits sustained release of the drug, as compared to pure polyurethane and photopolymer, arising from its core-shell structure and strong interaction between the copolymer and drug, as observed through a significant shifting of absorption peaks in FTIR and UV-vis measurements. Biocompatibility has been tested for the real application of the novel graft copolymer in medical fields, as revealed from MTT assay, cell imaging, and cell adhesion studies. The efficacy of controlled release from a graft copolymer has been verified from the gradual cell killing and ∼70% killing in 3 days vs meager cell killing of ∼25% very quickly in 1 day, followed by the increased cell viability of the system treated with the pure drug. The mechanism of slow and controlled drug release from the core-shell structure has been explored. The fluorescence images support the higher cell-killing efficiency as opposed to a pure drug or a drug embedded in polyurethane. Cells seeded on 3D scaffolds have been developed by embedding a graft copolymer, and fluorescence imaging confirms the successful growth of cells within the scaffold, realizing the potential of the core-shell graft copolymer in the biomedical arena.


Assuntos
Portadores de Fármacos , Poliuretanos , Poliuretanos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Polímeros/química
8.
J Mater Chem B ; 12(25): 6221-6241, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38835196

RESUMO

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G', 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.


Assuntos
Hidrogéis , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/síntese química , Humanos , Animais , Ratos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Neurogênese/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células PC12 , Neovascularização Fisiológica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química
9.
ACS Appl Bio Mater ; 6(4): 1536-1545, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-36848659

RESUMO

A flexible and easily processable polymer composite is developed from naturally occurring piezoelectric materials for efficient energy-harvesting applications. Tomato peel (TP)- and cotton (CTN)-based poly(vinylidene fluoride) (PVDF) composites have been prepared and the role of induced electroactive phases have been explored through structural, thermal, and morphological analyses for their applications in energy production. The mechanism of induced piezoelectricity is vividly demonstrated using electromechanical responses and characteristic changes due to induction phenomena. The CTN-based composite generates a maximum output voltage and current of 65 V and 2.1 µA, respectively, as compared to the maximum output voltage and current of 23 V and 0.7 µA in TP-based composites due to the significant induction of the piezoelectric phase in the presence of suitable electroactive cotton. The fabricated device is able to store charges in capacitors and converts the external stress through different motions of the human body to generate a considerable output, which describes the applicability of the material and justifies the potential as an efficient and sustainable biomechanical energy harvester.


Assuntos
Polímeros de Fluorcarboneto , Polímeros , Humanos , Polivinil
10.
ACS Appl Bio Mater ; 6(4): 1566-1576, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-36947679

RESUMO

Direct ink writing (DIW) additive manufacturing is a versatile 3D printing technique for a broad range of materials. DIW can print a variety of materials provided that the ink is well-engineered with appropriate rheological properties. DIW could be an ideal technique in tissue engineering to repair and regenerate deformed or missing organs or tissues, for example, bone and tooth fracture that is a common problem that needs surgeon attention. A critical criterion in tissue engineering is that inserts must be compatible with their surrounding environment. Chemically produced calcium-rich materials are dominant in this application, especially for bone-related applications. These materials may be toxic leading to a rejection by the body that may need secondary surgery to repair. On the other hand, there is an abundance of biowaste building blocks that can be used for grafting with little adverse effect on the body. In this work, we report a bioderived ink made entirely of calcium derived from waste animal bones using a benign process. Calcium nanoparticles are extracted from the bones and the ink prepared by mixing with different biocompatible binders. The ink is used to print scaffolds with controlled porosity that allows better growth of cells. DIW printed parts show better mechanical properties and biocompatibility that are important for the grafting application. Degradation tests and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay study were done to examine the biocompatibility of the extracted materials. In addition, discrete element modeling and computational fluid dynamics numerical methods are used in Rocky and Ansys software programs. This work shows that biowaste materials if well-engineered can be a never-ending source of raw materials for advanced application in orthopedic grafting.


Assuntos
Materiais Biocompatíveis , Cálcio , Animais , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Impressão Tridimensional , Porosidade
11.
ACS Appl Bio Mater ; 6(12): 5644-5661, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37993284

RESUMO

In this work, the glycine-based acryloyl monomer is polymerized to obtain a neurogenic polymeric hydrogel for regenerative applications. The synthesized poly(N-acryloylglycine-acrylamide) [poly(NAG-b-A)] nanohydrogel exhibits high swelling (∼1500%) and is mechanically very stable, biocompatible, and proliferative in nature. The poly(NAG-b-A) nanohydrogel provides a stable 3D extracellular mimetic environment and promotes healthy neurite growth for primary cortical neurons by facilitating cellular adhesion, proliferation, actin filament stabilization, and neuronal differentiation. Furthermore, the protective role of the poly(NAG-b-A) hydrogel for the neurons in oxidative stress conditions is revealed and it is found that it is a clinically relevant material for neuronal regenerative applications, such as for promoting nerve regeneration via GSK3ß inhibition. This hydrogel additionally plays an important role in modulating the biological microenvironment, either as an agonist and antagonist or as an antioxidant. Furthermore, it favors the physiological responses and eases the neurite growth efficiency. Additionally, we found out that the conversion of glycine-based acryloyl monomers into their corresponding polymer modulates the mechanical performance, mimics the cellular microenvironment, and accelerates the self-healing capability due to the responsive behavior towards reactive oxygen species (ROS). Thus, the p(NAG-b-A) hydrogel could be a potential candidate to induce neuronal regeneration since it provides a physical cue and significantly boosts neurite outgrowth and also maintains the microtubule integrity in neuronal cells.


Assuntos
Hidrogéis , Neuritos , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Neuritos/metabolismo , Acrilamida , Estresse Oxidativo , Microambiente Celular , Polímeros/farmacologia , Polímeros/metabolismo , Glicina/farmacologia
12.
Phys Chem Chem Phys ; 14(37): 12844-53, 2012 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-22890196

RESUMO

TiO(2) nanoparticles of different phases play a key role in property alteration of nanocomposite fibers. Polycaprolactone (PCL)/TiO(2) composite fibers were prepared using the electrospinning method. Pure anatase and rutile phases were synthesized using the sol-gel route for nanocomposite synthesis. The Effect of nanoparticle phases on crystallinity of fibers and interaction with polymer molecules have been studied using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, morphology through SEM, surface properties using BET method and wetting property of fibers commencing from contact angle measurement. Biocompatibility and biodegradation of hybrid materials have been studied in simulated body fluid (SBF) and phosphate buffer (PBS), respectively. The anatase phase with smaller particle dimensions exhibited significant improvement of most of the properties as compared to composites made of the rutile phase. Better interaction between polymer chain and anatase particle PCL-A nanocomposite fibers leads to better mechanical property and biocompatibility vis-à-vis PCL-R and pristine PCL fibers. Biocompatibility of PCL nanocomposite has been testified through proliferation of fibroblast cell and its adhesion; MTT (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay demonstrates good proliferation rate for cells on PCL-A nanocomposite fibres.


Assuntos
Nanopartículas Metálicas/química , Poliésteres/química , Titânio/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Nanofibras/química , Nanofibras/toxicidade
13.
J Mater Chem B ; 10(41): 8462-8477, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36197075

RESUMO

A new acrylamide monomer, N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide (M3i), consisting of both isopropyl and isopropylamidopropyl moieties, has been synthesized from isopropylamine and N-isopropylacrylamide via an aza-Michael addition reaction followed by amidation with acryloyl chloride. The homopolymer of M3i (polyM3i) and a series of random copolymers of M3i and poly(ethylene glycol)methyl ether acrylate (PEGA: CH2CHCO2(CH2CH2O)nMe, Mn = 480, n = 9 on average) with varying compositions have been synthesized via reversible addition-fragmentation chain transfer polymerization using 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) as well as 1-phenylethyl phenyl dithioacetate (PEPD) as a RAFT agent. These polymers have been characterized by 1H NMR, FTIR, GPC, UV-Vis, fluorescence, TGDTA, DSC, DLS, and TEM techniques. A lower critical solution temperature (LCST) and glass transition temperature (Tg) for polyM3i prepared using DDMAT were observed at 17 and 133 °C, respectively, while for a polymer formed using PEPD, no LCST was observed until 0 °C and its observed Tg was found at 127.3 °C. The polymers are thermally stable up to 300 °C. Upon an increase in the M3i content in the copolymers, LCST decreases, Tg increases, and the apparent hydrodynamic diameter decreases. Moreover, the effects of concentration and the addition of urea and sodium chloride on the LCST of the copolymer with an LCST close to body temperature were studied. Owing to the incorporation of PEGA, a higher critical micellar concentration and larger TEM particle size of this copolymer were observed with respect to those of polyM3i. The usefulness of the micelles of the copolymers as nano-carriers for the drug doxorubicin was explored. The in vitro tumoricidal activity of the micelles of the doxorubicin-loaded copolymers was also assessed against Dalton's lymphoma cells.


Assuntos
Antineoplásicos , Éteres Metílicos , Micelas , Acrilamida , Cloreto de Sódio , Polímeros/química , Acrilamidas/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Polietilenoglicóis/química , Ureia
14.
Signal Transduct Target Ther ; 6(1): 63, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589586

RESUMO

Novel biocompatible and brush copolymers have been developed for cancer treatment using its controlled drug-release potential. Polyurethane graft on linear dextrin has been synthesized to control the hydrophilic-hydrophobic balance for regulated drug delivery. The properties of the graft copolymers have been tuned through graft density. The prepared grafts are thermally stable and mechanically strong. An injectable hydrogel has been developed by embedding the drug-loaded brush copolymers in methyl cellulose to better control the release for a prolonged period, importantly by keeping the drug release at a constant rate. Cellular studies indicate the biocompatible nature of the brush copolymers whose controlled and slow release of drug exhibit significant cytotoxic effects on cancer cells. Endocytosis of drug tagged contrast agent indicates greater transport of biologically active material inside cell as observed through cellular uptake studies. In vivo studies on melanoma mice exhibit the real efficacy of the controlled drug release from the injectable hydrogel with significant melanoma suppression without any side effects as opposed to severe toxic effects observed in conventional chemotherapy. Special application method of drug-loaded hydrogel just beneath the tumor makes this system incredibly effective through confinement. Thus, brush copolymer injectable hydrogel is a promising vehicle for control release of drug for cancer treatment in future.


Assuntos
Biopolímeros/farmacologia , Hidrogéis/farmacologia , Melanoma Experimental/tratamento farmacológico , Melanoma/tratamento farmacológico , Biopolímeros/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Meios de Contraste/farmacologia , Dextrinas/química , Sistemas de Liberação de Medicamentos , Endocitose/efeitos dos fármacos , Células HeLa , Humanos , Hidrogéis/química , Melanoma/patologia , Melanoma Experimental/genética , Poliuretanos/química
15.
J Phys Chem B ; 125(35): 10009-10017, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34436883

RESUMO

Cationic polymer-based gene delivery vectors suffer from several limitations such as low DNA-loading capacity, poor transfection, toxicity, environmental degradations, etc. Again, very limited works are available addressing the binding interactions in detail at the atomic level explaining the loading capacity, protection ability against harsh environments, and controlled release behavior of the DNA-encapsulated vehicles. Here, a poly(l-lactide) (PLA) nanoparticle-based controlled DNA release system is proposed. The developed vehicle possesses a high DNA-loading capacity and can release the loaded DNA in a controlled manner. Spectroscopic, physicochemical, and molecular simulation techniques (AM1 and atomistic molecular dynamics) have been employed to understand the binding interactions between PLA and DNA molecules enabling high DNA loading, protection against external harsh environments, and controlled DNA release behavior. Methyl thiazolyl tetrazolium (MTT) assay experiments confirm the biocompatible nature of the vehicle. Cellular uptake efficiency and endo-lysosomal escape capabilities have been investigated against HeLA cells. This study, therefore, demonstrates the development of a promising nonviral DNA delivery vector and includes a detailed investigation of the atomic-level interaction behavior between PLA and DNA molecules.


Assuntos
Nanopartículas , Poliésteres , DNA , Células HeLa , Humanos , Tamanho da Partícula
16.
J Photochem Photobiol B ; 212: 112043, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33022468

RESUMO

Alkaline phosphatase (ALP) is an enzyme that actively plays a significant role in the various metabolic processes by transferring a phosphate group to the protein, nucleic acid, etc. The elevated level of ALP in blood plasma is the hallmark of inflammation/cancer. The hyperactive mitochondria in cancer cells produce an excess of ATP to fulfill the high energy demand. Thus, we have developed a fluorescent probe Mito-Phos for ALP, which can detect phosphatase expression in mitochondria in live cells. The probe Mito-Phos has shown ~15-fold fluorescence intensity increments at 450 nm in the presence of 500 ng/mL of ALP. It takes about 60 min to consume the whole amount of ALP (500 ng/mL) in physiological buffer saline. It can selectively react with ALP even in the presence of other probable cellular reactive components. It is highly biocompatible and nontoxic to the live cells. It has shown ALP expression in a dose-dependent manner by providing concomitant fluorescence images in the blue-channel region. It has localized exclusively in the mitochondria in live cells. The probe Mito-Phos is highly biocompatible with the ability to assess ALP expression in mitochondria in live cells.


Assuntos
Fosfatase Alcalina/metabolismo , Materiais Biocompatíveis/química , Corantes Fluorescentes/química , Mitocôndrias/enzimologia , Fosfatase Alcalina/química , Sobrevivência Celular , Regulação Enzimológica da Expressão Gênica , Células HeLa , Humanos , Cinética
17.
J Phys Chem B ; 113(34): 11632-41, 2009 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-19653685

RESUMO

Poly(vinylidene fluoride-co-hexafluoropropylene) (HFP) nanocomposites with layered silicate have been synthesized via the melt extrusion route. The intriguing nanostructure, crystalline structure, morphology, and thermal and mechanical properties of the nanocomposites have been studied and compared critically with pristine polymer. HFP forms intercalated or partially exfoliated nanostructure (or both) in the presence of nanoclay, depending on its concentration. The bombardment of high-energy swift, heavy ions (SHI) on HFP and its nanocomposites has been explored in a wide range of fluence. The nanoclay induces the piezoelectric beta-phase in bulk HFP, and the structure remains intact upon SHI irradiation. SHI irradiation degrades pure polymer, but the degradation is suppressed radically in nanocomposites. The heat of fusion of pristine HFP has drastically been reduced upon SHI irradiation, whereas there are relatively minute changes in nanocomposites. The coarsening on the surface and bulk of HFP and its nanocomposite films upon SHI irradiation has been measured quantitatively by using atomic force microscopy. The degradation has been considerably suppressed in nanocomposites through cross-linking of polymer chains, providing a suitable high-energy, radiation-resistant polymeric material. A mechanism for this behavior originating from the swelling test and gel fraction (chemical cross-linking) as a result of SHI irradiation has been illustrated.


Assuntos
Íons/química , Nanoestruturas/química , Polivinil/química , Silicatos/química , Cristalografia por Raios X , Fulerenos/química , Modelos Moleculares , Tamanho da Partícula , Polivinil/síntese química , Propriedades de Superfície
18.
J Colloid Interface Sci ; 556: 147-158, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31445444

RESUMO

In-situ inclusion of different nanoclays during synthesis results in different level of dispersion of nanoclays in the polymer matrix depending upon the surface modification of the nanoclay. Higher intercalation of the polymer chains within the galleries of organically modified nanoclay results better dispersion as compared to pristine nanoclay. The spectroscopic measurement shows that the extent of interaction between the nanoclay and polymer chains is higher in modified nanoclay nanocomposite which decreases the crystallinity considerably as compared to pristine clay nanocomposite. Interestingly, shape memory behavior measured at physiological temperature (37 °C) improves significantly in presence of organically modified nanoclay while it decreases in presence of unmodified nanoclay in same polyurethane matrix. Complete melting of soft segment along with restricted flipping of hard segment with temperature in presence of extensive interaction in nanocomposite with modified nanoclay helps it to achieve better shape memory behavior against flipping induced stacking of hard segment with temperature along with poor interaction decreases its shape memory behavior in nanocomposite with unmodified nanoclay. Temperature dependent nanostructure reveals the cause of variation in shape memory behavior in presence of organically modified nanoclay. Further, the cell culture studies like cell adhesion, cell viability assay and fluorescence imaging, suggest superior biomaterial of the nanocomposite with modified nanoclay as compared to other composite. Better biodegradable nature of the modified nanocomposite makes it suitable candidate for its potential biomedical applications.


Assuntos
Plásticos Biodegradáveis/química , Argila/química , Impressão Molecular , Nanocompostos/química , Adesão Celular , Linhagem Celular , Humanos , Teste de Materiais , Propriedades de Superfície
19.
J Biomed Mater Res A ; 107(2): 434-444, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30565855

RESUMO

The presence of hydroxyl groups in cyclodextrin (CD) makes it highly hydrophilic and simultaneously allows its chemical modification to graft polyurethane to control the drug release for longer period of time by maintaining the hydrophobic-hydrophilic balance through varying extent of grafting. Grafting of polyurethane on CD is confirmed through 1 H NMR and molecular weight measurement while FTIR and UV visible studies further support grafting and emphasize the interaction among polymer chains as a whole. Degree of grafting is evaluated from the integrated peak area in NMR spectra. Thermal and mechanical measurements show improved stability and strength of the graft polymers with respect to pure CD. The conversion of particle nature of CD to strip-like morphology in graft copolymers is evident from atomic force microscopy. Sustained drug release has been achieved using graft copolymer against burst release from pure CD and specific interactions, as observed through spectroscopy and thermal measurements, are responsible for sustained release of drug. Biocompatibility of graft copolymers has been checked using cellular studies through MTT assay and cell adhesion. Importantly, the cell killing efficiency has been demonstrated by embedding anticancer drug in polymer matrices causing mortality rate of 75% using graft copolymer against scanty 25% using pure drug or drug embedded in CD and the result is understood from the sustained release of drug from the graft copolymer vis-à-vis burst release in other systems. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 434-444, 2019.


Assuntos
Antineoplásicos/administração & dosagem , Ciclodextrinas/química , Preparações de Ação Retardada/química , Dexametasona/administração & dosagem , Poliuretanos/química , Antineoplásicos/farmacologia , Materiais Biocompatíveis/química , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Neoplasias/tratamento farmacológico
20.
J Colloid Interface Sci ; 534: 215-227, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30227378

RESUMO

Hydrophilicity of cyclodextrin is controlled through grafting of polyurethane of varying graft density, thereby maintain the hydrophilic-hydrophobic balance, to sustain the drug delivery rate for better tumor treatment. Grafting is verified through nuclear magnetic resonance (1H NMR) and other spectroscopic techniques along with the hydrodynamic volume measurement of grafted species and the degree of substitution has been calculated from the integrated peak areas. Thermal and mechanical stability of the graft copolymers have improved significantly with respect to cyclodextrin and the formation of smaller blobs having larger in number has been obtained from small angle neutron scattering, atomic force microscopy and optical images. Sustained drug delivery has been achieved using graft copolymer as opposed to burst release in pure cyclodextrin and polyurethane and the phenomenon is understood from the specific interactions, as observed though spectroscopic and thermal measurement, between graft copolymer and drug followed by this novel architecture of the graft copolymers. Biocompatibility of graft copolymers has been checked using cellular studies through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell adhesion. Importantly, the cell killing efficiency has been demonstrated by embedding anti-cancer drug in polymer matrices causing mortality rate of 80% using graft copolymer against meagre 20% using pure drug or drug embedded in cyclodextrin and the result is realised from the sustained release of drug from the graft copolymer vis-à-vis burst release in other systems. Cellular studies have been translated into an animal model showing the efficacy of newly developed patch, made of drug embedded in copolymer, towards the significant suppression of tumors in mice as compared to control. Histopathological images and biochemical parameters indicate the normal body organ/blood in copolymer treated mice against severely damaged organ especially liver/blood in the mice treated with pure drug or drug embedded in cyclodextrin arising from burst release. Thus, graft copolymer with unique architecture is found to be an effective drug delivery vehicle for melanoma cancer treatment without side effect.


Assuntos
Antineoplásicos/química , Ciclodextrinas , Portadores de Fármacos/química , Melanoma/tratamento farmacológico , Poliuretanos , Animais , Antineoplásicos/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos
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