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1.
Int J Biol Macromol ; 277(Pt 1): 134064, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39048012

ABSTRACT

The clinical utility of small-diameter vascular grafts (SDVGs) is limited due to the possibility of thrombosis and intimal hyperplasia. These features can delay the development of a functional endothelial cell (EC) monolayer on the luminal surface of grafts. Therefore, the development and fabrication of vascular grafts (VGs) with comparable extracellular matrix (ECM) functions are mandatory to elicit hemocompatible confluent EC monolayers, and angiogenesis behavior inside the body. To promote the interactions between ECs and the surface of electrospun polyacrylic acid-grafted polyhedral oligomeric silsesquioxane-poly(carbonate-urea)-urethane (PAAc-POSS-PCUU), in this research, the surface of nanofibers was modified by covalently immobilizing extracted soluble proteins from aorta (ESPA) using EDC/NHS chemistry. The ATR-FTIR spectroscopy, WCA, and SEM microscopy confirmed the binding of acrylic acid and soluble vascular proteins on the surface of electrospun fibers. The PAAc-POSS-PCUU nanofibers and engineered biomimetic Pro-PAAc-POSS-PCUU nanofibers exhibited excellent biocompatibility indicated by increased survival rate (p < 0.05). Western blotting revealed the increase of VE-cadherin, Tie-2, vWF, and VEGFR-2 in HUVECs after being plated on PAAc-POSS-PCUU and Pro-PAAc-POSS-PCUU scaffolds, indicating appropriate angiogenesis behavior (p < 0.05). Besides, the antioxidant capacity was induced by the increase of SOD and GPx activity (p < 0.05). Additionally, blood compatibility tests revealed that Pro-PAAc-POSS-PCUU nanofibers accelerate the formation of a single EC layer without hemolysis and platelet adhesion. Taken together, Pro-PAAc-POSS-PCUU nanofibers exhibited excellent blood compatibility, and angiogenesis behavior, making them a promising candidate for clinical applications.


Subject(s)
Biocompatible Materials , Blood Vessel Prosthesis , Neovascularization, Physiologic , Organosilicon Compounds , Polyurethanes , Humans , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Neovascularization, Physiologic/drug effects , Polyurethanes/chemistry , Polyurethanes/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Nanofibers/chemistry , Materials Testing , Animals , Tissue Engineering/methods , Platelet Adhesiveness/drug effects , Angiogenesis
2.
Nanoscale Adv ; 6(3): 990-1000, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38298594

ABSTRACT

Spinal cord injury (SCI) is an incurable and catastrophic health issue with no clinical solution. As part of cascade reactions, the inflammatory process and fibrous glial scar production aggravate the amount of lesion through a secondary damage mechanism, encouraging scientists from other disciplines to investigate new paths for solving this problem. Graphene oxide (GO) and its derivatives are among the most promising biomedical and nerve tissue regeneration materials due to their remarkable chemical, mechanical, and electrical properties. This paper designs and introduces a new GO-based nanomaterial to minimize inflammation and stimulate neurite regrowth. To improve biocompatibility, biodegradability, and cell proliferation, GO plates were modified with polyethylene glycol (PEG) and Au nanoparticles as neuroprotective and antibacterial agents, respectively. Preliminary biological investigations on bone marrow derived mesenchymal stem cells (BM-MSCs) with various concentrations of a graphenic nanocarrier indicated a lack of cell toxicity and an enhancement in BM-MSC proliferation of about 10% after 48 hours. Therapeutic nanostructures were used in the T10 segment of a mouse SCI model. The pathological and immunohistochemical data revealed that refilling tissue cavities, decreasing degeneration, and establishing neuroregeneration resulted in a considerable improvement of hind limb motor function. Furthermore, compared to the nanocomposite mixture alone, the intraspinal delivery of cerebrolysin (CRL) had a more satisfying impact on nerve regrowth, cystic cavity, hemorrhage avoidance, and motor function enhancement. This study demonstrates the potential of graphenic nanomaterials for SCI treatment and neuroregeneration applications.

3.
J Mech Behav Biomed Mater ; 142: 105790, 2023 06.
Article in English | MEDLINE | ID: mdl-37104899

ABSTRACT

Polyphenol extracts derived from plants are expected to have enhanced osteoblast proliferation and differentiation ability, which has gained much attention in tissue engineering applications. Herein, for the first time, we investigate the effects of Prunus amygdalus amara (bitter almond) (BA) extract loaded on poly (ε-caprolactone) (PCL)/gelatin (Gt) nanofibrous scaffolds on the osteoblast differentiation of human dental pulp stem cells (DPSCs). In this regard, BA (0, 5, 10, and 15% wt)-loaded PCL/Gt nanofibrous scaffolds were prepared by electrospinning with fiber diameters in the range of around 237-276 nm. Morphology, composition, porosity, hydrophilicity, and mechanical properties of the scaffolds were examined by FESEM, ATR-FTIR spectroscopy, BET, contact angle, and tensile tests, respectively. It was found that the addition of BA improved the tensile strength (up to 6.1 times), Young's modulus (up to 3 times), and strain at break (up to 3.2 times) compared to the neat PCL/Gt nanofibers. Evaluations of cell attachment, spreading, and proliferation were done by FESEM observation and MTT assay. Cytocompatibility studies support the biocompatible nature of BA loaded PCL/Gt scaffolds and free BA by demonstrating cell viability of more than 100% in all groups. The results of alkaline phosphatase activity and Alizarin Red assay revealed that osteogenic activity levels of BA loaded PCL/Gt scaffolds and free BA were significantly increased compared to the control group (p < 0.05, p < 0.01, p < 0.001). QRT-PCR results demonstrated that BA loaded PCL/Gt scaffolds and free BA led to a significant increase in osteoblast differentiation of DPSCs through the upregulation of osteogenic related genes compared to the control group (p < 0.05). Based on results, incorporation of BA extract in PCL/Gt scaffolds exhibited synergistic effects on the adhesion, proliferation, and osteogenesis differentiation of hDPSCs and was therefore assumed to be a favorable scaffold for bone tissue engineering applications.


Subject(s)
Nanofibers , Prunus dulcis , Humans , Osteogenesis/physiology , Tissue Scaffolds/chemistry , Nanofibers/chemistry , Dental Pulp , Polyesters/chemistry , Tissue Engineering/methods , Cell Differentiation , Stem Cells , Cell Proliferation
4.
Curr Org Synth ; 20(7): 788-811, 2023.
Article in English | MEDLINE | ID: mdl-36654465

ABSTRACT

INTRODUCTION: Nowadays, the catalysts' usage in chemical reactions is unavoidable, and this has led scientists to look for producing and using catalysts which not only cause pollution and toxicity in the reactions and products, but also generate economical benefits. AIMS: Our goal in this paper is to produce a fully biocompatible, non-toxic and inexpensive carbocatalyst with a graphene oxide structure for use in multi-component reactions as a heterogeneous catalyst. METHODS: The research has been carried out to simplify the method of preparing carbocatalysts. In this article, we heated citric acid and thiourea in the simple bottom-up method in which nitrogen and sulfur were atomically inserted into a carbon-carbon bond of graphene oxide. RESULTS: The results have been obtained by comparing graphene oxide quantum dots (GOQDs) and functional graphene oxide quantum dots (GOQDs) and functional nitrogen and sulfur-doped graphene oxide quantum dots (NS-doped-GOQDS) using the produced carbocatalyst in the synthesis of spiro indoline pyrano pyrazoles and highly substituted pyridine derivatives with chemical and pharmacological properties. CONCLUSION: A simple and affordable bottom-up method has been developed to synthesize fluorescent NS-doped-GOQDS by the condensation of CA in the presence of thiourea with water elimination at 185 ℃. After the production of NS-doped-GOQDS, the carbocatalyst is used in the synthesis of spiro[indoline-3,4'-pyrano [2, 3-c]pyrazole] derivatives in four-component reactions and pyridine derivatives in five-component reactions.

5.
J Biomater Sci Polym Ed ; 33(11): 1415-1434, 2022 08.
Article in English | MEDLINE | ID: mdl-35380915

ABSTRACT

This study developed a platform for fabricating small-diameter vascular grafts using electrospun poly(carbonate-urea)urethane bonded with different concentrations of POSS nanocage. The characteristics of electrospun POSS-PCUUs were investigated by ATR-FTIR, 1HNMR, EDS, SEM, AFM, WCA, and DSC analyses. Besides, mechanical attributes such as tensile strength, modulus, elastic recovery, and inelastic behaviors were monitored. The survival rate and cellular attachment capacity were studied using human endothelial cells during a 7-day culture period. The results showed that electrospun nanofibers with 6 wt.% POSS-PCUU had better surface properties in terms of richness of POSS nanocage with notable improved mechanical strength and hysteresis loss properties (p < 0.05). The surface roughness of electrospun 6 wt.% POSS-PCUU reached 646 ± 10 nm with statistically significant differences compared to the control PCUU and groups containing 2, 4 wt.% POSS-PCUU (p < 0.05). The addition of 6 wt.% POSS increased the ultimate mechanical strength of nanofibers related to control PCUU and other groups (p < 0.05). The expansion of human endothelial cells on the 6 wt.% POSS-PCUU surface increased the viability reaching maximum levels on day 7 (p < 0.05). Immunofluorescence imaging using DAPI staining displayed the formation single-layer endothelial barrier at the luminal surface, indicating an appropriate cell-to-cell interaction.


Subject(s)
Nanocomposites , Urethane , Carbonates , Endothelial Cells , Humans , Nanocomposites/chemistry , Surface Properties , Urea
6.
Adv Pharm Bull ; 11(3): 477-489, 2021 May.
Article in English | MEDLINE | ID: mdl-34513622

ABSTRACT

Purpose: In last decades, by increasing multi-drug resistant microbial pathogens an urgent demand was felt in the development of novel antimicrobial agents. Methods: Promising nanocomposites composed of clay/alginate/imidazolium-based ionic liquid, have been developed via intercalation of calcium alginate and ionic liquid by ion exchange method. These tailored nanocomposites were used as nanocarriers to simultaneously deliver methotrexate (MTX), and ciprofloxacin (CIP), as anticancer and antibacterial agents, respectively to MCF-7 breast cancer cells. Nanocomposites were fully characterized by scanning electron microscopy studies (SEM), X-ray diffraction (XRD), Fourier transforms infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA) methods. The in vitro antimicrobial potential of the mentioned nanocomposites in free and dual-drug loaded form was investigated on Pseudomonas aeruginosa and Escherichia coli bacteria. The antitumor activity of nano-formulations was evaluated by both MTT assay and cell cycle arrest. Results: The dual drug-loaded nanocomposites with exceptionally high loading efficiency (MTX: 99 ±0.4% and CIP: 98 ±1.2%) and mean particle size of 70 nm were obtained with obvious pH-responsive MTX and CIP release (both drugs release rate was increased at pH 5.8 compared to 7.4). The antibacterial activity of CIP-loaded nanocomposites was significantly higher in comparison with free CIP (P <0.001). The antitumor activity results revealed that MTX cytotoxicity on MCF-7 cells was significantly higher in nano-formulations compared to free MTX (P <0.001). Both MTX-loaded nanocomposites caused S-phase arrest in MCF-7 cells compared to non-treated cells (P ˂ 0.001). Conclusion: Newly developed smart nanocomposites are potentially effective pH-sustainable delivery systems for enhanced tumor therapy.

7.
Hum Cell ; 34(6): 1682-1696, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34533763

ABSTRACT

Since polymeric nanofibrous scaffolds have been widely used in tissue regeneration, the risk of bacterial infections should not be neglected. In the present work, poly-caprolactone-silk fibroin-soluble eggshell membrane-silver nanoparticles (PCL-SF-SESM-AgNPs) and caprolactone-silk fibroin-soluble eggshell membrane-chitosan (PCL-SF-SESM-CS) scaffolds were fabricated via the electrospinning method for cutaneous regeneration. The composition, morphology, hydrophilicity, and mechanical features of prepared scaffolds were evaluated using Fourier transform infrared (FT-IR), scanning electron microscope (SEM), tensile, and water contact angle tests. The existence of AgNPs in PCL/SF/SESM/AgNPs nanofibers was confirmed by UV-visible, Transmission electron microscopes (TEM), and X-Ray Diffraction (XRD) patterns. Besides, cell adhesion, proliferation, and differentiation process of cutaneous progenitor cells, namely basal cell carcinoma (BCCs), toward keratinocyte-like cells were evaluated using MTT analysis, DAPI, Immunofluorescence imaging (IF), and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR) assay. The results indicated that prepared nanofibrous mats are appropriate candidates for cutaneous regeneration and in advanced in vivo applications could be used. Lastly, the antimicrobial potential of prepared nanofibers against microorganisms such as E. coli, S. aureus, and C. Albicans was analyzed using the disc diffusion method. Results revealed that chitosan-containing nanofibrous scaffolds indicate inhibition against S. aureus, but PCL-SF-SESM as control group not. In addition, against C. albicans any antifungal activity was not observed.


Subject(s)
Anti-Bacterial Agents , Fibroins , Nanofibers , Regeneration/physiology , Regenerative Medicine/methods , Skin Physiological Phenomena , Tissue Engineering/methods , Tissue Scaffolds , Chitosan/chemistry , Chitosan/pharmacology , Drug Resistance, Bacterial , Escherichia coli/drug effects , Fibroins/chemistry , Fibroins/pharmacology , Humans , Nanofibers/chemistry , Polymers , Silver/chemistry , Silver/pharmacology , Staphylococcus aureus/drug effects , Tissue Scaffolds/chemistry
8.
RSC Adv ; 11(33): 19992-20002, 2021 Jun 03.
Article in English | MEDLINE | ID: mdl-35479903

ABSTRACT

Advanced therapeutic strategies include the incorporation of biomaterials, which has been identified as an effective method in treating unsolved diseases, such as spinal cord injury. During the acute phase, cascade responses involving cystic cavitation, fibrous glial scar formation, and myelin-associated dissuasive accumulation occur in the microenvironment of the spinal cord lesion. Graphene oxide (GO)-based materials, due to their extraordinary chemical, electrical and mechanical properties and easy to modify structure, are considered as rising stars in biomaterial and tissue engineering. In order to enhance the biodegradability and biocompatibility of GO, cell proliferation may be appropriately designed and situated at the lesion site. In this study, chitosan (CS) and polyethylene glycol (PEG) were grafted onto GO sheets. CS is a natural non-toxic polymer with good solubility and high biocompatible potential that has been used as an anti-inflammatory and anti-oxidant agent. Furthermore, PEG, a synthetic neuroprotective polymer, was used to develop the pharmacokinetic activity and reduce the toxicity of GO. Herein we report a novel nanocomposite consisting of PEG and CS with a potential advantage in spinal tissue regeneration. The preliminary in vitro study on mesenchymal stem cells (MSCs) has demonstrated that the prepared nanocomposites are not only non-toxic but also increase (by nearly 10%) cell growth. Finally, the use of mixed nanocomposites in the spinal cord injury (SCI) model resulted in good repair and inflammation decline after two weeks, such that walking and functional recovery scores of the hind limbs of mice were improved by an average of 6 points in the treatment group.

9.
Photodiagnosis Photodyn Ther ; 33: 102144, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33307234

ABSTRACT

Gold nanoparticles (GNPs) indicate potential in the development of cancer treatments as vehicles for thermal damage of cancer cells because of their photothermal heating capability. Herein, we aim to investigate the effect of GNPs geometry as photothermal transducers on cellular uptake and photothermal therapy (PTT) efficacy. For this aim, seven different shapes of anisotropic GNPs: stars, hollow, rods, cages, spheres, Fe-Au, and Si-Au core shells were synthesized and investigate the effect of shape on GNPs optical properties. The physic-chemical characterization of prepared GNPs was investigated by UV-vis, DLS-Zeta, and TEM analysis. The effect of GNPs geometry on cellular uptake was investigated by ICP-MS and flow cytometry method. The PTT potential of these GNPs was compared on MCF7 cells in vitro using MTT assay, cell cycle, and Annexin-V apoptosis assay. While all these GNPs could absorb and convert near-infrared light into heat, gold nanostars exhibited the lowest cytotoxicity, highest cellular uptake and highest heat generation compared to other structures. Following photothermal treatment, due to substantial heat production in MCF7 cells, the apoptosis induction rate was greatly increased for all anisotropic gold nanostructures (stars, hollow, rods, and cages) especially gold nanostars. Combined, we can conclude that GNPs geometry affects cellular uptake and heat generation amount as well as cell destruction by apoptosis pathway. The gold nanostar is promising candidates for photothermal destruction.


Subject(s)
Metal Nanoparticles , Neoplasms , Photochemotherapy , Cell Line, Tumor , Gold , Humans , Neoplasms/drug therapy , Photochemotherapy/methods , Photosensitizing Agents , Phototherapy
10.
J Biol Eng ; 13: 79, 2019.
Article in English | MEDLINE | ID: mdl-31673286

ABSTRACT

BACKGROUND: The main issue in cutaneous regeneration is to develop engineered scaffolds based on natural extracellular matrix to promote dynamics of skin progenitor cells and accelerate differentiation into mature keratinocytes. METHODS: In this study, nanofibrous scaffolds composed of a blend poly (ɛ-caprolactone) (PCL), silk fibroin (SF), soluble eggshell membrane (SESM), and Aloe vera (AV) gel were developed by electrospinning method and human basal cells were used to examine differentiation capacity toward keratinocyte-like cells. For this propose, cells were allocated to four distinct groups; control, PCL/SF, PCL/SF/SESM, and PCL/SF/SESM/AV. In all groups, cells were incubated with differentiation medium. Morphology, composition, hydrophilicity and mechanical features of PCL/SF, PCL/SF/SESM and PCL/SF/SESM/AV nanofibers were studied by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), water contact angle and tensile tests. To examine the orientation of basal cells to mature keratinocytes, we performed immunofluorescence analysis by monitoring cytokeratin-19. The expression of genes such as involucrin, keratin-14 and -5 was monitored by real-time PCR assay. RESULTS: PCL/SF, PCL/SF/SESM, and PCL/SF/SESM/AV had suitable physic chemical indices and biological activities to be applied as biomimetic scaffolds for the restoration cutaneous tissue. Compared to control, we found an increased basal cell proliferation at 7 and 14 days after plating on scaffolds and reach maximum levels in group PCL/SF/SESM/AV on day 14 (p < 0.05). Electron microscopy showed cell flattening, morphological adaptation. An integrated cell-to-cell connection was generated after cell seeding on scaffolds in all groups. Immunofluorescence imaging showed the ability of basal cells to synthesize cytokeratin-19 in PCL/SF, PCL/SF/SESM, and positive control cells after exposure to differentiation medium. However, these values were less in PCL/SF/SESM/AV compared to other groups. Real-time PCR analysis showed the potency of all scaffolds to induce the transcription of involucrin, keratin-14 and -5, especially involucrin in PCL/SF/SESM/AV group compared to the negative control. CONCLUSION: Modulation of scaffolds with natural biopolymers could enable us to synthesize structures appropriate for cutaneous regeneration.

11.
Sci Rep ; 9(1): 14686, 2019 10 11.
Article in English | MEDLINE | ID: mdl-31604983

ABSTRACT

Complexes based on heavy metals have great potential for the treatment of a wide variety of cancers but their use is often limited due to toxic side effects. Here we describe the synthesis of two new cadmium complexes using N(4)-phenyl-2-formylpyridine thiosemicarbazone (L1) and 5-aminotetrazole (L2) as organic ligands and the evaluation of their anti-cancer and nephrotoxic potential in vitro. The complexes were characterized by Single-crystal X-ray data diffraction, 1HNMR, FT-IR, LC/MS spectrometry and CHN elemental analysis. Next, cytotoxicity of these cadmium complexes was evaluated in several cancer cell lines, including MCF-7 (breast), Caco-2 (colorectal) and cisplatin-resistant A549 (lung) cancer cell lines, as well as in conditionally-immortalized renal proximal tubule epithelial cell lines for evaluating nephrotoxicity compared to cisplatin. We found that both compounds were toxic to the cancer cell lines in a cell-cycle dependent manner and induced caspase-mediated apoptosis and caspase-independent cell death. Nephrotoxicity of these compounds was compared to cisplatin, a known nephrotoxic drug, in vitro. Our results demonstrate that compound {2}, but not compound {1}, exerts increased cytotoxicity in MCF-7 and A549 cell lines, combined with reduced nephrotoxic potential compared to cisplatin. Together these data make compound {2} a likely candidate for further development in cancer treatment.


Subject(s)
Antineoplastic Agents/pharmacology , Cadmium/pharmacology , Coordination Complexes/pharmacology , Neoplasms/drug therapy , A549 Cells , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cadmium/chemistry , Cell Cycle/drug effects , Cisplatin/adverse effects , Cisplatin/pharmacology , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Humans , Kidney/drug effects , Kidney/pathology , Ligands , MCF-7 Cells , Neoplasms/pathology , Spectroscopy, Fourier Transform Infrared , Tetrazoles/chemical synthesis , Tetrazoles/chemistry , Tetrazoles/pharmacology , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacology
12.
Int J Biol Macromol ; 135: 829-838, 2019 Aug 15.
Article in English | MEDLINE | ID: mdl-31158422

ABSTRACT

For the first time, nano carboxymethyl cellulose (NCMC) was synthesized via cellulose nanocrystal carboxymethylation. This nanomaterial was magnetized and used in bilayer alginate-chitosan hydrogel beads formulation to develop eco-friendly, smart, and magnetic sensitive hydrogel beads for the controlled pH-sensitive release of dexamethasone as a model drug. Water-soluble nanocrystalline cellulose (NCMC) and bilayer hydrogel beads were characterized in terms of size, surface morphology, surface modification, crystallinity, drug loading content, and in vitro drug release profile using various technics. Furthermore, the swelling behavior of hydrogels was examined and reported in three buffer media. The NCMCs improved drug loading capacity and swelling properties and also regulated drug release behavior of hydrogels. The hydrogel beads swelling specification exhibited a higher index in phosphate buffer at pH 5.8 than at pH 1.2 and 7.4. Besides, in vitro release of beads revealed excellent pH-sensitive drug release profiles and prevented release in the gastrointestinal tract. The beads showed high pH sensitivity for dexamethasone drug in pH 5.8 in compared to other pH media. The obtained results could introduce hydrogel beads as a high potential drug delivery system.


Subject(s)
Alginates/chemistry , Carboxymethylcellulose Sodium/chemistry , Chitosan/chemistry , Drug Carriers/chemistry , Hydrogels/chemistry , Microspheres , Nanostructures/chemistry , Delayed-Action Preparations , Drug Carriers/metabolism , Gastrointestinal Tract/metabolism , Hydrogen-Ion Concentration , Magnets/chemistry , Solubility , Water/chemistry
13.
Anticancer Agents Med Chem ; 17(14): 1898-1914, 2018 Feb 07.
Article in English | MEDLINE | ID: mdl-28530541

ABSTRACT

BACKGROUND: The need for therapeutically effective anticancer drug delivery systems constantly persuades researchers to explore novel strategies. OBJECTIVE: In this study a novel cubane based antibacterial nanocomposite was tailored as dual chemotherapy drug delivery vesicle in order to increase the therapeutic outcome in cancer therapy. METHOD: The physico-chemical characterization of engineered nanocarrier was assessed by Fourier transforms infrared spectroscopy (FTIR), Hydrogen nuclear magnetic resonance spectroscopy (1H NMR), Thermogravimetric analysis (TGA), and Field emission scanning electron microscopy-energy dispersive using X-ray (FESEMEDX). The antibacterial activity of novel developed nanocomposite was tested by determining minimum inhibitory concentration (MIC) values against Pseudomonas aeruginosa, Escherichia Coli and Candida albicans. RESULTS: In order to investigate the efficacy of novel engineered nanocomposite (with average particle size of 50 nm) as dual anticancer drug delivery, DOX and MTX were bind to nanocarrier with encapsulation efficiency and loading content of around 97.3 ± 2.7% and 20.8 ± 1.6 %, respectively. Dual drugs released simultaneously with distinct tumor targeted, pH responsive sustained release manner. Moreover, the probable antitumoral activity of this engineered nanocomposite system against MCF7 cell lines was evaluated by MTT assay and cell cycle studies. The outcomes showed that novel engineered nanocomposite had no cytotoxic effects, while DOX@MTX-loaded nanocomposite possessed higher growth inhibition property and higher S-phase arrest as compared to cells treated with DOX@MTX alone. CONCLUSION: It was concluded that this novel cubane based drug delivery vehicle could process antibacterial and anticancer therapeutics spontaneously, representing promising tumor targeted system in nanomedicine.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Methotrexate/pharmacology , Nanocomposites/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Candida albicans/drug effects , Cell Cycle/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Doxorubicin/chemistry , Drug Screening Assays, Antitumor , Escherichia coli/drug effects , Humans , MCF-7 Cells , Methotrexate/chemistry , Molecular Structure , Pseudomonas aeruginosa/drug effects , Structure-Activity Relationship , Tumor Cells, Cultured
14.
ACS Biomater Sci Eng ; 4(1): 184-192, 2018 Jan 08.
Article in English | MEDLINE | ID: mdl-33418688

ABSTRACT

In this work, photoresponsive nanomechanical systems were prepared through the intercalation of positively charged photoswitching molecular jacks (azobenzene ionic liquids, Azo-ILs) within montmorillonite (MMT) layers (MMT@Azo-ILs). The study shows that MMT@Azo-ILs are photosensitive and the synthesized molecular jacks could change the basal distances of MMT layers upon UV irradiation. These changes come from changes in the structure and geometry of Azo molecules (i.e., cis-trans isomerization) between clay layers upon UV irradiation. The prepared photoresponsive nanomechanical systems were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDX), field-emission scanning electron microscope (FE-SEM). Moreover, the in vitro release studies were performed in different conditions (upon UV irradiation and darkness) in pH 5.8 at 34 ± 1 °C, and it was found that the release rates from drug loaded MMT@Azo-ILs were higher upon UV irradiation in comparison with the release rates in darkness. According to the release studies, the prepared photoresponsive carriers might be considered as an excellent potential candidate in order to formulate smart sunscreens.

15.
Drug Dev Ind Pharm ; 43(12): 1963-1977, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28724328

ABSTRACT

Due to multidrug resistance of cancer tissues and immune-suppression of cancerous patients during chemotherapy in one hand and the use of tetrazole derivatives in medicine because of its anticancer, antifungal, and antiviral properties, on the other, we were encouraged to design novel smart antibacterial nanocomposites-based polymer of tetrazole as dual anticancer drug delivery systems. The structures of nanocomposites characterized by FTIR, 1H NMR, FESEM-EDX, and TGA analyzes and antibacterial activity of smart carriers were evaluated by determination of minimum inhibitory concentration (MIC) values against some bacteria and fungi. Then, the pH-responsive manner of both nanocomposites was proved by checking their release profiles at pH of the physiological environment (pH 7.4) and pH of tumor tissues (mildly acidic). Finally, the potential antitumoral activity of these nanocomposite systems against MCF7 cell lines was evaluated by MTT assay and cell cycle studies. The results demonstrated that the novel developed nanocomposites not only meet our expectations about simultaneous release of two anticancer drugs according to the predicted profile but also showed antibacterial and anticancer properties in vitro experimental. Moreover, it was proved that these carriers have tremendous potential in multifunctional drug delivery in cancer therapy.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Antineoplastic Agents/administration & dosage , Drug Carriers/chemistry , Nanoparticles/chemistry , Tetrazoles/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Delivery Systems , Humans , Hydrogen-Ion Concentration , MCF-7 Cells
16.
Artif Cells Nanomed Biotechnol ; 45(8): 1509-1520, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27899033

ABSTRACT

Here a novel antibacterial nanocomposite was developed for combination cancer therapy. The synthesized nanocarrier was characterized by FTIR, 1H NMR, thermogravimetric analysis (TGA), and FESEM-EDX. Its antibacterial activity was assessed by determining minimum inhibitory concentration (MIC) values. Doxorubicin (DOX) and methotrexate (MTX) conjugation with nanocarrier sustained the release of both drugs with apparent pH-triggered manner. Co-administration of DOX with MTX leads to an efficient anticancer performance to MCF7 cell lines verified by qRT-PCR and MTT assay tests. It was concluded that this novel drug delivery vehicle makes antibacterial and anticancer therapeutic processes proceed spontaneously, representing more efficient drug delivery system in nanomedicine. [Formula: see text].


Subject(s)
Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Nanocomposites/chemistry , Polymers/chemistry , Polymers/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Carriers/pharmacology , Drug Liberation , Humans , MCF-7 Cells , Nanoparticles/chemistry , Silicon Dioxide/chemistry
17.
Eur J Pharm Sci ; 93: 64-73, 2016 Oct 10.
Article in English | MEDLINE | ID: mdl-27497878

ABSTRACT

A smart pH-responsive drug nano-carrier for controlled release of anti-cancer therapeutics was developed through a facile route. The nano-carrier consisted of two main parts: first, the nano-container part (that mesoporous silica nanoparticles (MCM-41) were selected for this aim); and second, pH-sensitive gatekeepers (that a pH-sensitive polymer, Poly4-vinylpyridine, played this role). In the first step, MCM-41 was synthesized via template assisted sol-gel process. In the second step, polymerizable functional groups were attached onto pore entrances rather than inside walls. In the third step, polymeric gatekeepers were introduced onto pore entrances via precipitation polymerization of functionalized MCM-41 with monomers. Different methods and analysis, such as Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Powder Diffraction (XRD), Thermo-Gravimetric Analysis (TGA), Energy-Dispersive X-ray Spectroscopy (EDX), Zeta Potentials, Dynamic Light Scattering (DLS), Field Emission Scanning Electron Microscope (FE-SEM) and Transmission Electron Microscopy (TEM) were employed to approve the successful attachment of gatekeepers. Furthermore, the release studies of methotroxate (MTX), an anti-cancer drug, were performed in different media (pH4, 5.8 and 7.4) at 37±1°C. The release profiles and curves show that the release rates are completely pH-dependent and it proceeds with a decrease in pH. It is concluded that in the higher pH the gatekeepers are in their close state, but they switch to the open state as a consequence of repulsive forces between positively charged polymer chains appear in acidic media. The results suggest that this smart nano-carrier can be considered as an appropriate candidate to deliver therapeutics to cancerous tissues.


Subject(s)
Antineoplastic Agents/administration & dosage , Drug Carriers , Hydrogen-Ion Concentration , Nanoparticles , Polymers/chemistry , Silicon Dioxide/chemistry , In Vitro Techniques , Microscopy, Electron , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
18.
Artif Cells Nanomed Biotechnol ; 44(1): 277-84, 2016.
Article in English | MEDLINE | ID: mdl-25111051

ABSTRACT

Hydroxyapatite (HA), the main mineral component of bones and teeth, was synthesized by using the reaction between calcium nitrate tetrahydrate Ca(NO3)2∙4H2O and diammonium hydrogen phosphate (NH4)2HPO4 (DAHP) with a chemical precipitation method. The objective of this study is to utilize novel inorganic-organic nanocomposites for biomedical applications. HA is an inorganic component (75% w) and chitosan, alginate and albumin (Egg white) are organic components of nanocomposites (25% w). Nanocomposites were prepared in deionized water solutions, at room temperature, using a mechanical and magnetic stirrer for 48 h. The microstructure and morphology of sintered n-HAP were tested at different preheating temperature and laser sintering speed with scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR).


Subject(s)
Biocompatible Materials/chemical synthesis , Dental Materials/chemical synthesis , Durapatite/chemical synthesis , Nanocomposites/chemistry , Albumins/chemistry , Albumins/pharmacology , Alginates/chemistry , Alginates/pharmacology , Biocompatible Materials/pharmacology , Calcium Compounds/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Chemical Precipitation , Chitosan/chemistry , Chitosan/pharmacology , Dental Materials/pharmacology , Durapatite/pharmacology , Fibroblasts/cytology , Fibroblasts/drug effects , Glucuronic Acid/chemistry , Glucuronic Acid/pharmacology , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacology , Humans , Materials Testing , Microscopy, Electron, Scanning , Nanocomposites/ultrastructure , Nitrates/chemistry , Phosphates/chemistry , Spectroscopy, Fourier Transform Infrared
19.
J Drug Target ; 22(4): 327-42, 2014 May.
Article in English | MEDLINE | ID: mdl-24404962

ABSTRACT

In this paper novel stimuli-responsive cationic mesoporous silica nanoparticles (MSNs) were fabricated through the facile polymerization method. The synthesis process was characterized and validated by Fourier transform infrared spectroscopy and hydrogen nuclear magnetic resonance spectroscopy. The prepared nanoparticles were characterized using scanning electron microscopy (SEM), Zeta potential and thermogravimetric analysis methods. SEM results revealed the uniformity in size and shape of nanoparticles with a mean diameter of approximately 60 nm. Two model anticancer drugs, Doxorubicin (DOX) and Methotroxate (MTX) were loaded effectively to functionalized MSNs through electrostatic interactions. Our developed HPLC-UV method was applied for simultaneous determination of DOX and MTX. Modified MSNs yielded a pH and temperature-triggered release of entrapped drugs at tumor tissue environment (lower pH and higher temperature than physiological condition). In-vitro cytotoxicity assay showed that the blank carrier showed no cytotoxicity on both A549 and MCF7 cells at different amounts after incubation for 72 h confirming its suitability as a drug carrier. Multi anticancer drug-loaded MSNs, in the other hand, caused an efficient anticancer performance verified by DAPI staining and MTT assay tests. It was concluded that our findings may open the possibilities for cooperative thermo and pH-responsive targeted delivery of DOX and MTX to the cancerous tissues.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Drug Carriers/chemistry , Nanocomposites/chemistry , Silicon Dioxide/chemistry , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Humans , Magnetic Resonance Spectroscopy , Methotrexate/administration & dosage , Methotrexate/pharmacology , Microscopy, Electron, Scanning , Particle Size , Spectroscopy, Fourier Transform Infrared , Surface Properties , Thermogravimetry
20.
Des Monomers Polym ; 15(4): 379-388, 2012.
Article in English | MEDLINE | ID: mdl-38812894

ABSTRACT

Polymeric forms of ionic liquids have many potential applications because of their ionic nature. Two ionic liquid monomers, 1-(4-vinylbenzyl)-3-methyl imidazolium hexafluorophosphate (VMIH) and 1-(4-vinylbenzyl)-4-(dimethylamino)-pyridinium hexafluorophosphate (VDPH), were synthesized through the quaternization of N-methylimidazole and 4-(dimethylamino) pyridine with 4-vinylbenzylchloride, respectively, and a subsequent anion exchange reaction with potassium hexafluorophosphate. The homopolymers of VMIH, VDPH, and its copolymers with methyl styrene (in various mole ratios) were synthesized by free radical polymerizations at 70 °C using α,α'-azobis(isobutyronitrile) as an initiator. Anionic drug molecule, naproxen (an anti-inflammatory drug), was effectively loaded into these positive charges polymers (PCP) and remained inside of the PCP under acidic environment (pH 2-6.5). The amount of loading of drug was increased with increasing positive charge densities resulting from the increasing number of ionic liquids groups. PCP as a controllable release of anionic drug molecules can be used as an oral delivery drug systems targeting at intestine. This drug can be remained trapped in the polymers when passing through the acidic and neutral environment and be released in intestine, where the environmental pH is close to basic.

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