scholarly journals Differentiating Co-Delivery of Bisphosphonate and Simvastatin by Self-Healing Hyaluronan Hydrogel Formed by Orthogonal “Clicks”: An In-Vitro Assessment

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2106
Author(s):  
Dmitri A. Ossipov ◽  
Mads Lüchow ◽  
Michael Malkoch
Keyword(s):  
Targeted Delivery ◽  
Release Kinetics ◽  
Bone Diseases ◽  
Bone Tissue Regeneration ◽  
Potential Candidate ◽  
Self Healing ◽  
Network Properties ◽  
Multiple Drugs ◽  
Hydrophobic Ligands

Due to its unique properties resembling living tissues, hydrogels are attractive carriers for the localized and targeted delivery of various drugs. Drug release kinetics from hydrogels are commonly controlled by network properties and the drug-network interactions. However, and simultaneously, the programmable delivery of multiple drugs with opposing properties (hydrophilicity, molecular weight, etc.) from hydrogels with determined network properties is still challenging. Herein, we describe the preparation of injectable self-healing hyaluronic acid (HA) hydrogels that release hydrophobic simvastatin and hydrophilic aminobisphosphonate (BP) drugs independently in response to acidic and thiol-containing microenvironments, respectively. We apply a prodrug strategy to BP by conjugating it to HA via a self-immolative disulfide linker that is stable in the blood plasma and is cleavable in the cytoplasm. Moreover, we utilize HA-linked BP ligands to reversibly bind Ca2+ ions and form coordination hydrogels. Hydrazone coupling of hydrophobic ligands to HA permits the encapsulation of simvastatin molecules in the resulting amphiphilic HA derivative and the subsequent acid-triggered release of the drug. The conjugation of BP and hydrophobic ligands to HA enables preparation of both bulk self-healing hydrogels and nanogels. Moreover, the developed hydrogel system is shown to be multi-responsive by applying orthogonally cleavable linkers. The presented hydrogel is a potential candidate for the combination treatment of osteoporosis and bone cancers as well as for bone tissue regeneration since it can deliver bone anabolic and anti-catabolic agents in response to bone diseases microenvironments.

scholarly journals Formulation Development and Evaluation of Drug Release Kinetics from Colon-Targeted Ibuprofen Tablets Based on Eudragit RL 100-Chitosan Interpolyelectrolyte Complexes

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kenneth Chibuzor Ofokansi ◽  
Franklin Chimaobi Kenechukwu
Keyword(s):  
Drug Release ◽  
Targeted Delivery ◽  
Release Kinetics ◽  
Local Treatment ◽  
Wet Granulation ◽  
Formulation Development ◽  
Swelling Properties ◽  
Interpolyelectrolyte Complexes ◽  
Bowel Diseases

Colon-targeted drug delivery systems (CTDDSs) could be useful for local treatment of inflammatory bowel diseases (IBDs). In this study, various interpolyelectrolyte complexes (IPECs), formed between Eudragit RL100 (EL) and chitosan (CS), by nonstoichiometric method, and tablets based on the IPECs, prepared by wet granulation, were evaluated as potential oral CTDDSs for ibuprofen (IBF). Results obtained showed that the tablets conformed to compendial requirements for acceptance and that CS and EL formed IPECs that showed pH-dependent swelling properties and prolonged the in vitro release of IBF from the tablets in the following descending order: 3 : 2 > 2 : 3 > 1 : 1 ratios of CS and EL. An electrostatic interaction between the carbonyl (–CO–) group of EL and amino (–) group of CS of the tablets formulated with the IPECs was capable of preventing drug release in the stomach and small intestine and helped in delivering the drug to the colon. Kinetic analysis of drug release profiles showed that the systems predominantly released IBF in a zero-order manner. IPECs based on CS and EL could be exploited successfully for colon-targeted delivery of IBF in the treatment of IBDs.

scholarly journals Conducting PEEK Nanocomposites with Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multi-Modal Therapeutic Applications

2020 ◽  
Author(s):  
Miaomiao He ◽  
Ce zhu ◽  
Huan Xu ◽  
dan Sun ◽  
Chen Chen ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Repair ◽  
Graphene Nanosheets ◽  
Biomechanical Properties ◽  
Bone Diseases ◽  
Bone Tissue Regeneration ◽  
Order Of Magnitude

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades due to its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue towards its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Due to the formation of electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved twelve order of magnitude enhancement in its electrical conductivity, and have enabled electrophoretic deposition of bioactive/anti-bacterial coating consisting of stearyltrimethylammonium chloride (STAC) modified hydroxyapatite (HA). The coated composite implant showed significant boosting of BMSC cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers have enabled laser induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 oC in 150 s. The unique multi-functionality of our composite implant has also been demonstrated for photothermal applications such as enhancing bacterial (E. coli and S. aureus) eradication and tumor cell (MG63) inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multi-functional implant in bone repair applications as well as multi-modal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis

scholarly journals Bone Diseases: Current Approach and Future Perspectives in Drug Delivery Systems for Bone Targeted Therapeutics

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 875 ◽  
Author(s):  
Giulia Chindamo ◽  
Simona Sapino ◽  
Elena Peira ◽  
Daniela Chirio ◽  
Mónica Cristina Gonzalez ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Targeted Delivery ◽  
Release Kinetics ◽  
Bone Cancer ◽  
Molecular Complexes ◽  
Delivery Systems ◽  
Current Approach ◽  
Bone Diseases ◽  
Mobility Limitations ◽  
Potential Strategy

Bone diseases include a wide group of skeletal-related disorders that cause mobility limitations and mortality. In some cases, e.g., in osteosarcoma (OS) and metastatic bone cancer, current treatments are not fully effective, mainly due to low patient compliance and to adverse side effects. To overcome these drawbacks, nanotechnology is currently under study as a potential strategy allowing specific drug release kinetics and enhancing bone regeneration. Polymers, ceramics, semiconductors, metals, and self-assembled molecular complexes are some of the most used nanoscale materials, although in most cases their surface properties need to be tuned by chemical or physical reactions. Among all, scaffolds, nanoparticles (NPs), cements, and hydrogels exhibit more advantages than drawbacks when compared to other nanosystems and are therefore the object of several studies. The aim of this review is to provide information about the current therapies of different bone diseases focusing the attention on new discoveries in the field of targeted delivery systems. The authors hope that this paper could help to pursue further directions about bone targeted nanosystems and their application for bone diseases and bone regeneration.

scholarly journals Inhibitory Effects of N-[2-(4-acetyl-1-piperazinyl) phenyl]-2-(2-chlorophenoxy) acetamide on Osteoclast Differentiation In Vitro via the Downregulation of TRAF6

2019 ◽  
Vol 20 (20) ◽  
pp. 5196 ◽  
Author(s):  
Zhihao Chen ◽  
Eunjin Cho ◽  
Jinkyung Lee ◽  
Sunwoo Lee ◽  
Tae-Hoon Lee
Keyword(s):  
Bone Resorption ◽  
Mononuclear Cells ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Marker Genes ◽  
Tartrate Resistant Acid Phosphatase ◽  
Specific Marker ◽  
Potential Candidate ◽  
Dependent Manner

Osteoclasts are poly-nuclear cells that resorb mineral components from old or damaged bone tissue. Primary mononuclear cells are activated by receptor activator of nuclear factor kappa-Β ligand (RANKL) and differentiate into large multinucleated cells. Dysregulation of osteoclast differentiation can lead to pathological bone loss and destruction. Many studies have focused on the development of new molecules to regulate RANKL-mediated signaling. In this study, N-[2-(4-acetyl-1-piperazinyl)phenyl]-2-(2-chlorophenoxy) acetamide (PPOA-N-Ac-2-Cl) led to a significant decrease in the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells in a dose-dependent manner, without inducing significant cytotoxicity. PPOA-N-Ac-2-Cl affected the expression of osteoclast-specific marker genes, such as TRAF6, c-fos, DC-STAMP, NFATc1, MMP9, CtsK, and TRAP (Acp5), during RANKL-mediated osteoclastogenesis. Moreover, PPOA-N-Ac-2-Cl significantly attenuated the protein levels of CtsK, a critical protease involved in bone resorption. Accordingly, bone resorption activity and F-actin ring formation decreased in the presence of PPOA-N-Ac-2-Cl. In conclusion, this study shows that PPOA-N-Ac-2-Cl acts as an inhibitor of osteoclast differentiation and may serve as a potential candidate agent for the treatment of osteoclast-related bone diseases by virtue of attenuating bone resorption.

scholarly journals XYLOGLUCAN CONJUGATED FUNCTIONALIZED GRAPHENE OXIDE AS A NANO CARRIER SYSTEM FOR pH RESPONSIVE TARGETED DRUG DELIVERY OF FUCOIDAN

2021 ◽  
pp. 144-153
Author(s):  
K. SONIA ◽  
D. RAJESH ◽  
S. ARUNA SHARMILI ◽  
K. S. MEENA
Keyword(s):  
Drug Delivery ◽  
Graphene Oxide ◽  
Hemolytic Activity ◽  
Targeted Delivery ◽  
Drug Loading ◽  
Potential Candidate ◽  
Functionalized Graphene ◽  
Ph Responsive ◽  
Functionalized Graphene Oxide

Objective: Marine polysaccharides are materializing in the field of biomedicine owing to its promising properties, including high biocompatibility, excellent biodegradability, nontoxic nature, abundance and low cost. Fucoidan (FU), a sulphated marine polysaccharide extracted from brown seaweed, shows a promising application prospect as an anticancer model drug. In order to enhance the stability, biocompatibility and drug loading capacity, xyloglucan was chosen as a targeting ligand, conjugated onto the surface of chitosan functionalized graphene oxide for targeted delivery of fucoidan. Methods: Firstly, Graphene oxide (GO) was prepared by modified Hummer’s method and functionalized with chitosan (CS) via amidation process, further conjugated with xyloglucan (XG). The resulting conjugate, GO-CS-XG, was used to deliver fucoidan through a nanocarrier drug delivery method. The developed GO-CS-XG-FU nanosystem was analyzed for its physiochemical characterization, morphology, hemolytic activity, anti-inflammatory and anticancer activity. Results: The FU loading efficiency and capacity were 75.7% and 83.4%, respectively. XG ligands on the nanoparticle may lead the nanoparticles to actively target cancer cells. Hemolytic activity of the FU-loaded GO-CS-XG nanosystem shows negligible activity, thus making it a potential candidate for biomedical applications. In vitro drug release analysis of FU from GO-CS-XG was lesser at physiological pH but under acidic conditions, it was significantly increased. Results of in vitro cell viability studies indicate that the efficiency of fucoidan was improved upon conjugation with the nanosystem (GO-CS-XG) against human histiocytic lymphoma (U 937) cell line. Conclusion: As a result, we propose a new multifunctional graphene-based targeted platform by using xyloglucan polysaccharide as targeting nanomaterial for pH-responsive anticancer drug delivery with high efficacy.

scholarly journals Conducting PEEK Nanocomposites with Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multi-Modal Therapeutic Applications

2020 ◽  
Author(s):  
Miaomiao He ◽  
Ce zhu ◽  
Huan Xu ◽  
dan Sun ◽  
Chen Chen ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Repair ◽  
Graphene Nanosheets ◽  
Biomechanical Properties ◽  
Bone Diseases ◽  
Bone Tissue Regeneration ◽  
Order Of Magnitude

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades due to its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue towards its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Due to the formation of electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved twelve order of magnitude enhancement in its electrical conductivity, and have enabled electrophoretic deposition of bioactive/anti-bacterial coating consisting of stearyltrimethylammonium chloride (STAC) modified hydroxyapatite (HA). The coated composite implant showed significant boosting of BMSC cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers have enabled laser induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 oC in 150 s. The unique multi-functionality of our composite implant has also been demonstrated for photothermal applications such as enhancing bacterial (E. coli and S. aureus) eradication and tumor cell (MG63) inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multi-functional implant in bone repair applications as well as multi-modal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis

Design and Charecterization of Anticancer Engineered Resealed Erythrocytes

1970 ◽  
Vol 1 (3) ◽  
pp. 243-250
Author(s):  
R. C. Doijad ◽  
N. V. Deshmukh ◽  
D. S. Bhambere ◽  
Rony Joseph ◽  
F. V. Manvi
Keyword(s):  
Targeted Delivery ◽  
Release Kinetics ◽  
Reticuloendothelial System ◽  
Sem Analysis ◽  
In Vitro Tests ◽  
Mean Corpuscular Hemoglobin ◽  
Laser Scattering ◽  
Zero Order Kinetics ◽  
Model Drug

A number of investigators have been focusing their attention on the encapsulation of antineoplastic drugs within erythrocytes to diminish their side effects. In this study, human erythrocytes have been loaded by methotrexate (MTX) as a model drug using hypotonic hemolysis method for targeted delivery of this drug. A series of in vitro tests have been carried out to characterize the carrier cells in vitro, including loading parameters, hemoglobin release kinetics, particle size distribution, SEM analysis, osmotic and turbulence fragilities. Carrier erythrocytes having acceptable loading parameters, released their drug content according to zero-order kinetics. Mean corpuscular hemoglobin content values of the cells decreased, the apparent cell sizes measured using dynamic laser scattering, were not significantly different from normal erythrocytes, but the real sizes, measured using SEM, and surface topologies were quite different between loaded and unloaded cells. The MTX-loaded cells were remarkably more fragile compared to the normal cells. Drug loaded erythrocytes showed preferential drug targeting to liver followed by lungs, kidney and spleen. Totally, MTX-loaded erythrocytes seem to be a promising delivery system for targeting the drug to reticuloendothelial system (RES).

scholarly journals Preparation and Evaluation of Ornidazole Periodontal Films

2016 ◽  
Vol 19 (2) ◽  
pp. 133-146 ◽  
Author(s):  
Jayera Islam Urmi ◽  
Marzia Alam ◽  
Md Saiful Islam Pathan
Keyword(s):  
Targeted Delivery ◽  
Release Kinetics ◽  
Minimum Weight ◽  
Moisture Loss ◽  
Content Uniformity ◽  
Total Solid Content ◽  
Surface Ph ◽  
Weight Variation ◽  
Folding Endurance

Periodontitis is a local infection in the gingival crevices, which affects the structural organs surrounding the teeth like periodontal ligament, connective tissue and bone. Ornidazole is an antimicrobial drug widely used to treat periodontitis. The primary objective of this study was to design and evaluate periodontal films of ornidazole for placement into the periodontal pockets for targeted delivery of drug. Nine formulations (F1 to F9) were prepared by solvent casting method using polymer A, polymer B and plasticizer A. Chloroform and dichloromethane were used as solvent system. The API and dental films were then evaluated for various parameters including trinocular microscopic image, melting point, weight variation, thickness, folding endurance, surface pH, swelling index, percentage moisture loss, antimicrobial activity, content uniformity, in vitro drug release and release kinetics as well as RTIR and DSC. Formulation F1 showed the minimum weight and thickness and F9 showed the maximum. It was observed that weight and thickness of film were directly proportional to the total solid content of the film. RSDs of content uniformity test for all the batches were below 3.0%. Folding endurance and swelling index of films were inversely proportional to the amount of polymer in the film. The surface pH of all the batches were between 6-7. Formulation F1 revealed the maximum percentage of moisture loss (19.34%), while F8 showed the minimum (3.654%). Formulation F2 demonstrated data the highest zone of inhibition (21.91 mm).Bangladesh Pharmaceutical Journal 19(2): 133-146, 2016

scholarly journals BMP-2 Grafted nHA/PLGA Hybrid Nanofiber Scaffold Stimulates Osteoblastic Cells Growth

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Adnan Haider ◽  
Sukyoung Kim ◽  
Man-Woo Huh ◽  
Inn-Kyu Kang
Keyword(s):  
Targeted Delivery ◽  
Bone Tissue Regeneration ◽  
Osteoblastic Cells ◽  
Osteoblastic Cell ◽  
Spectroscopic Techniques ◽  
Nanofiber Scaffold ◽  
Morphogenetic Protein ◽  
Nanofiber Scaffolds ◽  
Hybrid Nanofiber

Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/degenerated tissues or organs. Natural bone is a hierarchical structure, comprised of various cells having specific functions that are regulated by sophisticated mechanisms. However, the regulation of the normal functions in damaged or injured cells is disrupted. In order to address this problem, we attempted to artificially generate a scaffold for mimicking the characteristics of the extracellular matrix at the nanoscale level to trigger osteoblastic cell growth. For this purpose, we have chemically grafted bone morphogenetic protein (BMP-2) onto the surface of L-glutamic acid modified hydroxyapatite incorporated into the PLGA nanofiber matrix. After extensive characterization using various spectroscopic techniques, the BMP-g-nHA/PLGA hybrid nanofiber scaffolds were subjected to variousin vitrocytocompatibility tests. The results indicated that BMP-2 on BMP-g-nHA/PLGA hybrid nanofiber scaffolds greatly stimulated osteoblastic cells growth, contrary to the nHA/PLGA and pristine PLGA nanofiber scaffold, which are used as control. These results suggest that BMP-g-nHA/PLGA hybrid nanofiber scaffold can be used as a nanodrug carrier for the controlled and targeted delivery of BMP-2, which will open new possibilities for enhancing bone tissue regeneration and will help in the treatment of various bone-related diseases in the future.

scholarly journals Promotion of Bone Regeneration Using Bioinspired PLGA/MH/ECM Scaffold Combined with Bioactive PDRN

Materials ◽  
2021 ◽  
Vol 14 (15) ◽  
pp. 4149
Author(s):  
Da-Seul Kim ◽  
Jun-Kyu Lee ◽  
Ji-Won Jung ◽  
Seung-Woon Baek ◽  
Jun Hyuk Kim ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Bone Repair ◽  
Bone Defects ◽  
Biological Properties ◽  
Bone Tissue Regeneration ◽  
Inflammatory Factors ◽  
Potential Candidate ◽  
Gene Expressions ◽  
Marrow Mesenchymal Stem Cells

Current approaches of biomaterials for the repair of critical-sized bone defects still require immense effort to overcome numerous obstacles. The biodegradable polymer-based scaffolds have been required to expand further function for bone tissue engineering. Poly(lactic-co-glycolic) acid (PLGA) is one of the most common biopolymers owing to its biodegradability for tissue regenerations. However, there are major clinical challenges that the byproducts of the PLGA cause an acidic environment of implanting site. The critical processes in bone repair are osteogenesis, angiogenesis, and inhibition of excessive osteoclastogenesis. In this study, the porous PLGA (P) scaffold was combined with magnesium hydroxide (MH, M) and bone-extracellular matrix (bECM, E) to improve anti-inflammatory ability and osteoconductivity. Additionally, the bioactive polydeoxyribonucleotide (PDRN, P) was additionally incorporated in the existing PME scaffold. The prepared PMEP scaffold has pro-osteogenic and pro-angiogenic effects and inhibition of osteoclast due to the PDRN, which interacts with the adenosine A2A receptor agonist that up-regulates expression of vascular endothelial growth factor (VEGF) and down-regulates inflammatory cytokines. The PMEP scaffold has superior biological properties for human bone-marrow mesenchymal stem cells (hBMSCs) adhesion, proliferation, and osteogenic differentiation in vitro. Moreover, the gene expressions related to osteogenesis and angiogenesis of hBMSCs increased and the inflammatory factors decreased on the PMEP scaffold. In conclusion, it provides a promising strategy and clinical potential candidate for bone tissue regeneration and repairing bone defects.

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