Adsorption of Alendronate onto Biomimetic Apatite Nanocrystals to Develop Drug Carrier Coating for Bone Implants

2012 ◽  
Vol 529-530 ◽  
pp. 475-479 ◽  
Author(s):  
Ruggero Bosco ◽  
Michele Iafisco ◽  
Jeroen van den Beucken ◽  
Sander C.G. Leeuwenburgh ◽  
John A. Jansen
Keyword(s):  
Drug Delivery ◽  
Surface Engineering ◽  
Drug Carrier ◽  
Local Treatment ◽  
Titanium Implants ◽  
Bone Implants ◽  
Bone Implant ◽  
Biomimetic Apatite

The possibility to develop a bone implant with bioactive aspects and in situ drug-delivery properties, in order to provide local treatment in vivo, is a big challenge. Where conventional surface modifications for bone implants focused on the deposition of ceramic (mostly calcium phosphate, CaP) coatings, current surface engineering approaches attempt to incorporate active features to render bone implant surfaces capable to direct biological performance. Biomimetic apatite nanocrystals (nAp) represent, among the CaPs, an elective material for bone applications and their surface functionalization with drugs allows them to act as a drug-delivery vehicle. Since load-bearing bone implants are increasingly used in patients with compromised health conditions, surface engineering is important to warrant the performance of these implants under such conditions. In view of this, bisphosphonates (BPs) represent a treatment modality for a variety of disorders of bone metabolism associated to bone loss, including Paget's bone disease, osteoporosis, fibrous dysplasia and bone metastases. In this work, we have synthesized and characterized bioinspired nAp and evaluated their functionalization with alendronate. In vitro tests will be used to evaluate the efficacy of the functionalized compound to impede the formation of osteoclasts and to show that alendronate-functionalized nAp can significantly reduce osteoclasteogenesis. Finally, alendronate-functionalized nAp (FnAp) has been deposited on titanium implants via the electrospray deposition technique in order to develop inorganic-organic coatings for bone implants with improved functionality.

scholarly journals Albumin coated liposomes: a novel platform for macrophage specific drug delivery

2011 ◽  
Vol 1 (1) ◽  
pp. 2 ◽  
Author(s):  
Clément Vuarchey ◽  
Sushil Kumar ◽  
Reto Schwendener
Keyword(s):  
Drug Delivery ◽  
Drug Carrier ◽  
Cell Types ◽  
Specific Drug ◽  
Splenic Macrophages ◽  
Peg Liposomes ◽  
Short Time ◽  
Liposome Surface

Here we report a new and efficient approach of macrophage specific drug delivery by coating liposomes with albumin. Activated albumin was reacted with liposomes containing polyethylene glycol (PEG) as hydrophilic spacers to create a flexible layer of covalently bound albumin molecules on the liposome surface. Albumin coated liposomes were taken up faster and more efficiently than uncoated liposomes by murine macrophages. Liposome uptake was significantly higher in macropha - ges as compared to other cell types tested (endothelial cells, fibroblasts, tumor cells), suggesting specificity for macrophages. In vivo, splenic macrophages phagocytosed BSA coated liposomes (BSA-L) at faster rates compared to conventional liposomes (L) and PEG liposomes (PEG-L). To prove the effectiveness of this new macrophage specific drug carrier, the bisphosphonates clodronate and zoledronate were encapsulated in BSA-L and compared with conventional liposomes. <em>In vitro</em>, treatment of macrophages with clodronate or zoledronate in BSA-L led to cytotoxic activity within a very short time and to up to 50-fold reduced IC50 concentrations. <em>In vivo</em>, clodronate encapsulated in BSA-L depleted splenic macrophages at a 5-fold lower concentration as conventional clodronate-liposomes. Our results highlight the pharmaceutical benefits of albumin-coated liposomes for macrophage specific drug delivery.

PLA/PLGA nanoparticles for delivery of drugs across the blood-brain barrier

2013 ◽  
Vol 2 (3) ◽  
pp. 241-257 ◽  
Author(s):  
Jingyan Li ◽  
Cristina Sabliov
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Drug Carrier ◽  
Plga Nanoparticles ◽  
Brain Barrier ◽  
Poly Lactic Acid ◽  
Blood Brain

AbstractThe blood-brain barrier (BBB), which protects the central nervous system (CNS) from unnecessary substances, is a challenging obstacle in the treatment of CNS disease. Many therapeutic agents such as hydrophilic and macromolecular drugs cannot overcome the BBB. One promising solution is the employment of polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs as drug carrier. Over the past few years, significant breakthroughs have been made in developing suitable PLGA and poly (lactic acid) (PLA) NPs for drug delivery across the BBB. Recent advances on PLGA/PLA NPs enhanced neural delivery of drugs are reviewed in this paper. Both in vitro and in vivo studies are included. In these papers, enhanced cellular uptake and therapeutic efficacy of drugs delivered with modified PLGA/PLA NPs compared with free drugs or drugs delivered by unmodified PLGA/PLA NPs were shown; no significant in vitro cytotoxicity was observed for PLGA/PLA NPs. Surface modification of PLGA/PLA NPs by coating with surfactants/polymers or covalently conjugating the NPs with targeting ligands has been confirmed to enhance drug delivery across the BBB. Most unmodified PLGA NPs showed low brain uptake (<1%), which indirectly confirms the safety of PLGA/PLA NPs used for other purposes than treating CNS diseases.

scholarly journals Engineering Immunomodulatory and Osteoinductive Implant Surfaces via Mussel Adhesion-Mediated Ion Coordination and Molecular Clicking

2021 ◽  
Author(s):  
Tao Wang ◽  
Jiaxiang Bai ◽  
Min Lu ◽  
Chenglong Huang ◽  
Dechun Geng ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Immunomodulatory Activity ◽  
Tissue Formation ◽  
Surface Adhesion ◽  
Bone Implants ◽  
Dual Effect ◽  
Bone Implant ◽  
New Ideas

Abstract Immune action and new tissue formation are two distinct but overlapping stages involved in tissue regeneration process. However, current biomaterial design is trapped into a one-sided consideration with either focusing on the regulation of immune response or paying attention to induction of new tissue formation. Bone implants also face the same problem. In this work, we designed a dual-effect bone implant with immunomodulatory activity with direct osteogenicity by a mussel adhesion-mediated ion coordination and molecular clicking strategy. The mussel-inspired chemistry for surface adhesion, bioclickable way for molecular conjugation, and coordination means for ion loading led to an immunoactive Zn2+ ion and osteoinductive BMP-2 peptide co-modified coating on bone implants. We demonstrated that the dual-effect coating could better improve cytocompatibility and promote the polarization of macrophages to M2 phenotype in vitro and in vivo. Moreover, the Zn2+ ion and BMP-2 peptide co-modified bone implants showed optimal osteogenicity and osseointegration, thus improving implant stability in vivo. We anticipate this study would provide new ideas and solutions for engineering implants with immunoactivity and tissue inductivity to precisely adapt tissue regeneration microenvironment.

scholarly journals Chitosan overlaid Fe3O4/rGO nanocomposite for targeted drug delivery, imaging, and biomedical applications

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Viswanathan Karthika ◽  
Mohamad S. AlSalhi ◽  
Sandhanasamy Devanesan ◽  
Kasi Gopinath ◽  
Ayyakannu Arumugam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Folic Acid ◽  
Targeted Drug Delivery ◽  
Drug Carrier ◽  
Drug Loading ◽  
Antioxidant Properties ◽  
Targeted Drug ◽  
Loading Amount

Abstract A hybrid and straightforward nanosystem that can be used simultaneously for cancer-targeted fluorescence imaging and targeted drug delivery in vitro was reported in this study. A chitosan (CS) polymer coated with reduced graphene oxide (rGO) and implanted with Fe3O4 nanoparticles was fabricated. The fundamental physicochemical properties were confirmed via FT-IR, XRD, FE-SEM, HR-TEM, XPS, and VSM analysis. The in vivo toxicity study in zebrafish showed that the nanocomposite was not toxic. The in vitro drug loading amount was 0.448 mg/mL−1 for doxorubicin, an anticancer therapeutic, in the rGO/Fe3O4/CS nanocomposite. Furthermore, the pH-regulated release was observed using folic acid. Cellular uptake and multimodal imaging revealed the benefit of the folic acid-conjugated nanocomposite as a drug carrier, which remarkably improves the doxorubicin accumulation inside the cancer cells over-express folate receptors. The rGO/Fe3O4/CS nanocomposite showed enhanced antibiofilm and antioxidant properties compared to other materials. This study's outcomes support the use of the nanocomposite in targeted chemotherapy and the potential applications in the polymer, cosmetic, biomedical, and food industries.

scholarly journals Pectin-Based Nanomaterials: Synthesis, Toxicity and Applications

2021 ◽  
Vol 33 (11) ◽  
pp. 2579-2588
Author(s):  
Mandeep Kaur ◽  
Aditya Wadhwa ◽  
Vineet Kumar
Keyword(s):  
Drug Delivery ◽  
Human Body ◽  
Release Kinetics ◽  
Drug Carrier ◽  
Biological Origin ◽  
Nanomaterials Synthesis ◽  
The Stability ◽  
Kinetics Of

Nanomaterials of biological origin are very useful for drug delivery applications. The stability, biodegradability and biocompatibility of pectin nanomaterials in the human body make them an effective drug carrier. This review focus on different aspect of synthesis, drug encapsulation, drug release and safety of pectin-based nanomaterials. The nanomaterials can be used for the delivery of different hydrophilic and hydrophobic drugs to various organs. The release kinetics of drug loaded pectin-based nanoparticles can be studied in vitro as well as in vivo. The pectin-based nanomaterials have good pharmaco-kinetics and can ensure controlled drug delivery. However, the toxicity of pectin-based nanomaterials to human body needs to be evaluated carefully before industrial scale application.

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

In vitro Lipolysis as a Tool for the Establishment of IVIVC for Lipid-Based Drug Delivery Systems

2019 ◽  
Vol 16 (8) ◽  
pp. 688-697
Author(s):  
Ravinder Verma ◽  
Deepak Kaushik
Keyword(s):  
Drug Delivery ◽  
Ph Value ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Rapid Screening ◽  
Resonance Spectroscopy ◽  
Fed State ◽  
In Vitro Lipolysis ◽  
Ph Stat

: In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

scholarly journals Osseointegrating and phase-oriented micro-arc-oxidized titanium dioxide bone implants

2021 ◽  
Vol 19 ◽  
pp. 228080002110068
Author(s):  
Hsien-Te Chen ◽  
Hsin-I Lin ◽  
Chi-Jen Chung ◽  
Chih-Hsin Tang ◽  
Ju-Liang He
Keyword(s):  
Titanium Dioxide ◽  
High Surface ◽  
Cell Activity ◽  
Active Surface ◽  
Rutile Phase ◽  
Hydroxyl Groups ◽  
Bone Implant ◽  
Implant System

Here, we present a bone implant system of phase-oriented titanium dioxide (TiO2) fabricated by the micro-arc oxidation method (MAO) on β-Ti to facilitate improved osseointegration. This (101) rutile-phase-dominant MAO TiO2 (R-TiO2) is biocompatible due to its high surface roughness, bone-mimetic structure, and preferential crystalline orientation. Furthermore, (101) R-TiO2 possesses active and abundant hydroxyl groups that play a significant role in enhancing hydroxyapatite formation and cell adhesion and promote cell activity leading to osseointegration. The implants had been elicited their favorable cellular behavior in vitro in the previous publications; in addition, they exhibit excellent shear strength and promote bone–implant contact, osteogenesis, and tissue formation in vivo. Hence, it can be concluded that this MAO R-TiO2 bone implant system provides a favorable active surface for efficient osseointegration and is suitable for clinical applications.

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