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Drug Delivery Applications of Nanomaterials for Bone Diseases and Bone...
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Drug Delivery Applications of Nanomaterials for Bone Diseases and Bone Regeneration

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (10 June 2021) | Viewed by 22190

Special Issue Editor

Dr. Simona Sapino

E-Mail Website
Guest Editor
Department of Drug Science and Technology, University of Torino, 10125 Turin, Italy
Interests: lipid nanoparticles; microemulsions; ophthalmic therapeutics; anticancer therapy; retinal diseases; combinational therapies; in vitro preclinical models; veterinary medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Many drug classes have been developed in order to treat bone diseases and to promote bone regeneration. Among all, bisphosphonates, antibiotics, monoclonal antibodies, calcitonin and estrogen agonists/antagonists are the most used, although they exhibit several adverse reactions. For this reason, the treatment of bone diseases needs to be improved. In last years, many efforts have been focused on the development of systems able to pass the blood-bone marrow barrier, to release drugs in a controlled manner and to mimic bone structure.

The best results were obtained in the field of nanosystems, that include nanoparticles, scaffolds, hydrogels and cements, composed of different materials (from polymers to ceramics). They exhibit less invasive injections procedures than traditional one and allow improved delivery efficiency. Although many gaps are still present, the extraordinary properties of nanomaterials will open up promising avenues to prevent and treat bone diseases and to promote bone regeneration.

This Special Issue makes a point on the current state-of-the-art, highlighting current progress in nanomaterials for bone targeted drugs.

Dr. Simona Sapino
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nanomaterials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Bone diseases
  • bone regeneration
  • nanosystems
  • drug controlled release

Published Papers (6 papers)

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Research

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17 pages, 3923 KiB  
Article
Calcium Phosphate-Coated Lipid Nanoparticles as a Potential Tool in Bone Diseases Therapy
by Simona Sapino, Giulia Chindamo, Daniela Chirio, Maela Manzoli, Elena Peira, Chiara Riganti and Marina Gallarate
Nanomaterials 2021, 11(11), 2983; https://doi.org/10.3390/nano11112983 - 06 Nov 2021
Cited by 11 | Viewed by 2021
Abstract
The treatment of bone diseases (including osteoporosis, osteoarthritis, and bone cancer) often results in reduced efficiency and/or adverse reactions due to the fact that it is not specifically targeted to the site of action. The employment of a suitable carrier should increase drug [...] Read more.
The treatment of bone diseases (including osteoporosis, osteoarthritis, and bone cancer) often results in reduced efficiency and/or adverse reactions due to the fact that it is not specifically targeted to the site of action. The employment of a suitable carrier should increase drug location to the site of bone disease. The purpose of this study is to prepare and characterize lipid nanoparticles (NPs) coated with calcium phosphate (CaP-NPs). A coating method, to date used only to obtain liposomes covered with CaP, is herein partially-modified to prepare CaP-coated lipid NPs. An extensive physico-chemical characterization was achieved by employing several techniques (DLS, SEM and TEM, and both combined with EDS, XRD, and FTIR) that confirmed the feasibility of the developed coating method. Preliminary uptake studies on human osteosarcoma cells (U-2OS) were performed by entrapping, as a lipid probe, Sudan Red III in NPs. The obtained data provided evidence that CaP-NPs showed higher cell accumulation than uncoated NPs. This result may have important implications for the development of drug loaded CaP-NPs to be tested in vitro with a view of planning future treatment of bone diseases, and indicate that CaP-NPs are potential vehicles for selective drug delivery to bone tissue. Full article
(This article belongs to the Special Issue Drug Delivery Applications of Nanomaterials for Bone Diseases and Bone Regeneration)
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12 pages, 2563 KiB  
Article
Multifunctional Tannic Acid-Alendronate Nanocomplexes with Antioxidant, Anti-Inflammatory, and Osteogenic Potency
by Somang Choi, Han-Saem Jo, Heegyeong Song, Hak-Jun Kim, Jong-Keon Oh, Jae-Woo Cho, Kyeongsoon Park and Sung-Eun Kim
Nanomaterials 2021, 11(7), 1812; https://doi.org/10.3390/nano11071812 - 13 Jul 2021
Cited by 13 | Viewed by 2754
Abstract
In the current study, we fabricated tannic acid-alendronate (TA-ALN) nanocomplexes (NPXs) via self-assembly. These TA-ALNs were characterized by dynamic light scattering, zeta potential, transmission electron microscopy, and FT-IR spectroscopy. The TA-ALNs were evaluated for antioxidant, anti-inflammatory, and osteogenesis-accelerating abilities in osteoblast-like cells (MC3T3-E1 [...] Read more.
In the current study, we fabricated tannic acid-alendronate (TA-ALN) nanocomplexes (NPXs) via self-assembly. These TA-ALNs were characterized by dynamic light scattering, zeta potential, transmission electron microscopy, and FT-IR spectroscopy. The TA-ALNs were evaluated for antioxidant, anti-inflammatory, and osteogenesis-accelerating abilities in osteoblast-like cells (MC3T3-E1 cells). All TA-ALNs displayed nano-sized beads that were circular in form. Treatment with TA-ALN (1:0.1) efficiently removed reactive oxygen species in cells and protected osteoblast-like cells from toxic hydrogen peroxide conditions. Moreover, TA-ALN (1:0.1) could markedly decrease the mRNA levels of pro-inflammatory mediators in lipopolysaccharide-stimulated cells. Furthermore, cells treated with TA-ALN (1:1) exhibited not only significantly greater alkaline phosphatase activity and calcium collection, but also outstandingly higher mRNA levels of osteogenesis-related elements such as collagen type I and osteocalcin. These outcomes indicate that the prepared TA-ALNs are excellent for antioxidant, anti-inflammatory, and osteogenic acceleration. Accordingly, TA-ALN can be used latently for bone renovation and regeneration in people with bone fractures, diseases, or disorders. Full article
(This article belongs to the Special Issue Drug Delivery Applications of Nanomaterials for Bone Diseases and Bone Regeneration)
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Review

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39 pages, 6012 KiB  
Review
Anodic TiO2 Nanotubes: Tailoring Osteoinduction via Drug Delivery
by Jung Park, Anisoara Cimpean, Alexander B. Tesler and Anca Mazare
Nanomaterials 2021, 11(9), 2359; https://doi.org/10.3390/nano11092359 - 11 Sep 2021
Cited by 25 | Viewed by 3763
Abstract
TiO2 nanostructures and more specifically nanotubes have gained significant attention in biomedical applications, due to their controlled nanoscale topography in the sub-100 nm range, high surface area, chemical resistance, and biocompatibility. Here we review the crucial aspects related to morphology and properties [...] Read more.
TiO2 nanostructures and more specifically nanotubes have gained significant attention in biomedical applications, due to their controlled nanoscale topography in the sub-100 nm range, high surface area, chemical resistance, and biocompatibility. Here we review the crucial aspects related to morphology and properties of TiO2 nanotubes obtained by electrochemical anodization of titanium for the biomedical field. Following the discussion of TiO2 nanotopographical characterization, the advantages of anodic TiO2 nanotubes will be introduced, such as their high surface area controlled by the morphological parameters (diameter and length), which provides better adsorption/linkage of bioactive molecules. We further discuss the key interactions with bone-related cells including osteoblast and stem cells in in vitro cell culture conditions, thus evaluating the cell response on various nanotubular structures. In addition, the synergistic effects of electrical stimulation on cells for enhancing bone formation combining with the nanoscale environmental cues from nanotopography will be further discussed. The present review also overviews the current state of drug delivery applications using TiO2 nanotubes for increased osseointegration and discusses the advantages, drawbacks, and prospects of drug delivery applications via these anodic TiO2 nanotubes. Full article
(This article belongs to the Special Issue Drug Delivery Applications of Nanomaterials for Bone Diseases and Bone Regeneration)
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23 pages, 1701 KiB  
Review
Nano-Based Biomaterials as Drug Delivery Systems Against Osteoporosis: A Systematic Review of Preclinical and Clinical Evidence
by Francesca Salamanna, Alessandro Gambardella, Deyanira Contartese, Andrea Visani and Milena Fini
Nanomaterials 2021, 11(2), 530; https://doi.org/10.3390/nano11020530 - 19 Feb 2021
Cited by 34 | Viewed by 4059
Abstract
Osteoporosis (OP) is one of the most significant causes of morbidity, particularly in post-menopausal women and older men. Despite its remarkable occurrence, the search for an effective treatment is still an open challenge. Here, we systematically reviewed the preclinical and clinical progress in [...] Read more.
Osteoporosis (OP) is one of the most significant causes of morbidity, particularly in post-menopausal women and older men. Despite its remarkable occurrence, the search for an effective treatment is still an open challenge. Here, we systematically reviewed the preclinical and clinical progress in the development of nano-based materials as drug delivery systems against OP, considering the effects on bone healing and regeneration, the more promising composition and manufacturing methods, and the more hopeful drugs and delivery methods. The results showed that almost all the innovative nano-based delivery systems developed in the last ten years have been assessed by preclinical investigations and are still in the preliminary/early research stages. Our search strategy retrieved only one non-randomized controlled trial (RCT) on oligosaccharide nanomedicine of alginate sodium used for degenerative lumbar diseases in OP patients. Further investigations are mandatory for assessing the clinical translation and commercial purposes of these materials. To date, the main limits for the clinical translation of nano-based materials as drug delivery systems against OP are probably due to the low reproducibility of the manufacturing processes, whose specificity and complexity relies on an adequate chemical, structural, and biomechanical characterization, as the necessary prerequisite before assessing the efficacy of a given treatment or process. Finally, an unsatisfactory drug-loading capacity, an uncontrollable release kinetic, and a low delivery efficiency also limit the clinical application. Full article
(This article belongs to the Special Issue Drug Delivery Applications of Nanomaterials for Bone Diseases and Bone Regeneration)
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35 pages, 2418 KiB  
Review
Bone Diseases: Current Approach and Future Perspectives in Drug Delivery Systems for Bone Targeted Therapeutics
by Giulia Chindamo, Simona Sapino, Elena Peira, Daniela Chirio, Mónica Cristina Gonzalez and Marina Gallarate
Nanomaterials 2020, 10(5), 875; https://doi.org/10.3390/nano10050875 - 01 May 2020
Cited by 64 | Viewed by 5165
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue Drug Delivery Applications of Nanomaterials for Bone Diseases and Bone Regeneration)
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Other

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16 pages, 622 KiB  
Systematic Review
Nano-Hydroxyapatite as a Delivery System for Promoting Bone Regeneration In Vivo: A Systematic Review
by Anis Syauqina Mohd Zaffarin, Shiow-Fern Ng, Min Hwei Ng, Haniza Hassan and Ekram Alias
Nanomaterials 2021, 11(10), 2569; https://doi.org/10.3390/nano11102569 - 29 Sep 2021
Cited by 26 | Viewed by 3538
Abstract
Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal [...] Read more.
Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal to no toxicity or inflammatory response. This systematic review aims to provide an appraisal of the effectiveness of nHA as a delivery system for bone regeneration and whether the conjugation of proteins, antibiotics, or other bioactive molecules to the nHA further enhances osteogenesis in vivo. Out of 282 articles obtained from the literature search, only 14 articles met the inclusion criteria for this review. These studies showed that nHA was able to induce bone regeneration in various animal models with large or critical-sized bone defects, open fracture, or methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. The conjugations of drugs or bioactive molecules such as bone-morphogenetic protein-2 (BMP-2), vancomycin, calcitriol, dexamethasone, and cisplatin were able to enhance the osteogenic property of nHA. Thus, nHA is a promising delivery system for a variety of compounds in promoting bone regeneration in vivo. Full article
(This article belongs to the Special Issue Drug Delivery Applications of Nanomaterials for Bone Diseases and Bone Regeneration)
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