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6.9
5.4
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Pharmaceutics
Special Issues
Bone Targeted Drug Delivery
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Bone Targeted Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (31 January 2019) | Viewed by 45116

Special Issue Editors

Prof. Danielle S. W. Benoit

E-Mail Website
Guest Editor
Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA
Interests: therapeutic biomaterials; nanomaterials; bone-targeted drug delivery; bone regeneration; tissue engineering
Dr. Yuchen Wang

E-Mail Website
Guest Editor
Product Development Scientist, PaxVax, Inc., USA
Interests: controlled drug delivery; nanotechnology; biomaterials; hydrogel fabrication; bone targeted drug delivery

Special Issue Information

Dear Colleagues,

As a result of greatly improved understanding of bone biology, many drug classes have been identified to treat a variety of bone diseases, including osteoporosis, bone metastases, osteomyelitis, and to improve fracture healing. However, very few of these interventions are specific to bone. Moreover, most drugs have very low distribution (<1%) to bone after systemic administration. A lack of bone specificity and biodistribution lowers the clinical potential of these therapeutic agents and can lead to serious complications due to off-target effects, as best highlighted by hormone replacement therapy. By incorporating bone-targeting mechanisms either directly to drugs or within drug delivery systems, pharmacokinetic profiles can be dramatically altered to favor skeletal delivery. This is exemplified by bisphosphonate drugs, which specifically bind to calcium present within bone hydroxyapatite. However, due to pan-skeleton biodistribution of hydroxyapatite-targeted drug delivery systems, the development of delivery systems with enhanced specificity for druggable sites within the skeleton represents a great challenge in the field of controlled drug targeting and delivery.

This Special Issue has the aim of highlighting current progress in new therapeutic approaches for bone targeting of drugs.

Prof. Danielle S. W. Benoit
Dr. Yuchen Wang
Guest Editors

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. Pharmaceutics is an international peer-reviewed open access monthly 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 targeting
  • Bone regeneration
  • Therapeutic materials
  • Targeted drug delivery
  • Nanoparticles
  • Microspheres
  • Fracture healing
  • Osteomyelitis
  • Osteosarcoma
  • Bone metastasis
  • Osteoporosis

Published Papers (5 papers)

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Research

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21 pages, 3478 KiB  
Article
Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis
by Ryan P. Trombetta, Mark J. Ninomiya, Ihab M. El-Atawneh, Emma K. Knapp, Karen L. de Mesy Bentley, Paul M. Dunman, Edward M. Schwarz, Stephen L. Kates and Hani A. Awad
Pharmaceutics 2019, 11(2), 94; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11020094 - 22 Feb 2019
Cited by 27 | Viewed by 4572
Abstract
Osteomyelitis is a chronic bone infection that is often treated with adjuvant antibiotic-impregnated poly(methyl methacrylate) (PMMA) cement spacers in multi-staged revisions. However, failure rates remain substantial due to recurrence of infection, which is attributed to the poor performance of the PMMA cement as [...] Read more.
Osteomyelitis is a chronic bone infection that is often treated with adjuvant antibiotic-impregnated poly(methyl methacrylate) (PMMA) cement spacers in multi-staged revisions. However, failure rates remain substantial due to recurrence of infection, which is attributed to the poor performance of the PMMA cement as a drug release device. Hence, the objective of this study was to design and evaluate a bioresorbable calcium phosphate scaffold (CaPS) for sustained antimicrobial drug release and investigate its efficacy in a murine model of femoral implant-associated osteomyelitis. Incorporating rifampin and sitafloxacin, which are effective against bacterial phenotypes responsible for bacterial persistence, into 3D-printed CaPS coated with poly(lactic co-glycolic) acid, achieved controlled release for up to two weeks. Implantation into the murine infection model resulted in decreased bacterial colonization rates at 3- and 10-weeks post-revision for the 3D printed CaPS in comparison to gentamicin-laden PMMA. Furthermore, a significant increase in bone formation was observed for 3D printed CaPS incorporated with rifampin at 3 and 10 weeks. The results of this study demonstrate that osteoconductive 3D printed CaPS incorporated with antimicrobials demonstrate more efficacious bacterial colonization outcomes and bone growth in a single-stage revision in comparison to gentamicin-laden PMMA requiring a two-stage revision. Full article
(This article belongs to the Special Issue Bone Targeted Drug Delivery)
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13 pages, 1626 KiB  
Article
Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice
by Hua Wang, Lifeng Xiao, Jianguo Tao, Venkat Srinivasan, Brendan F. Boyce, Frank H. Ebetino, Babatunde O. Oyajobi, Robert K. Boeckman, Jr. and Lianping Xing
Pharmaceutics 2018, 10(3), 154; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10030154 - 10 Sep 2018
Cited by 29 | Viewed by 5111
Abstract
Multiple myeloma (MM) is the most common cancer affecting the bone and bone marrow and remains incurable for most patients; novel therapies are therefore needed. Bortezomib (Btz) is an FDA-approved drug for the treatment of patients with MM. However, its severe side effects [...] Read more.
Multiple myeloma (MM) is the most common cancer affecting the bone and bone marrow and remains incurable for most patients; novel therapies are therefore needed. Bortezomib (Btz) is an FDA-approved drug for the treatment of patients with MM. However, its severe side effects require a dose reduction or the potential discontinuation of treatment. To overcome this limitation, we conjugated Btz to a bisphosphonate (BP) residue lacking anti-osteoclastic activity using a novel chemical linker and generated a new bone-targeted Btz-based (BP-Btz) proteasome inhibitor. We demonstrated that BP-Btz, but not Btz, bound to bone slices and inhibited the growth of MM cells in vitro. In a mouse model of MM, BP-Btz more effectively reduced tumor burden and bone loss with less systemic side effects than Btz. Thus, BP-Btz may represent a novel therapeutic approach to treat patients with MM. Full article
(This article belongs to the Special Issue Bone Targeted Drug Delivery)
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Review

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21 pages, 1804 KiB  
Review
Targeted Nanomedicine to Treat Bone Metastasis
by Isaac M. Adjei, Madison N. Temples, Shannon B. Brown and Blanka Sharma
Pharmaceutics 2018, 10(4), 205; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040205 - 25 Oct 2018
Cited by 41 | Viewed by 22225
Abstract
Bone metastases are common complications of solid tumors, particularly those of the prostate, breast, and lungs. Bone metastases can lead to painful and devastating skeletal-related events (SREs), such as pathological fractures and nerve compressions. Despite advances in treatment for cancers in general, options [...] Read more.
Bone metastases are common complications of solid tumors, particularly those of the prostate, breast, and lungs. Bone metastases can lead to painful and devastating skeletal-related events (SREs), such as pathological fractures and nerve compressions. Despite advances in treatment for cancers in general, options for bone metastases remain inadequate and generally palliative. Anticancer drugs (chemotherapy and radiopharmaceuticals) do not achieve therapeutic concentrations in the bone and are associated with dose-limiting side effects to healthy tissues. Nanomedicines, with their tunable characteristics, have the potential to improve drug targeting to bone metastases while decreasing side effects for their effective treatment. In this review, we present the current state of the art for nanomedicines to treat bone metastases. We also discuss new treatment modalities enhanced by nanomedicine and their effects on SREs and disease progression. Full article
(This article belongs to the Special Issue Bone Targeted Drug Delivery)
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22 pages, 691 KiB  
Review
Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies
by Sonia Vallet, Julia-Marie Filzmoser, Martin Pecherstorfer and Klaus Podar
Pharmaceutics 2018, 10(4), 202; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040202 - 24 Oct 2018
Cited by 29 | Viewed by 5227
Abstract
Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients’ quality of life and, ultimately, survival. During [...] Read more.
Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients’ quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the mainstay to prevent skeletal-related events in MM for almost two decades. Excitingly, the most recent approval of the receptor activator of NF-kappa B ligand (RANKL) inhibitor, denosumab, expanded treatment options for MBD, for patients with compromised renal function, in particular. In addition, several other bone-targeting agents, including bone anabolic drugs, are currently in preclinical and early clinical assessment. This review summarizes our up-to-date knowledge on the pathogenesis of MBD and discusses novel state-of-the-art treatment strategies that are likely to enter clinical practice in the near future. Full article
(This article belongs to the Special Issue Bone Targeted Drug Delivery)
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26 pages, 1125 KiB  
Review
Scaffolds as Structural Tools for Bone-Targeted Drug Delivery
by Riccardo Ferracini, Isabel Martínez Herreros, Antonio Russo, Tommaso Casalini, Filippo Rossi and Giuseppe Perale
Pharmaceutics 2018, 10(3), 122; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10030122 - 08 Aug 2018
Cited by 49 | Viewed by 7079
Abstract
Although bone has a high potential to regenerate itself after damage and injury, the efficacious repair of large bone defects resulting from resection, trauma or non-union fractures still requires the implantation of bone grafts. Materials science, in conjunction with biotechnology, can satisfy these [...] Read more.
Although bone has a high potential to regenerate itself after damage and injury, the efficacious repair of large bone defects resulting from resection, trauma or non-union fractures still requires the implantation of bone grafts. Materials science, in conjunction with biotechnology, can satisfy these needs by developing artificial bones, synthetic substitutes and organ implants. In particular, recent advances in materials science have provided several innovations, underlying the increasing importance of biomaterials in this field. To address the increasing need for improved bone substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from organic or inorganic materials, incorporating drugs and growth factors, to induce new bone tissue formation. This review emphasizes recent progress in materials science that allows reliable scaffolds to be synthesized for targeted drug delivery in bone regeneration, also with respect to past directions no longer considered promising. A general overview concerning modeling approaches suitable for the discussed systems is also provided. Full article
(This article belongs to the Special Issue Bone Targeted Drug Delivery)
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