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Novel Strategies for Enhancing the Therapeutic Effect of Bioactive Compounds in the Treatment of Rheumatic Diseases

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (10 May 2022) | Viewed by 18118

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Special Issue Editor

Dr. Mihaela Trif

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Guest Editor

Institute of Biochemistry, Romanian Academy, Bucharest, Romania
Interests: drug delivery systems; nanoparticles cell interaction; liposome technology; in vitro-in vivo models of inflammation; topical, transdermal, intra-articular administration of liposome containing biopharmaceuticals

Special Issue Information

Dear Colleague,

A special interest in the field of nanomedicine is the development of the innovative and efficient nanocarriers with controllable properties for drug delivery and site-specific targeting able to achieve greater efficacy and minimize the toxic effects associated with conventional therapies. The therapeutic profiles of biological and pharmacological agents can be improved by incorporation into nanocarrier systems. Many of them are already approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for use in pharmaceutical products. In the case of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA), nanoparticles containing bioactive compounds can offer tremendous opportunities in diagnosis, monitoring, and treatment. For both conditions, no prevention methods are known, and optimal management is based on early diagnosis. Treatment of irreversible joint damage is achieved through oral, parenteral, or intra-articular drugs administration. The interest in using nanocarriers containing bioproducts from natural sources to treat inflammatory and rheumatic diseases is growing, encouraging researchers to investigate this aspect.

This Special Issue will highlight novel strategies exploring the potential of nanocarriers-based bioproducts of natural origin (included but not limited to vegetal and animal sources), with a focus on rheumatic diseases. Data regarding the design, physico-chemical properties, biocompatibility, anti-inflammatory, and regenerative potential of the pharmaceutical nanoformulations are encouraged. Their performance in vitro and in vivo—especially for local/intra-articular applications (but not limited to these)—and clinical assays are welcome.

Authors are invited to submit original and review articles exploring the therapeutic potential of nanocarriers-based bioproducts, especially for controlled and/or targeted drug delivery applications in rheumatic diseases.

Dr. Mihaela Trif
Guest Editor

Manuscript Submission Information

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Keywords

nanomedicine
rheumatic diseases
osteoarthritis
rheumatoid arthritis
nanoparticles (all materials)
natural bioactive compounds
nanocarriers-based natural bioactive molecules
physical-chemical properties
controlled delivery
therapeutic potential
tissue repair
anti-inflammatory properties
cytokines
local/topical delivery
intra-articular delivery
in vitro assay
in vivo assay

Published Papers (5 papers)

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Research

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16 pages, 2722 KiB

Open AccessArticle

Evaluation of Ruthenium-Based Assemblies as Carriers of Photosensitizers to Treat Rheumatoid Arthritis by Photodynamic Therapy

by Manuel Gallardo-Villagrán, Lucie Paulus, Jean-Louis Charissoux, Sylvain Sutour, Pascale Vergne-Salle, David Yannick Leger, Bertrand Liagre and Bruno Therrien

Pharmaceutics 2021, 13(12), 2104; https://doi.org/10.3390/pharmaceutics13122104 - 07 Dec 2021

Cited by 13 | Viewed by 2563

Abstract

For the first time, ruthenium-based assemblies have been used as carriers for photosensitizers in the treatment of rheumatoid arthritis by photodynamic therapy (PDT). These metallacages are totally soluble in physiological media and can transport photosensitizers (PS) in their cavity. After an incubation period, the PS is released in the cytoplasm and irradiation can take place. This strategy allows photosensitizers with low or null solubility in biological media to be evaluated as PDT agents in rheumatoid arthritis. The systems in which 21H,23H-porphine and 29H,31H-phthalocyanine are encapsulated show excellent photocytotoxicity and no toxicity in the dark. On the other hand, systems in which metalated derivatives such as Mg(II)-porphine and Zn(II)-phthalocyanine are used show good photocytotoxicity, but to a lesser extent than the previous two. Furthermore, the presence of Zn(II)-phthalocyanine significantly increases the toxicity of the system. Overall, fifteen different host–guest systems have been evaluated, and based on the results obtained, they show high potential for treating rheumatoid arthritis by PDT. Full article

(This article belongs to the Special Issue Novel Strategies for Enhancing the Therapeutic Effect of Bioactive Compounds in the Treatment of Rheumatic Diseases)

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17 pages, 1283 KiB

Open AccessArticle

Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain

by Tijn Wiersema, Anna R. Tellegen, Martijn Beukers, Marijn van Stralen, Erik Wouters, Mandy van de Vooren, Nina Woike, George Mihov, Jens C. Thies, Laura B. Creemers, Marianna A. Tryfonidou and Björn P. Meij

Pharmaceutics 2021, 13(8), 1178; https://doi.org/10.3390/pharmaceutics13081178 - 30 Jul 2021

Cited by 9 | Viewed by 2984

Abstract

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs (“placebo”) (n = 10) and evaluated by clinical examination, gait analysis, owners’ questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24–2.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10–3.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study; disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc. Full article

(This article belongs to the Special Issue Novel Strategies for Enhancing the Therapeutic Effect of Bioactive Compounds in the Treatment of Rheumatic Diseases)

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18 pages, 4575 KiB

Open AccessArticle

Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis

by Anna Tellegen, Martijn Beukers, Imke Rudnik-Jansen, Nicolien van Klaveren, Kan Loi How, Nina Woike, George Mihov, Jens Thies, Erik Teske, Laura Creemers, Marianna Tryfonidou and Björn Meij

Pharmaceutics 2021, 13(3), 372; https://doi.org/10.3390/pharmaceutics13030372 - 11 Mar 2021

Cited by 4 | Viewed by 2705

Abstract

Osteoarthritis (OA) is a common cause of pain and disability. Local corticosteroid injections are effective in treating OA pain and inflammation but are short-acting. Prolonged intra-articular (IA) corticosteroid exposure may even lead to cartilage deterioration. The aim of this prospective study was to assess safety and provide proof-of-concept of IA-applied biodegradable polyesteramide-based microspheres (PEAMs) gradually releasing triamcinolone acetonide (TA). Mimicking continuous exposure associated with local drug delivery in canine articular chondrocytes cultured in the continuous presence of TA tissue regeneration was not affected, whereas intermittent exposure reduced proteoglycan production. In this respect, TA-PEAMs administered IA in a proof-of-concept study in 12 client-owned dogs with established OA also showed safety by radiographic examination, without changes in OA severity and in glycosaminoglycan synovial fluid levels. Treatment also resulted in clinical improvement in 10 out of 11 dogs during the two-month follow-up period, which persisted in 6 out of 10 dogs after 6 months, based on objective gait analysis and owner questionnaires. Synovial prostaglandin E₂, a pro-inflammatory marker, was decreased two months after treatment. This study showed safety and proof-of-concept of IA-administered TA-PEAMs in dogs with OA, as a first step towards translation into the veterinary and human clinic. Full article

(This article belongs to the Special Issue Novel Strategies for Enhancing the Therapeutic Effect of Bioactive Compounds in the Treatment of Rheumatic Diseases)

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Review

Jump to: Research

20 pages, 2861 KiB

Open AccessReview

Intra-Articular Drug Delivery for Osteoarthritis Treatment

by Yifeng Cao, Yifeng Ma, Yi Tao, Weifeng Lin and Ping Wang

Pharmaceutics 2021, 13(12), 2166; https://doi.org/10.3390/pharmaceutics13122166 - 15 Dec 2021

Cited by 33 | Viewed by 5353

Abstract

Osteoarthritis (OA) is the most prevalent degenerative joint disease affecting millions of people worldwide. Currently, clinical nonsurgical treatments of OA are only limited to pain relief, anti-inflammation, and viscosupplementation. Developing disease-modifying OA drugs (DMOADs) is highly demanded for the efficient treatment of OA. As OA is a local disease, intra-articular (IA) injection directly delivers drugs to synovial joints, resulting in high-concentration drugs in the joint and reduced side effects, accompanied with traditional oral or topical administrations. However, the injected drugs are rapidly cleaved. By properly designing the drug delivery systems, prolonged retention time and targeting could be obtained. In this review, we summarize the drugs investigated for OA treatment and recent advances in the IA drug delivery systems, including micro- and nano-particles, liposomes, and hydrogels, hoping to provide some information for designing the IA injected formulations. Full article

(This article belongs to the Special Issue Novel Strategies for Enhancing the Therapeutic Effect of Bioactive Compounds in the Treatment of Rheumatic Diseases)

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24 pages, 403 KiB

Open AccessReview

Mechanisms and Pharmaceutical Action of Lipid Nanoformulation of Natural Bioactive Compounds as Efficient Delivery Systems in the Therapy of Osteoarthritis

by Oana Craciunescu, Madalina Icriverzi, Paula Ecaterina Florian, Anca Roseanu and Mihaela Trif

Pharmaceutics 2021, 13(8), 1108; https://doi.org/10.3390/pharmaceutics13081108 - 21 Jul 2021

Cited by 5 | Viewed by 3558

Abstract

Osteoarthritis (OA) is a degenerative joint disease. An objective of the nanomedicine and drug delivery systems field is to design suitable pharmaceutical nanocarriers with controllable properties for drug delivery and site-specific targeting, in order to achieve greater efficacy and minimal toxicity, compared to the conventional drugs. The aim of this review is to present recent data on natural bioactive compounds with anti-inflammatory properties and efficacy in the treatment of OA, their formulation in lipid nanostructured carriers, mainly liposomes, as controlled release systems and the possibility to be intra-articularly (IA) administered. The literature regarding glycosaminoglycans, proteins, polyphenols and their ability to modify the cell response and mechanisms of action in different models of inflammation are reviewed. The advantages and limits of using lipid nanoformulations as drug delivery systems in OA treatment and the suitable route of administration are also discussed. Liposomes containing glycosaminoglycans presented good biocompatibility, lack of immune system activation, targeted delivery of bioactive compounds to the site of action, protection and efficiency of the encapsulated material, and prolonged duration of action, being highly recommended as controlled delivery systems in OA therapy through IA administration. Lipid nanoformulations of polyphenols were tested both in vivo and in vitro models that mimic OA conditions after IA or other routes of administration, recommending their clinical application. Full article

(This article belongs to the Special Issue Novel Strategies for Enhancing the Therapeutic Effect of Bioactive Compounds in the Treatment of Rheumatic Diseases)

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