Pharmaceutics

Research

14 pages, 3645 KiB

Open AccessArticle

Hyaluronic Acid Hampers the Inflammatory Response Elicited by Extracellular Vesicles from Activated Monocytes in Human Chondrocytes

by Vittoria Carrabs, Maria Isabel Guillén, María Luisa Ferrándiz, María José Alcaraz, Fabio Ferrini, Rachele Agostini, Michele Guescini, Carmela Fimognari, Italo Capparucci, Elena Barbieri and Piero Sestili

Pharmaceutics 2024, 16(11), 1386; https://doi.org/10.3390/pharmaceutics16111386 - 28 Oct 2024

Viewed by 988

Abstract

Background/Objectives: Osteoarthritis (OA) is the most common joint disease in the adult population. OA is the result of multiple mechanisms leading to inflammation and the degradation of the cartilage. A complex series of etiological actors have been identified so far, including extracellular vesicles [...] Read more.

Background/Objectives: Osteoarthritis (OA) is the most common joint disease in the adult population. OA is the result of multiple mechanisms leading to inflammation and the degradation of the cartilage. A complex series of etiological actors have been identified so far, including extracellular vesicles (EVs). The EV content of the synovial fluid (SF) can release inflammatory mediators that enhance OA progression. An intra-articular viscosupplementation of high-MW hyaluronic acid (HyA) constitutes the first-line conservative treatment for OA. Although attractive for the potential pharmacological implications, the possibility that HyA may interact with EVs in the context of OA has not yet been specifically investigated; therefore, the present study aimed to fill this gap. Methods: We studied the effect of a HyA preparation (a blend of crosslinked and linear polymers, CLHyA) on the relevant inflammatory markers in chondrocytes (HC cells or primary chondrocytes isolated from patients with advanced OA) exposed to the EVs collected from IL-1β-stimulated THP-1 human monocytes (EVs+). Results: EVs+ caused specific inflammatory responses in chondrocytes that could be prevented by coincubation with CLHyA. This anti-inflammatory activity is likely dependent on the direct binding of CLHyA to CD44 receptors highly expressed in EVs+ and on the subsequent hindrance to EVs+ diffusion and docking to target cells. Conclusions: On the whole, the tight interactions identified herein between HMW HyA and EVs+ represent a novel, pharmacologically exploitable mechanism potentially relevant in the context of OA treatment. Full article

(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)

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10 pages, 1758 KiB

Open AccessArticle

Strengthening the Key Features of Volumizing Fillers: Projection Capacity and Long-Term Persistence

by Killian Flégeau, Jing Jing, Camille Vantou, Romain Brusini, François Bourdon and Jimmy Faivre

Pharmaceutics 2023, 15(11), 2585; https://doi.org/10.3390/pharmaceutics15112585 - 4 Nov 2023

Cited by 3 | Viewed by 2354

Abstract

Volumizing fillers aim to create or restore facial volume in fat layers. To provide strong tissue lifting and long-term persistence, gels are generally designed with stiff properties, characterized by a high storage modulus (G′). However, clinical evidence shows a discrepancy between high G′ [...] Read more.

Volumizing fillers aim to create or restore facial volume in fat layers. To provide strong tissue lifting and long-term persistence, gels are generally designed with stiff properties, characterized by a high storage modulus (G′). However, clinical evidence shows a discrepancy between high G′ and good lifting capacities, especially after skin tension has been exerted on the gel. To better explore the in vivo behavior of a gel, we first evaluated the elastic moduli of five commercial volumizers (RHA₄, JUV_VOL, RES_VOL, RES_LYFT, and BEL_VOL) in dynamic compression mode, E′. We further developed a Projection Index score based on the rheological assessment of creep in compression to mimic skin tension-induced stress relaxation (flattening). Finally, the ability of a gel to resist enzymatic degradation was analyzed with a multidose approach. Despite similar clinical indications, volumizers exhibited distinct behaviors. RHA₄ and BEL_VOL showed the highest E′ values (resistance to strain), RHA₄, JUV_VOL, and RES_VOL exhibited the greatest projection capacities, while JUV_VOL and RHA₄ offered the largest persistence to enzymatic degradation. In this article, we introduce the use of the Projection Index to efficiently assess the ability of a gel to lift tissues, thus increasing preclinical models’ efficiency and reducing the need for animal studies. Full article

(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)

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12 pages, 10447 KiB

Open AccessArticle

Enhancing Dental Applications: A Novel Approach for Incorporating Bioactive Substances into Textile Threads

by Marek Pokorný, Jolana Kubíčková, Jan Klemeš, Tomáš Medek, Adam Brýdl, Martina Pachovská, Tereza Hanová, Josef Chmelař and Vladimír Velebný

Pharmaceutics 2023, 15(10), 2487; https://doi.org/10.3390/pharmaceutics15102487 - 18 Oct 2023

Viewed by 1325

Abstract

In the realm of surgical and dental applications, hyaluronic acid (HA) braided threads show significant therapeutic potential due to their incorporation of pharmaceutical active ingredients. This study primarily focuses on resolving the crucial challenge of devising a deposition method that can ensure both [...] Read more.

In the realm of surgical and dental applications, hyaluronic acid (HA) braided threads show significant therapeutic potential due to their incorporation of pharmaceutical active ingredients. This study primarily focuses on resolving the crucial challenge of devising a deposition method that can ensure both precision and uniformity in the content of the active ingredient Octenidine dihydrochloride (OCT) within each segment of the threads. Our objective in this study was to develop a continuous deposition method for OCT onto a braided thread composed of 24 hyaluronic acid-based fibers, aiming for a specific OCT content of 0.125 µg/mm, while maintaining a maximum allowable deviation of ±15% in OCT content. The motivation behind designing this novel method stemmed from the necessity of employing a volatile solvent for the active agent. Conventional wetting methods proved unsuitable due to fluctuations in the solution’s concentration during deposition, and alternative methods known to us demanded intricate technical implementations. The newly introduced method offers distinct advantages, including its online processing speed, scalability potential, and cost-efficiency of the active agent solution. Additionally, it minimizes the impact on the natural polymer thread, preserving energy by obviating the need for complete thread saturation. Our research and precise apparatus development resulted in achieving the desired thread properties, with an OCT content of (1.51 ± 0.09) µg per 12 mm thread piece. These findings not only validate the suitability of this innovative method for depositing active agents but also extend its potential applicability beyond dental care. Full article

(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)

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12 pages, 2091 KiB

Open AccessArticle

Clinical Efficacy of Hyaluronic Acid with Iodine in Hard-to-Heal Wounds

by Jana Pecová, Vladimíra Rohlíková, Markéta Šmoldasová and Jan Marek

Pharmaceutics 2023, 15(9), 2268; https://doi.org/10.3390/pharmaceutics15092268 - 1 Sep 2023

Cited by 3 | Viewed by 2289

Abstract

Hard-to-heal wounds do not heal spontaneously and need long-term care provided by specialists. That burdens the patients as well as the healthcare systems. Such wounds arise from several pathologies, which result in venous leg ulcers (VLU), diabetic foot ulcers (DFU), pressure ulcers (PU), [...] Read more.

Hard-to-heal wounds do not heal spontaneously and need long-term care provided by specialists. That burdens the patients as well as the healthcare systems. Such wounds arise from several pathologies, which result in venous leg ulcers (VLU), diabetic foot ulcers (DFU), pressure ulcers (PU), or ulcers originating from post-surgical wounds (pSW). Given the complex nature of hard-to-heal wounds, novel treatments are sought to enable wound healing. We tested the clinical efficacy and applicability of fluid comprising hyaluronic acid and iodine complex (HA-I) in the treatment of hard-to-heal wounds. Patients (n = 56) with VLU, DFU, PU, or pSW hospitalised in multiple wound-care centres in the Czech Republic were treated with HA-I. Wound size, classically visible signs of infection, exudation, pain, and wound bed appearance were monitored for 12 weeks. The highest healing rate was in DFU (71.4%), followed by pSW (62.5%), VLU (55.6%), and PU (44.4%). Classical visible signs of infection were resolved within 8 weeks in all types of wounds. Wound bed appearance improved most noticeably in pSW and then in VLU. Exudation was lowered most significantly in DFU and pSW. The highest decrease in pain was in pSW and DFU. The treatment with HA-I successfully led to either complete closure or significant improvement in the wound’s healing. Therefore, the complex of hyaluronic acid and iodine is suitable for the treatment of hard-to-heal wounds of various aetiologies. Full article

(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)

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18 pages, 4673 KiB

Open AccessArticle

Injectable Hyaluronan-Based Thermoresponsive Hydrogels for Dermatological Applications

by Si Gou, Alexandre Porcello, Eric Allémann, Denis Salomon, Patrick Micheels, Olivier Jordan and Yogeshvar N. Kalia

Pharmaceutics 2023, 15(6), 1708; https://doi.org/10.3390/pharmaceutics15061708 - 11 Jun 2023

Cited by 11 | Viewed by 2714

Abstract

Most marketed HA-based dermal fillers use chemical cross-linking to improve mechanical properties and extend their lifetime in vivo; however, stiffer products with higher elasticity require an increased extrusion force for injection in clinical practice. To balance longevity and injectability, we propose a thermosensitive [...] Read more.

Most marketed HA-based dermal fillers use chemical cross-linking to improve mechanical properties and extend their lifetime in vivo; however, stiffer products with higher elasticity require an increased extrusion force for injection in clinical practice. To balance longevity and injectability, we propose a thermosensitive dermal filler, injectable as a low viscosity fluid that undergoes gelation in situ upon injection. To this end, HA was conjugated via a linker to poly(N-isopropylacrylamide) (pNIPAM), a thermosensitive polymer using “green chemistry”, with water as the solvent. HA-L-pNIPAM hydrogels showed a comparatively low viscosity (G′ was 105.1 and 233 for Candidate1 and Belotero Volume^®, respectively) at room temperature and spontaneously formed a stiffer gel with submicron structure at body temperature. Hydrogel formulations exhibited superior resistance against enzymatic and oxidative degradation and could be administered using a comparatively lower injection force (49 N and >100 N for Candidate 1 and Belotero Volume^®, respectively) with a 32G needle. Formulations were biocompatible (viability of L929 mouse fibroblasts was >100% and ~85% for HA-L-pNIPAM hydrogel aqueous extract and their degradation product, respectively), and offered an extended residence time (up to 72 h) at the injection site. This property could potentially be exploited to develop sustained release drug delivery systems for the management of dermatologic and systemic disorders. Full article

(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)

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30 pages, 2981 KiB

Open AccessArticle

Thermo-Responsive Hyaluronan-Based Hydrogels Combined with Allogeneic Cytotherapeutics for the Treatment of Osteoarthritis

by Alexandre Porcello, Paula Gonzalez-Fernandez, Annick Jeannerat, Cédric Peneveyre, Philippe Abdel-Sayed, Corinne Scaletta, Wassim Raffoul, Nathalie Hirt-Burri, Lee Ann Applegate, Eric Allémann, Alexis Laurent and Olivier Jordan

Pharmaceutics 2023, 15(5), 1528; https://doi.org/10.3390/pharmaceutics15051528 - 18 May 2023

Cited by 7 | Viewed by 2227

Abstract

Thermo-responsive hyaluronan-based hydrogels and FE002 human primary chondroprogenitor cell sources have both been previously proposed as modern therapeutic options for the management of osteoarthritis (OA). For the translational development of a potential orthopedic combination product based on both technologies, respective technical aspects required [...] Read more.

Thermo-responsive hyaluronan-based hydrogels and FE002 human primary chondroprogenitor cell sources have both been previously proposed as modern therapeutic options for the management of osteoarthritis (OA). For the translational development of a potential orthopedic combination product based on both technologies, respective technical aspects required further optimization phases (e.g., hydrogel synthesis upscaling and sterilization, FE002 cytotherapeutic material stabilization). The first aim of the present study was to perform multi-step in vitro characterization of several combination product formulas throughout the established and the optimized manufacturing workflows, with a strong focus set on critical functional parameters. The second aim of the present study was to assess the applicability and the efficacy of the considered combination product prototypes in a rodent model of knee OA. Specific characterization results (i.e., spectral analysis, rheology, tribology, injectability, degradation assays, in vitro biocompatibility) of hyaluronan-based hydrogels modified with sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly(N-isopropylacrylamide) (HA-L-PNIPAM) containing lyophilized FE002 human chondroprogenitors confirmed the suitability of the considered combination product components. Specifically, significantly enhanced resistance toward oxidative and enzymatic degradation was shown in vitro for the studied injectable combination product prototypes. Furthermore, extensive multi-parametric (i.e., tomography, histology, scoring) in vivo investigation of the effects of FE002 cell-laden HA-L-PNIPAM hydrogels in a rodent model revealed no general or local iatrogenic adverse effects, whereas it did reveal some beneficial trends against the development of knee OA. Overall, the present study addressed key aspects of the preclinical development process for novel biologically-based orthopedic combination products and shall serve as a robust methodological basis for further translational investigation and clinical work. Full article

(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)

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Review

Jump to: Research, Other

18 pages, 603 KiB

Open AccessReview

Hyaluronic Acid in Rheumatology

by Haiko Sprott and Christian Fleck

Pharmaceutics 2023, 15(9), 2247; https://doi.org/10.3390/pharmaceutics15092247 - 30 Aug 2023

Cited by 24 | Viewed by 4391

Abstract

Hyaluronic acid (HA), also known as hyaluronan, is an anionic glycosaminoglycan widely distributed throughout various tissues of the human body. It stands out from other glycosaminoglycans as it lacks sulfation and can attain considerable size: the average human synovial HA molecule weighs about [...] Read more.

Hyaluronic acid (HA), also known as hyaluronan, is an anionic glycosaminoglycan widely distributed throughout various tissues of the human body. It stands out from other glycosaminoglycans as it lacks sulfation and can attain considerable size: the average human synovial HA molecule weighs about 7 million Dalton (Da), equivalent to roughly 20,000 disaccharide monomers; although some sources report a lower range of 3–4 million Da. In recent years, HA has garnered significant attention in the field of rheumatology due to its involvement in joint lubrication, cartilage maintenance, and modulation of inflammatory and/or immune responses. This review aims to provide a comprehensive overview of HA’s involvement in rheumatology, covering its physiology, pharmacology, therapeutic applications, and potential future directions for enhancing patient outcomes. Nevertheless, the use of HA therapy in rheumatology remains controversial with conflicting evidence regarding its efficacy and safety. In conclusion, HA represents a promising therapeutic option to improve joint function and alleviate inflammation and pain. Full article

(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)

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Other

Jump to: Research, Review

11 pages, 1228 KiB

Open AccessSystematic Review

The Effect of Adjunctive Use of Hyaluronic Acid on Prevalence of Porphyromonas gingivalis in Subgingival Biofilm in Patients with Chronic Periodontitis: A Systematic Review

by Fahad A. Alshehri and Meshal S. Alharbi

Pharmaceutics 2023, 15(7), 1883; https://doi.org/10.3390/pharmaceutics15071883 - 4 Jul 2023

Cited by 7 | Viewed by 1797

Abstract

Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic bacterium that plays an important role in the development and progression of periodontitis. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has previously demonstrated antibacterial potential in vitro against multiple bacterial species, [...] Read more.

Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic bacterium that plays an important role in the development and progression of periodontitis. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has previously demonstrated antibacterial potential in vitro against multiple bacterial species, including P. gingivalis. The purpose of this systematic review is to evaluate the effectiveness of HA as an adjunctive topical antibacterial agent to non-surgical mechanical therapy of periodontitis in reducing the prevalence of P. gingivalis in subgingival biofilms. Five clinical studies were identified that satisfied the eligibility criteria. Only three trials were suitable for the meta-analysis as they provided data at three and six months. Data on the prevalence of P. gingivalis in each study were collected. The odds ratio (OR) for measuring the effect size with a 95% confidence interval (CI) was applied to the available data. The results did not favor the use of HA during non-surgical mechanical therapy to reduce the prevalence of P. gingivalis in subgingival biofilm (odd ratio = 0.95 and 1.11 at three and six months, consecutively). Within their limitations, the current data do not indicate an advantage for using HA during mechanical periodontal therapy to reduce the prevalence of P. gingivalis. Full article

(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)

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