Intra-articular Administration of Chitosan Thermosensitive In Situ Hydrogels Combined With Diclofenac Sodium–Loaded Alginate Microspheres

Qi, Xiaole; Qin, Xiaoxue; Yang, Rong; Qin, Jiayi; Li, Wenyan; Luan, Kun; Wu, Zhenghong; Song, Li

doi:10.1016/j.xphs.2015.11.019

Cited by 71 publications

(59 citation statements)

References 42 publications

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“…The in vitro slow release and ocular retention experiments demonstrated that chitosan temperature sensitive gel loaded with levofloxacin microspheres prolonged the contact duration between the microspheres and eyes, and ensured the steady and sustained release of the drug. Chitosan temperature-sensitive hydrogel must not have any adverse effects on the organizational structure of organisms when being in contact with tissues in vivo (25,26). The cell compatibility test, the cytotoxicity test and the skin irritation test in the present study have demonstrated that chitosan-based temperature-sensitive hydrogel has good biocompatibility and safety.…”

Section: Discussionmentioning

confidence: 99%

Chitosan temperature‑sensitive gel loaded with drug microspheres has excellent effectiveness, biocompatibility and safety as an ophthalmic drug delivery system

Kong

Zhang

et al. 2017

Exp Ther Med

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In the present study, a temperature-sensitive gel composed of chitosan, carboxymethyl chitosan and glycerophosphate was prepared and loaded with chitosan microspheres encapsulating levofloxacin. The bioavailability of levofloxacin and the safety of this novel opthalmic drug delivery formulation were evaluated. Levofloxacin chitosan microspheres were prepared using the ionic gelation method, and the particle size and entrapment rate were determined. The morphology of the microspheres was observed by scanning electron microscopy. The pH and zeta potential were measured. The in vitro release of levofloxacin by the chitosan temperature-sensitive gel loaded with drug microspheres was determined using spectrophotometry. The eye retention time of the chitosan temperature-sensitive gel was calculated using a fluorescein sodium test. To assess the bioavailability and safety of the chitosan temperature-sensitive gel, a cell compatibility test, a cytotoxicity test and skin irritation test were performed. The entrapment rate of levofloxacin in the chitosan microspheres was determined to be 26.5%. The levofloxacin chitosan microspheres that were formed by chitosan and sodium tripolyphosphate were identified to be suitable for use in an ophthalmic particle dispersion system based on their physical and chemical properties. The pH of the levofloxacin chitosan microsphere suspension was 5.87±0.04, the average particle diameter was 2,452±342 nm, the polydispersity index was 0.168±0.028 and the ζ potential was 28.62±1.7 mV. The chitosan temperature-sensitive gel carrying microspheres loaded with drug prevented drug burst release at the initial stage and facilitated the slow release of the drug later on. Furthermore, this delivery system markedly prolonged the contact duration of levofloxacin with the eye. The chitosan temperature-sensitive hydrogel was safe and provided a good bioavailability of the drug. The results revealed that the chitosan temperature-sensitive gel had a cytotoxicity of grade 0, and no erythematous response was observed during the entire course of the skin irritation test. The present study provided a basis for the future development of the chitosan-based temperature-sensitive hydrogel in ophthalmic drug delivery.

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Section: Discussionmentioning

confidence: 99%

Chitosan temperature‑sensitive gel loaded with drug microspheres has excellent effectiveness, biocompatibility and safety as an ophthalmic drug delivery system

Kong

Zhang

et al. 2017

Exp Ther Med

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“…In situ gelling hydrogels have shown great potential in IA drug delivery [21,23]. These hydrogels are easy to handle at room temperature, and they can be readily administered inside the joint because they are characterized by good syringeability and injectability.…”

Section: Resultsmentioning

confidence: 99%

“…The composite hydrogel made of CS/βGP and EGFR-targeted NPs (CS/βGP-NPs) provides a useful delivery platform characterized by distinctive features. CS/βGP could represent an optimal strategy to locally deliver therapeutic agents inside the joints; CS is a biocompatible polymer which can be safely used as delivery device for in situ administration [23,43,44,51]. The gel-like features of CS/βGP would be useful to tune DXM and NPs release from hydrogel formulation inside the joint avoiding the NPs leakage outside the synovial membrane; moreover, the presence of GE11 on the NPs surface could further promote the NPs uptake from EGFR-overexpressing cells improving the selective activity of the drug minimizing systemic and local side effects.…”

Section: Resultsmentioning

confidence: 99%

“…In the attempt to obtain a long-lasting release of therapeutic agents in the synovial cavity through IA administration, different drug delivery systems have been extensively investigated, such as solid lipid particles, polymeric microparticles (MPs) and nanoparticles (NPs) and their combination (NPs-in-MPs), drug–polymer conjugates, hydrogels, and in situ hydrogels as such or containing conventional MPs or NPs [4,16,17,18,19,20,21,22,23]. Overall, conventional nanoscale drug delivery system-based approaches appear very promising because IA administration appears to be simple and better penetration into cartilage tissue is achieved [4].…”

Section: Introductionmentioning

confidence: 99%

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Intra-Articular Formulation of GE11-PLGA Conjugate-Based NPs for Dexamethasone Selective Targeting—In Vitro Evaluation

Chiesa

Pisani

Colzani

et al. 2018

IJMS

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Selectively targeted nanoscale drug delivery systems have recently emerged as promising intravenously therapeutic option for most chronic joint diseases. Here, a newly synthetized dodecapeptide (GE11)-polylactide-co-glycolide (PLGA)-based conjugate was used to prepare smart nanoparticles (NPs) intended for intra-articular administration and for selectively targeting Epidermal Growth Factor Receptor (EGFR). GE11-PLGA conjugate-based NPs are specifically uptaken by EGFR-overexpressed fibroblast; such as synoviocytes; which are the primarily cellular component involved in the development of destructive joint inflammation. The selective uptake could help to tune drug effectiveness in joints and to decrease local and systemic side effects. Dexamethasone (DXM) is a glucorticoid drug commonly used in joint disease treatment for both systemic and local administration route. In the present research; DXM was efficiently loaded into GE11-PLGA conjugate-based NPs through an eco-friendly nanoprecipitation method set up for this purpose. DXM loaded GE11-PLGA conjugate-based NPs revealed satisfactory ex vivo cytocompatibility; with proper size (≤150 nm) and good dimensional stability in synovial fluid. Intra-articular formulation was developed embedding DXM loaded GE11-PLGA conjugate-based NPs into thermosetting chitosan-based hydrogel; forming a biocompatible composite hydrogel able to quickly turn from liquid state into gel state at physiological temperature; within 15 min. Moreover; the use of thermosetting chitosan-based hydrogel extends the local release of active agent; DXM.

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“…To increase drug retention time, reduction of drug clearance from joints and also increase patient compliance, different kind of controlled release delivery systems including microspheres, liposomes, NPs and hydrogels were developed. These sustained release systems for IA injection conserved effectively within the joint cavity, uptaked or kidnapped by synovial cells in the synovium [32]. Thakkar et al [33] prepared celecoxib loaded solid lipid nanoparticles (SLN) by a hot melt homogenization technique.…”

Section: Localized Drug Delivery Approachesmentioning

confidence: 99%

Recent approaches for targeted drug delivery in rheumatoid arthritis diagnosis and treatment

Chegini

Varshosaz

Taymouri

2018

Artificial Cells, Nanomedicine, and Biotechnology

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Rheumatoid arthritis (RA) is a chronic inflammatory disease with complex pathology characterized by inflammation of joints, devastation of the synovium, pannus formation, bones and cartilage destruction and often is associated with persistent arthritic pain, swelling, stiffness and work disability. In conventional RA therapy, because of short biological half-life, poor bioavailability, high and frequent dosing is required. Thereby, these anti-RA medications, which unable to selectively target affected zone, may cause severe side effects in extra-articular tissues. Today, nanotechnology has emerged as promising tool in the development of novel drug delivery systems for the treatment and diagnosis of intractable diseases such as RA. Active targeting in RA nanomedicine has also been introduced a successful way for facilitating specific uptake of therapeutic agents by the disease cells. In this review, it is attempted to describe various targeted drug delivery systems (localized and receptor-based) used for RA diagnosis and therapy. Then, we highlight recent developments related to various non-viral gene delivery systems for RA gene therapy.

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Intra-articular Administration of Chitosan Thermosensitive In Situ Hydrogels Combined With Diclofenac Sodium–Loaded Alginate Microspheres

Cited by 71 publications

References 42 publications

Chitosan temperature‑sensitive gel loaded with drug microspheres has excellent effectiveness, biocompatibility and safety as an ophthalmic drug delivery system

Chitosan temperature‑sensitive gel loaded with drug microspheres has excellent effectiveness, biocompatibility and safety as an ophthalmic drug delivery system

Intra-Articular Formulation of GE11-PLGA Conjugate-Based NPs for Dexamethasone Selective Targeting—In Vitro Evaluation

Recent approaches for targeted drug delivery in rheumatoid arthritis diagnosis and treatment

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