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Horisawa, Eijiro; Hirota, Tsuyoshi; Kawazoe, Satoko; Yamada, Jun; Yamamoto, Hiromitsu; Takeuchi, Hirofumi; Kawashima, Yasunaru

doi:10.1023/a:1015123024113

Cited by 119 publications

(23 citation statements)

References 19 publications

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“…They determined that fluorescein-loaded nanoparticles (~265 nm in diameter) were readily phagocytosed and thus caused a very minimal immunogenic response from local tissue. However, microparticles (~26 μm average diameter, but ranging from 3.1–59.9 μm) were poorly phagocytosed resulting in the formation of large granulation tissue by multinucleated giant cells (Horisawa et al 2002). Conversely, Liggins and colleagues found nearly the opposite to be true.…”

Section: Discussionmentioning

confidence: 99%

“…These strategies include encapsulation of drug in natural materials, such as chitosan, alginate, albumin protein, and elastin-like polypeptides, as well as synthetic materials such as polymers and lipids. Polymeric, drug-loaded particles, such as those constructed from materials such as poly-(lactide-co-glycolide) acid (PLGA) have been most widely studied for the delivery of small molecules to the joint space, and are now the subject of a clinical trial for the delivery of triamcinolone (Butoescu et al 2009, Horisawa et al 2002, Kumar 2013, Liang et al 2004). Similarly, liposomes have been developed to release dexamethasone following delivery to the joint space (Butoescu et al 2009, Lopez-Garcia et al 1993, Turker et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and characterization of silk fibroin microparticles for intra-articular drug delivery

Mwangi

Bowles

Tainter

et al. 2015

International Journal of Pharmaceutics

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Objective To determine the utility of silk fibroin (SF) microparticles as sustained release vehicles for intra-articular delivery. Design SF formulations were varied to generate microparticle drug carriers that were characterized in vitro for their physical properties, release kinetics for a conjugated fluorophore (Cy7), and in vivo for intra-articular retention time using live-animal, fluorescence in vivo imaging. Results SF microparticle carriers were spherical in shape and ranged from 598 nm to 21.5 μm in diameter. SF microparticles provided for sustained release of Cy7 in vitro, with only 10% of the initial load released over 7 days. Upon intra-articular injection in rat knee joints, the SF microparticles were associated with an intra-articular fluorescence decay half-life of 43.3 hours, greatly increasing the joint residence over that for an equivalent concentration of SF-Cy7 in solution form. The SF microparticles also increase the localization of dye within the joint cavity as determined by image analysis of fluorescent gradients, significantly reducing distribution of the Cy7 to neighboring tissue as compared to SF-Cy7 in free solution. Conclusion Silk microparticles act to provide for localized and sustained delivery of loaded small molecules following intra-articular injection, and may be an attractive strategy for delivering small molecule drugs for the treatment of arthritis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of silk fibroin microparticles for intra-articular drug delivery

Mwangi

Bowles

Tainter

et al. 2015

International Journal of Pharmaceutics

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“…Biodegradable microparticles composed of polyesters (for example, PGLA, PLLA), polyanhydrides, and polycaprolactones have been developed for broader clinical applications, including the encapsulation of synthetic hormones (Lupron®, Abbott), tretinoin (RetinA Micro®, OrthoNeutrogena) and risperidone (Riseperdal®, Janssen Pharma) and have shown potential for prolonging intra-articular drug residence time in preclinical studies. For betamethasone 56,58 , methotrexate 60 , diclofenac 59 , siRNA 136 and paclitaxel, 57 for example, encapsulation in microspheres composed of PLLA, PLGA, or polycaprolactones contributed to a sustained release effect in animal models of arthritis that could be observed up to 21 days after delivery in some cases. 56–60 …”

Section: Intra-articular Therapeuticsmentioning

confidence: 99%

“…For betamethasone 56,58 , methotrexate 60 , diclofenac 59 , siRNA 136 and paclitaxel, 57 for example, encapsulation in microspheres composed of PLLA, PLGA, or polycaprolactones contributed to a sustained release effect in animal models of arthritis that could be observed up to 21 days after delivery in some cases. 56–60 …”

Section: Intra-articular Therapeuticsmentioning

confidence: 99%

Progress in intra-articular therapy

2013

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Diarthrodial joints are well suited to intra-articular injection, and the local delivery of therapeutics in this fashion brings several potential advantages to the treatment of a wide range of arthropathies. Possible benefits include increased bioavailability, reduced systemic exposure, fewer adverse events, and lower total drug costs. Nevertheless, intra-articular therapy is challenging because of the rapid egress of injected materials from the joint space; this elimination is true of both small molecules, which exit via synovial capillaries, and of macromolecules, which are cleared by the lymphatic system. In general, soluble materials have an intra-articular dwell time measured only in hours. Corticosteroids and hyaluronate preparations constitute the mainstay of FDA-approved intra-articular therapeutics. Recombinant proteins, autologous blood products and analgesics have also found clinical use via intra-articular delivery. Several alternative approaches, such as local delivery of cell and gene therapy, as well as the use of microparticles, liposomes, and modified drugs, are in various stages of preclinical development.

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“…Poly(lactic- co -glycolic acid) (PLGA) has been widely employed to fabricate parenteral particulate systems, because of its long clinical use, favorable degradation characteristics, and sustained drug release profile 9,10. Horisawa et al11 revealed that PLGA-based nanoparticles (NPs) could prolong anti-inflammatory action of a corticosteroid, betamethasone sodium phosphate, by delaying the clearance rate of the active compound from the synovial cavity. Nevertheless, generally, NPs smaller than 250 nm in size quickly escape from the joint cavity, and thus longer retention times are still needed to permit less frequent IA injection 12.…”

Section: Introductionmentioning

confidence: 99%

Increased localized delivery of piroxicam by cationic nanoparticles after intra-articular injection

Kim¹,

Ho²,

Kim³

et al. 2016

DDDT

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Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA) injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA) in the synovial cavity. PRX-loaded NPs consisting of poly(lactic-co-glycolic acid), Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w) of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 μm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration–time curve (AUC0–24 h) and maximum plasma concentration (Cmax) of PRX after IA injection of the cationic NPs were <70% (P<0.05) and 60% (P<0.05), respectively, compared to those obtained from drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing with the cationic NPs was 3.2-fold (P<0.05) and 1.8-fold (P<0.05) higher than that from drug solution and neutrally charged NPs, respectively. Therefore, we recommend the IA cationic NP therapy as an effective alternative to traditional oral therapy with PRX, as it increases drug retention selectively in the joint.

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Abstract: Direct intra-articular injection of a PLGA nanosphere system with a water-soluble steroid provided a prolonged pharmacological efficacy in the joints of arthritic rabbits. The local anesthetic in the knee-joints was evaluated to be safe and without biologic damage.

Cited by 119 publications

References 19 publications

Synthesis and characterization of silk fibroin microparticles for intra-articular drug delivery

Synthesis and characterization of silk fibroin microparticles for intra-articular drug delivery

Progress in intra-articular therapy

Increased localized delivery of piroxicam by cationic nanoparticles after intra-articular injection

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