Intra‐articular depot formulation principles: Role in the management of postoperative pain and arthritic disorders

Larsen, Claus; Østergaard, Jesper; Larsen, Susan Weng; Jensen, Henrik; Jacobsen, Stine; Lindegaard, Claus; Andersen, Pia Haubro

doi:10.1002/jps.21346

Cited by 245 publications

(209 citation statements)

References 305 publications

(353 reference statements)

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“…To date the pharmaceutical industry has failed to provide effective and safe DMOADs for clinical use [13]. The main reasons are that despite their specific targeted action DMOADs still can cause side effects when administered systemically [14][15][16], or when injected intra-articular have a short residence time within the joint [17,18]. It remains unclear how long particular drugs have to remain in the joint for an effective pain relief and/or disease modification after an intra-articular injection.…”

Section: Clinical Needsmentioning

confidence: 99%

“…It remains unclear how long particular drugs have to remain in the joint for an effective pain relief and/or disease modification after an intra-articular injection. Without a drug delivery system (DDS), synovial disappearance time of a drug in the joint is often short and except for cross-linked HA usually drugs do not reside much longer than 24 hours [18]. Direct intra-articular drug delivery allows for an effective concentration where it is needed with a minimum of drugs.…”

Section: Clinical Needsmentioning

confidence: 99%

“…Elron-Gross et al reported a reduction of inflammation in a monosodium iodoacetate (MIA) induced OA rat knee after a liposomal dexamethasone and diclofenac combination injection as compared to control assessed by MRI, in 2009 [32,92], and Dong et al found a combination of Cxb incorporated liposomes and HA to be more effective in pain control and cartilage protection than a single Cxb injection, Cxb liposome, and HA treatment alone [93]. Although liposomes are well established, and are effective and biocompatible, IA residence time is relatively short compared to other DDSs [18].…”

Section: Liposomesmentioning

confidence: 99%

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Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

et al. 2014

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Osteoarthritis (OA) is a big burden of disease worldwide and one of the most common causes of disability in the adult population. Currently applied therapies consist of physical therapy, oral medication, intra-articular injections, and surgical interventions, with the main goal being to reduce pain and improve function and quality of life. Intra-articular (IA) administration of drugs has potential benefits in OA treatment because it minimizes systemic bioavailability and side effects associated with oral administration of drugs without compromising the therapeutic effect in the joint. However, IA drug residence time is short and there is a clinical need for a vehicle that is able to provide a sustained release long enough for IA therapy to fulfill its promise. This review summarizes the use of different polymeric systems and the incorporated drugs for IA drug delivery in the osteoarthritic joint with a primary focus on clinical needs and opportunities.

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Section: Clinical Needsmentioning

confidence: 99%

Section: Clinical Needsmentioning

confidence: 99%

Section: Liposomesmentioning

confidence: 99%

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Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

et al. 2014

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“…According to these phases, two types of drugs, which are commonly prescribed are antiinflammatory agents non-steroidal antiinflammatory drugs (NSAIDs) and glucocorticoids and disease modifying antirheumatic drugs (DMARDs). Using biological agents, immune suppressants and gene therapy are some newer strategies for the treatment of RA [3] .…”

mentioning

confidence: 99%

Biodegradable Gelatin Microspheres as Controlled Release Intraarticular Delivery System: The Effect of Formulation Variables

Farhangi¹

2017

ijps

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Farhangi, et al.: Gelatin Microspheres for Intraarticular DeliveryIntraarticular administration of microspheres containing non-steroidal antiinflammatory drugs is beneficial in the treatment of rheumatoid arthritis. Microspheres could localize drug at the site of administration and control its release, resulting in improved therapeutic effects and decreased side effects. Therefore, the objective of the present study was to prepare controlled release meloxicam-loaded gelatin microspheres and evaluate the effect of various variables on their properties. Meloxicam-loaded microspheres were prepared by emulsion-congealing-chemical cross-linking method. Different amounts of polymer, emulsifier and crosslinking agent, as formulation variables, were evaluated. Microspheres were characterized in terms of yield value, encapsulation efficiency and the drug release pattern. The particle size, surface morphology and thermal behaviour of microspheres were also investigated. According to the results, using glutaraldehyde as a cross-linking agent resulted in spherical microspheres with the yield value of 63-96% and encapsulation efficiency of 23-63%. The optimum formulation with the mean particle size of about 57 μm, showed slow drug release profile (64%) throughout 48 h. An appropriate polymer:cross-linker ratio must be used to obtain suitable particles with acceptable controlled released behaviour. In summary the results of the present study supported the preparation of sustained release meloxicam-loaded microspheres using emulsion-congealing method along with the potential application of glutaraldehyde in improving the physical properties of prepared particles as well as the release profile of this low water soluble drug.

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“…Nevertheless, the delivery of IA-injected small molecules and macromolecules into chondrocytes has been limited by the fast clearance out of the synovial cavity and poor diffusion through the tight cartilage matrix. 4 This problem has been recently tackled through the use of a new class of drugs based upon multifunctional nanoparticles designed to selectively and safely deliver therapeutic agents to a diseased site. 5 In an OA prevention study published in a recent issue of Gene Therapy, Pi et al 6 described the use of polyetheleneimine (PEI) to fabricate chondrocyte-targeting nanoparticles.…”

mentioning

confidence: 99%

Tackling chondrocyte hypertrophy with multifunctional nanoparticles

et al. 2016

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Osteoarthritis (OA) is the most common form of arthritis and leads to irreversible changes in all articular tissues and associated skeletal muscle.1,2 OA is a collection of different phenotypic subtypes involving different relative contributions of the stressors and pathogenic pathways that trigger and drive, respectively, disease development ( Figure 1). Recent investigations have shown that OA is driven by interplay between local joint inflammation (synovitis) and chondrocyte impaired bioenergy and protein homeostasis (see Liu-Bryan and Terkeltaub 2 for an excellent review). Another important pathway being studied in the OA field is that chondrocytes acquire a phenotype similar to terminal differentiating chondrocytes found at the growth plate and express markers of hypertrophic chondrocytes including type X collagen, matrix metalloproteinase-13 (MMP13) and vascular endothelial growth factor (VEGF).3 These findings suggest that the loss of phenotypic stability of chondrocytes in OA reflects an early futile process to repair stressed cartilage that ultimately leads to pathologic cartilage calcification.Chondrocyte hypertrophy is regulated by the activation of a constellation of transcription factors and other signalling molecules. Studies with knockout and transgenic mice have shown that deletion of many of these regulators results in resistance to OA development, thus suggesting that blocking chondrocyte hypertrophy by targeting these regulators in chondrocytes would be a valid therapeutic approach for OA. The direct exposure of the cartilage to the joint cavity makes chondrocytes amenable to targeting via intra-articular (IA) injection. This route offers the advantages of high joint bioavailability while reducing the risk of off-target effects. Nevertheless, the delivery of IA-injected small molecules and macromolecules into chondrocytes has been limited by the fast clearance out of the synovial cavity and poor diffusion through the tight cartilage matrix. 4 This problem has been recently tackled through the use of a new class of drugs based upon multifunctional nanoparticles designed to selectively and safely deliver therapeutic agents to a diseased site. 5 In an OA prevention study published in a recent issue of Gene Therapy, Pi et al.6 described the use of polyetheleneimine (PEI) to fabricate chondrocyte-targeting nanoparticles. PEI was first conjugated to a chondrocyte-affinity peptide (CAP; DWRVIIPPRPSAC) and, next, used to condense an siRNA against hypoxia-inducible factor-2α (Hif-2α) in nanoparticles. The nanoparticles were injected weekly into the knees of 8-week-old male Chinese Kun Ming mice at the onset of OA, that is, 3 days after surgical destabilization of the knee joints by dissecting the anterior cruciate ligament (ACL), medial collateral ligament (MCL) and anterior horn of the medial meniscus. After seven weeks, mice treated with CAP-coated nanoparticles showed a significant reduction in cartilage breakdown and synovitis compared with sham-treated mice or OA mice treated with nanoparticles co...

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Intra‐articular depot formulation principles: Role in the management of postoperative pain and arthritic disorders

Cited by 245 publications

References 305 publications

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

Biodegradable Gelatin Microspheres as Controlled Release Intraarticular Delivery System: The Effect of Formulation Variables

Tackling chondrocyte hypertrophy with multifunctional nanoparticles

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