Journal ArticleDOI
Sustained release of IL‐1Ra from biodegradable microspheres prolongs its IL‐1‐neutralizing effects
Reads0
Chats0
TLDR
The results suggest that the present therapeutic protocol of daily bolus injections of the IL-1Ra may be replaced by a weekly injection of IL-2Ra within PLGA RG502H microspheres within rapidly degrading poly(lactic/glycolic acid) PLGARG502Hmicrospheres.Abstract:
A sustained delivery system for interleukin-1 receptor antagonist (IL-1Ra) may have great therapeutic and industrial potential due to the cytokine activity as an IL-1 inhibitor. Here, we investigated the capability of biodegradable polymeric microspheres to sustain the release and prolong the therapeutic efficacy of IL-1Ra. IL-1Ra was encapsulated within rapidly degrading poly(lactic/glycolic acid) PLGA RG502H microspheres, which showed a desirable release profile of IL-1Ra in vitro. Pharmacokinetic study in mice revealed elevated serum levels of the recombinant IL-1Ra (rIL-1Ra) for up to 8 days following subcutaneous injection of IL-1Ra microspheres. In comparison, the serum levels of rIL-1Ra following subcutaneous or intravenous bolus injection of the soluble cytokine decreased very rapidly; within 48 h no recombinant cytokine was detected in mice sera. The sustained delivery of rIL-1Ra for over two weeks was efficient in inhibiting IL-1s-stimulated induction of serum IL-6. These results suggest that the present therapeutic protocol of daily bolus injections of the IL-1Ra may be replaced by a weekly injection of IL-1Ra within PLGA RG502H microspheres.read more
Citations
More filters
Journal ArticleDOI
Anti-inflammatory polymeric coatings for implantable biomaterials and devices.
TL;DR: This minireview provides a brief background on the events of biomaterial-mediated inflammation and highlights various approaches used for modifying material surfaces to modulate inflammatory responses.
Journal ArticleDOI
Interleukin‐1 receptor antagonist: A new therapy for type 2 diabetes mellitus
TL;DR: Although, IL-1Ra has broad-spectrum anti-inflammatory activities, it also has some limitations due to its short half-life, and further studies are required to investigate its therapeutic effects against diabetes and diabetes-associated complications.
Journal ArticleDOI
Sustained Delivery of IL-1Ra from Pluronic F127-Based Thermosensitive Gel Prolongs its Therapeutic Potentials
Muhammad Sajid Hamid Akash,Muhammad Sajid Hamid Akash,Kanwal Rehman,Ni Li,Jian-Qing Gao,Hongying Sun,Shuqing Chen +6 more
TL;DR: IL-1Ra loaded PF127 gel exhibited prolonged in vitro and in vivo release, greater efficacy to induce hypoglycemia and inhibited IL-1β-stimulated production of IL-6 as compared to IL- 1Ra aq.
Journal ArticleDOI
Sustained delivery of IL-1Ra from biodegradable microspheres reduces the number of murine B16 melanoma lung metastases
TL;DR: It is shown that biodegradable microspheres represent an efficient system for sustaining IL-1Ra delivery and improving its therapeutic efficacy, and can be integrated into therapeutic protocols for treating metastatic cancers.
Journal ArticleDOI
IL-1Ra and its delivery strategies: inserting the association in perspective.
TL;DR: An overview of all approaches attempted to prolong the duration of therapeutic effects of IL-1Ra either by fusing IL- 1Ra using fusion protein technology to extend the half-life and/or development of new dosage forms using various biodegradable polymers to prolong its steady-state sustained release at the site of administration.
References
More filters
Journal ArticleDOI
Biologic basis for interleukin-1 in disease
TL;DR: This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references, which summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.
Journal ArticleDOI
Treatment of rheumatoid arthritis with recombinant human interleukin‐1 receptor antagonist
Barry Bresnihan,José María Álvaro-Gracia,Mark Cobby,Michael Doherty,Zlatko Domljan,Paul Emery,George Nuki,Karel Pavelka,Rolf Rau,Blaz Rozman,Iain Watt,Bryan D. Williams,Roger Aitchison,Dorothy McCabe,Predrag Musikic +14 more
TL;DR: IL-1Ra is the first biologic agent to demonstrate a beneficial effect on the rate of joint erosion and is confirmed both the efficacy and the safety in a large cohort of patients with active and severe RA.
Journal ArticleDOI
Controlled Delivery Systems for Proteins Based on Poly(Lactic/Glycolic Acid) Microspheres
TL;DR: Stability studies showed that the encapsulation of an enzyme inside PLGA microspheres can protect them from activity loss, and in vitro release studies revealed that different release profiles and release rates can be achieved by simply modifying factors in the preparation procedure.
Journal ArticleDOI
IL-1 is required for tumor invasiveness and angiogenesis
Elena Voronov,Dror S. Shouval,Yakov Krelin,Emanuela Cagnano,Daniel Benharroch,Yoichiro Iwakura,Charles A. Dinarello,Ron N. Apte +7 more
TL;DR: The anti-angiogenic effects of IL-1 receptor antagonist, shown here, suggest a possible therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.
Journal ArticleDOI
Renal filtration, transport, and metabolism of low-molecular-weight proteins: a review.
TL;DR: Evidence is analyzed regarding the extent, pathways, and mechanisms of the renal accumulation, filtration, absorption, and metabolism of small proteins, a heterogenous group of substances which constitute a small but biologically important fraction of total circulating proteins.