Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations

Abstract

liver function abnormalities. [7,8] Recently there is accumulating research interests focused on treat-to-target approaches against RA, including active interference of IL-1 pathway and other selective strategies. [9][10][11][12][13] Particularly, the treatment of blocking IL-1 is regarded as an effective targeted therapy for IL-1-directed inflammatory diseases, in contrast to attenuated performance of the non-specific antiinflammatory drugs. [13] Although the medication of IL-1 receptor antagonist (IL1ra) has been approved by the US Food and Drug Administration (FDA), it is reported that the protein IL1ra therapeutic and derivatives show short half-life from a few minutes to 1-4 h. [14][15][16] It therefore requires frequent dosage administration as high as 1-2 times per day, which greatly decreases patient compliance and results in higher expenses. [13,17] Thus, there is still largely unmet clinical need to prolong systemic circulation of the medication and increase bioavailability to realize long-acting effect and increase the drug regimen.Nanoparticle-based therapy has attracted tremendous attention in arthritis and related-biomedical communities over past few years. [18][19][20][21][22][23] Owing to its effective approach which provides protection of encapsulated payloads from degradation in the circulation, the formulation of drugs into nanoparticles has many potential advantages over conventional modalities especially in enhanced bioavailability and improved efficacy. [24,25] As a typical inflammatory disease with chronic pain syndromes, rheumatoid arthritis (RA) generally requires long-term treatment with frequent injection administration at 1-2 times per day, because common medications such as interleukin1 receptor antagonist (IL1ra) have poor bioavailability and very limited half-life residence. Here a novel strategy to fabricate nanotherapeutic formulations employing genetically engineered IL1ra protein complexes, yielding ultralong-lasting bioefficacy is developed rationally. Using rat models, it is shown that these nanotherapeutics significantly improved drug regimen to a single subcutaneous administration in a 14-day therapy, suggesting their extraordinary bioavailability and ultralong-acting pharmacokinetics. Specifically, the half-life and bioavailability of the nanoformulations are boosted to the level of 30 h and by 7 times, respectively, significantly greater than other systems. This new strategy thus holds great promise to potently improve patient compliance in RA therapy, and it can be adapted for other therapies that suffer similar drawbacks.

Biomacromolecule-based photo-thermal agents for tumor treatment

“…Biomacromolecules including cell membrane structures, proteins, nucleic acids, and polysaccharides are common materials for preparing biomimetic nanomaterials. 29,30 With their specific molecular structures, 31 innate biocompatibility, and multifunctional properties, 32 these materials are widely used in drug delivery, [33][34][35] bioimaging, 36 bioengineering, 37,38 and synthesis of hybrid PTAs. In particular, biomacromolecules like protein and double-stranded DNA can be utilized as templates to synthesize PTAs with specific 3D structures and diameters, exhibiting morphology dependent enhanced tissue penetration and cellular uptake.…”

Acupoint nanocomposite hydrogel for simulation of acupuncture and targeted delivery of triptolide against rheumatoid arthritis

“…In addition, TP is an anti-inflammatory drug that can suppress these cytokines [ 45 ]. Thus, the anti-inflammatory effect of the TP based nanocomposite hydrogel was further evaluated and the mechanism was investigated through the histological examination of proinflammatory cytokine expression [ 10 ]. As shown in Fig.…”

“…Numerous drug delivery systems like nanoparticles, emulsions, and hydrogels have been designed to transport therapeutics for arthritis treatment [ 5 – 10 ]. Nanoparticles are primarily used and often administrated by intravenous injection, but the drug concentrations in plasma are unstable, and the circulation time is short.…”

Bioengineered Protein‐based Adhesives for Biomedical Applications

“…As a typically disordered proteins, elastin-like polypeptides (ELPs) have been widely investigated over the decades. [37][38][39][40][41] It is known that ELPs consist of a repeat pentapeptide unit (VPGXG), where X can be replaced by other amino acids (Figure 2). These repeat units are derived from the alternating hydrophobic or hydrophilic domains of tropoelastin.…”