Investigating MTX-Loaded magnetic nanocomposite particles for treatment of rheumatoid arthritis

Usta, Aybala; Man, Ka P.; Strong, Nora M.; Misak, Heath Edward; Wooley, Paul H.; Asmatulu, Ramazan

doi:10.1016/j.jmmm.2019.166171

Cited by 9 publications

(3 citation statements)

References 38 publications

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“…For the establishment of the collagen-induced arthritis (CIA) rat model, adult male rats that had been habituated for at least one week in the specific pathogen-free animal room were injected subcutaneously two times with an interval of one week at the base of the tail with an emulsion (100 μL) of bovine type II collagen and complete Freund’s adjuvant. 26 , 27 At 15 days post-injection, CIA severity of hind paws was scored according to the following articular index (AI): 0, no erythema or swelling; 1, minor erythema or swelling; 2, moderate edema and signs extending to the tarsals; 3, significant edema, restricted joint utilization, and signs extending to the metatarsals; or 4, serious signs and excessive edema with joint rigidity extending to the entire hind paw. 28 , 29 The scores of each paw were summed to calculate the total AI score for each animal.…”

Section: Methodsmentioning

confidence: 99%

Long-Circulating Lipid Nanospheres Loaded with Flurbiprofen Axetil for Targeted Rheumatoid Arthritis Treatment

Chen,

Liu,

Wang

et al. 2023

IJN

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Background Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug with good analgesic and anti-inflammatory effects. However, it suffers from poor solubility, short circulation time, and off-target binding profile, which significantly limit its clinical application. Here, we loaded FA into stealth lipid microspheres modified with the arginine-glycine-aspartic acid (RGD) peptide (cRGD-FA-SLM), and examined the therapeutic potential of the resulting platform for the treatment of rheumatoid arthritis (RA). Methods cRGD-FA-SLM was prepared by high pressure homogenization, and its toxicity and uptake by macrophages were examined using cultures of RAW264.7 cells. Hemolysis and hepatotoxicity tests were performed to assess the safety of the developed platform, while its pharmacokinetics, biodistribution, and therapeutic efficacy were investigated in a collagen-induced arthritis rat model. Results cRGD-FA-SLM showed homogeneous spherical morphology and efficient encapsulation of FA. The developed platform was non-toxic to normal macrophages and was selectively internalized by lipopolysaccharide-activated macrophages in vitro, while it distributed mainly to arthritic joints and significantly prolonged FA in circulation in vivo. cRGD-FA-SLM also significantly reduced the expression of prostaglandin E2 and alleviated joint edema and bone erosion, showing prolonged analgesic effects in arthritic rats. Conclusion cRGD-FA-SLM shows good inflammation-targeting ability and prolongs drug circulation in vivo, suggesting promise as an anti-inflammatory and analgesic agent for targeted RA treatment.

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Section: Methodsmentioning

confidence: 99%

Long-Circulating Lipid Nanospheres Loaded with Flurbiprofen Axetil for Targeted Rheumatoid Arthritis Treatment

Chen,

Liu,

Wang

et al. 2023

IJN

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“…It was found that using a magnet for physically targeting the MTX to the inflamed joint helped in the remission of arthritis in the targeted joint. They also found that the drug release lasted for about 6 to 7 days and helped in slowing the progression of the disease as compared to the paws without the targeting device . Still, researchers must work toward the proper elimination of dosage form from the body to avoid any side-effects of the developed formulation.…”

Section: Albumin Implications For Rheumatoid Arthritismentioning

confidence: 99%

Role of Albumin as a Targeted Drug Carrier in the Management of Rheumatoid Arthritis: A Comprehensive Review

Garg,

Jain,

Kaul

et al. 2023

Mol. Pharmaceutics

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An endogenous transporter protein called albumin interacts with the Fc receptor to provide it with multiple substratebinding domains, cell membrane receptor activation, and an extended circulating half-life. Albumin has the remarkable ability to bind with receptors viz. secreted protein acidic and rich in cysteine (SPARC) and scavenger protein-A (SR-A) that are overexpressed during rheumatoid arthritis (RA), enabling active targeting of the disease site instead of requiring specialized substrates to be added to the nanocarrier. RA, a chronic autoimmune illness, is characterized by the presence of a severe inflammatory response. RA patients have low serum albumin concentration, which signifies the high uptake of albumin at the inflammatory sites, giving a rationale to use albumin as a drug carrier for RA therapy. Albumin has the capacity for both passive and active targeting. It is an abundantly available protein in the bloodstream showing excellent cellular compatibility, degradability in biological tissues, nonantigenicity, and safety. There are three strategies of albumin mediated drug delivery as encapsulating therapeutics in albumin nanoparticles, chemically conjugating drugs with functional proteins, and albumin itself which is used as a targeting ligand to deliver drugs specifically to cells or tissues that express albumin-binding receptors. In the current review, an attempt has been made to highlight the significant evidence of albumin as a drug delivery carrier for the safe and effective management of RA. Evidence has been provided in the form of recent research advances, clinical trials, and patents. Additionally, this review will outline the prospective for the potential utilization of albumin as a drug vehicle for RA and suggest possible future avenues to provide the perspective for subsequent studies.

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“…This approach combines the advantages of drug carrier systems and magnetic targeting. This combination has been previously applied for different drugs that can lead to toxic side effects and require localization at the site of action such as the anti-cancer drugs; doxorubicin [28] and 5-fluorouracil [5] A few studies have adopted this approach for chronic diseases such as rheumatoid arthritis and osteoarthritis [29][30][31][32] where most studies related to magnetic drug targeting are focused on the treatment of cancer.…”

Section: Introductionmentioning

confidence: 99%

Magnetic polycaprolactone microspheres: drug encapsulation and control

Gohary

Mahmoud

Nazmy

et al. 2022

International Journal of Polymeric Materials and Polymeric Biom

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Targeted drug delivery (TDD) systems have several advantages, especially with drugs having toxic side effects such as lornoxicam (LX) which shows high hepatotoxicity and nephrotoxicity, especially with long-term use. This work represents an attempt to control magnetic microspheres encapsulating LX and magnetite nanoparticles (MNPs) for potential targeted drug delivery of LX. Superparamagnetic nanoparticles were fabricated via the co-precipitation method and together with LX were encapsulated into polycaprolactone (PCL) microspheres through an oilin-water (O/W) emulsion solvent evaporation method. The effects of changing the amount of drug, MNPs, and volume of the aqueous phase were investigated by preparing several microsphere formulations. Increasing the amount of encapsulated MNPs increased the magnetization of the microspheres without affecting the morphology. Doubling the volume of the aqueous phase resulted in a higher encapsulation efficiency and drug loading; 83.9% and 10.7%, respectively, while increasing the amount of drug had a negative effect on both drug loading and encapsulation efficiency. Drug release from the microspheres was successfully achieved and showed a biphasic nature. A system of four planar coils was then used to magnetically control the movement of a cluster of capsules in a glycerin medium, as a simulation for the targeting process. The microspheres were successfully controlled to move in a U-turn path with sharp corners demonstrating their potential for TDD applications.

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Investigating MTX-Loaded magnetic nanocomposite particles for treatment of rheumatoid arthritis

Cited by 9 publications

References 38 publications

Long-Circulating Lipid Nanospheres Loaded with Flurbiprofen Axetil for Targeted Rheumatoid Arthritis Treatment

Long-Circulating Lipid Nanospheres Loaded with Flurbiprofen Axetil for Targeted Rheumatoid Arthritis Treatment

Role of Albumin as a Targeted Drug Carrier in the Management of Rheumatoid Arthritis: A Comprehensive Review

Magnetic polycaprolactone microspheres: drug encapsulation and control

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