Aminocellulose-grafted-polycaprolactone coated gelatin nanoparticles alleviate inflammation in rheumatoid arthritis: A combinational therapeutic approach

Ansari, Md. Meraj; Ahmad, Anas; Kumar, Ajay; Alam, Pravej; Khan, Tajdar Husain; Jayamurugan, Govindasamy; Raza, Syed Shadab; Khan, Rehan

doi:10.1016/j.carbpol.2020.117600

Cited by 46 publications

(39 citation statements)

References 82 publications

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“…Alcian blue dye is used to stain acidic mucopolysaccharides of proteoglycans which is indicative of cartilage damage in the articular joints. 21 The negative control group (NC) had normal cartilage and bone tissues with intense alcian blue staining (shown as blue color) indicating abundance of proteoglycans. However, the positive control group (PC) exhibited obvious reduction in proteoglycan which indicated cartilage damage.…”

Section: Resultsmentioning

confidence: 99%

“…The doses were prepared under aseptic conditions to assure their sterility before IV injection and they were given every 2 days for a duration of 14 days. 20 , 21 …”

Section: Methodsmentioning

confidence: 99%

“…The doses were prepared under aseptic conditions to assure their sterility before IV injection and they were given every 2 days for a duration of 14 days. 20,21 Animal Observations Clinical signs of toxicity and mortalities were observed during the whole study. Body weights were recorded at the beginning of the experiment and once weekly afterwards to ensure safety of test samples.…”

Section: In Vivo Sub-acute Toxicity Studymentioning

confidence: 99%

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Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration

Helal¹,

Samy²,

Kamoun³

et al. 2021

IJN

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Background: Tacrolimus (TAC) is a powerful immunosuppressive agent whose therapeutic applicability is confined owing to its systemic side effects. Objective: Herein, we harnessed a natural polymer based bioconjugate composed of maltodextrin and α-tocopherol (MD-α-TOC) to encapsulate TAC as an attempt to overcome its biological limitations while enhancing its therapeutic anti-rheumatic efficacy. Methods: The designed TAC loaded maltodextrin-α-tocopherol nano-micelles (TAC@MDα-TOC) were assessed for their physical properties, safety, toxicological behavior, their ability to combat arthritis and assist bone/cartilage formation. Results: In vitro cell viability assay revealed enhanced safety profile of optimized TAC@MD-α-TOC with 1.6-to 2-fold increase in Vero cells viability compared with free TAC. Subacute toxicity study demonstrated a diminished nephro-and hepato-toxicity accompanied with optimized TAC@MD-α-TOC. TAC@MD-α-TOC also showed significantly enhanced anti-arthritic activity compared with free TAC, as reflected by improved clinical scores and decreased IL-6 and TNF-α levels in serum and synovial fluids. Unique bone formation criteria were proved with TAC@MD-α-TOC by elevated serum and synovial fluid levels of osteocalcin and osteopontin mRNA and proteins expression. Chondrogenic differentiation abilities of TAC@MD-α-TOC were proved by increased serum and synovial fluid levels of SOX9 mRNA and protein expression. Conclusion: Overall, our designed bioconjugate micelles offered an excellent approach for improved TAC safety profile with enhanced anti-arthritic activity and unique bone formation characteristics.

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Section: Resultsmentioning

confidence: 99%

“…The doses were prepared under aseptic conditions to assure their sterility before IV injection and they were given every 2 days for a duration of 14 days. 20 , 21 …”

Section: Methodsmentioning

confidence: 99%

Section: In Vivo Sub-acute Toxicity Studymentioning

confidence: 99%

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Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration

Helal¹,

Samy²,

Kamoun³

et al. 2021

IJN

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“…The product was then vacuum-dried and characterized via various methods. 24 2.2.2. Formulation of Aminocellulose-Grafted Polycaprolactone Nanoparticles.…”

Section: Methodsmentioning

confidence: 99%

“…Gel permeation chromatography (GPC) was performed as described earlier. 24 Briefly, the M w of PCL-AC was assessed by a GPC/LS instrument. GPC analysis was carried out by using a controller unit (CBM-20A) and a pumping section (LC 20AT).…”

Section: Methodsmentioning

confidence: 99%

Aminocellulose-Grafted Polymeric Nanoparticles for Selective Targeting of CHEK2-Deficient Colorectal Cancer

Ahmad¹,

Ansari²,

Verma³

et al. 2021

ACS Appl. Bio Mater.

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We report the formulation of aminocellulosegrafted polymeric nanoparticles containing LCS-1 for synthetic lethal targeting of checkpoint kinase 2 (CHEK2)-deficient HCT116 colon cancer (CRC) cells to surpass the limitations associated with the solubility of LCS-1 (a superoxide dismutase inhibitor). Aminocellulose (AC), a highly biocompatible and biodegradable hydrophilic polymer, was grafted over polycaprolactone (PCL), and a nanoprecipitation method was employed for formulating nanoparticles containing LCS-1. In this study, we exploited the synthetic lethal interaction between SOD1 and CHEK2 for the specific inhibition of CHEK2-deficient HCT116 CRC cells using LCS-1-loaded PCL-AC NPs. Furthermore, the effects of formation of protein corona on PCL-AC nanoparticles were also assessed in terms of size, cellular uptake, and cell viability. LCS-1-loaded NPs were evaluated for their size, zeta potential, and polydispersity index using a zetasizer, and their morphological characteristics were assessed by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy analyses. Cellular internalization using confocal microscopy exhibited that nanoparticles were uptaken by HCT116 cells. Also, nanoparticles were cytocompatible as they did not induce cytotoxicity in hTERT and HEK-293 cells. The LCS-1-loaded PCL-AC NPs were quite hemocompatible and were 240 times more selective in killing CHEK2-deficient cells as compared to CHEK2-proficient CRC cells. Moreover, PCL-AC NPs exhibited that the protein corona-coated nanoparticles were incubated in the human and fetal bovine sera as visualized by SDS-PAGE. A slight increment in hydrodynamic diameter was observed for corona-coated PCL-AC nanoparticles, and size increment was further confirmed by TEM. Corona-coated PCL-AC NPs also exhibited cellular uptake as demonstrated by flow cytometric analysis and did not cause cytotoxic effects on hTERT cells. The nanoformulation was developed to enhance therapeutic potential of the drug LCS-1 for enhanced lethality of colorectal cancer cells with CHEK2 deficiency.

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QbD‐Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture

Ain,

Zeeshan,

Mazhar

et al. 2023

Macromolecular Bioscience

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Biomaterials such as nanohydroxyapatite and gelatin are widely explored to improve damaged joint architecture associated with rheumatoid arthritis (RA). Besides joint damage, RA is associated with inflammation of joints and cartilage, which potentiates the need for both bone nucleation and therapeutic intervention. For such purpose, a modified nanoprecipitation method is used herein to fabricate tofacitinib (Tofa)‐loaded nanohydroxyapatite (nHA) embedded gelatin (GLT) nanoparticles (NPs) (Tofa‐nHA‐GLT NPs). The quality by design (QbD) approach is chosen to assess the key parameters that determine the efficiency of the NPs, and are further optimized via Box–Behnken design of experiment. The particle size, polydispersity, zeta potential, and encapsulation efficiency (EE) of the prepared NPs are found to be 269 nm, 0.18, −20.5 mV, and 90.7%, respectively. Furthermore, the NPs have improved stability, skin permeability, and a sustained drug release pattern at pH 6.5 (arthritic joint pH). Moreover, rhodamine‐B loaded nHA‐GLT NPs demonstrates considerably higher cellular uptake by the murine‐derived macrophages than free rhodamine‐B solution. In vitro, cell‐based experiments confirm the good cell biocompatibility with insignificant toxicity. Thus, QbD‐based approach has successfully led to the development of Tofa‐nHA‐GLT NPs with the potential to target inflamed arthritic joint.

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Aminocellulose-grafted-polycaprolactone coated gelatin nanoparticles alleviate inflammation in rheumatoid arthritis: A combinational therapeutic approach

Cited by 46 publications

References 82 publications

Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration

Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration

Aminocellulose-Grafted Polymeric Nanoparticles for Selective Targeting of CHEK2-Deficient Colorectal Cancer

QbD‐Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture

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