scholarly journals Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus

2018 ◽  
Vol 19 (8) ◽  
pp. 2310 ◽  
Author(s):  
Enrica Chiesa ◽  
Rossella Dorati ◽  
Bice Conti ◽  
Tiziana Modena ◽  
Emanuela Cova ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Chitosan Nanoparticles ◽  
Mesenchymal Cells ◽  
Bronchiolitis Obliterans Syndrome ◽  
Process Conditions ◽  
Uptake Mechanism ◽  
Organ Rejection ◽  
Matrix Deposition

Bronchiolitis obliterans syndrome (BOS), caused by lung allograft-derived mesenchymal cells’ abnormal proliferation and extracellular matrix deposition, is the main cause of lung allograft rejection. In this study, a mild one-step ionotropic gelation method was set up to nanoencapsulate the everolimus, a key molecule in allograft organ rejection prevention, into hyaluronic acid-decorated chitosan-based nanoparticles. Rationale was the selective delivery of everolimus into lung allograft-derived mesenchymal cells; these cells are characterized by the CD44-overexpressing feature, and hyaluronic acid has proven to be a natural selective CD44-targeting moiety. The optimal process conditions were established by a design of experiment approach (full factorial design) aiming at the control of the nanoparticle size (≤200 nm), minimizing the size polydispersity (PDI 0.171 ± 0.04), and at the negative ζ potential maximization (−30.9 mV). The everolimus was successfully loaded into hyaluronic acid-decorated chitosan-based nanoparticles (95.94 ± 13.68 μg/100 mg nanoparticles) and in vitro released in 24 h. The hyaluronic acid decoration on the nanoparticles provided targetability to CD44-overexpressing mesenchymal cells isolated from bronchoalveolar lavage of BOS-affected patients. The mesenchymal cells’ growth tests along with the nanoparticles uptake studies, at 37 °C and 4 °C, respectively, demonstrated a clear improvement of everolimus inhibitory activity when it is encapsulated in hyaluronic acid-decorated chitosan-based nanoparticles, ascribable to their active uptake mechanism.

Targeted delivery of a short antimicrobial peptide against CD44-overexpressing tumor cells using hyaluronic acid-coated chitosan nanoparticles: An in vitro study

2020 ◽  
Vol 22 (5) ◽  
Author(s):  
Vahid Taghipour-Sabzevar ◽  
Tahere Sharifi ◽  
Shadab Bagheri-Khoulenjani ◽  
Vahabodin Goodarzi ◽  
Hamid Kooshki ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Antimicrobial Peptide ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Chitosan Nanoparticles ◽  
In Vitro Study ◽  
Vitro Study

scholarly journals Hyaluronic Acid–Decorated Liposomes as Innovative Targeted Delivery System for Lung Fibrotic Cells

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3291 ◽  
Author(s):  
Laura Pandolfi ◽  
Vanessa Frangipane ◽  
Claudia Bocca ◽  
Alessandro Marengo ◽  
Erika Tarro Genta ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Immune Modulation ◽  
Bronchiolitis Obliterans Syndrome ◽  
Molecular Weights ◽  
Matrix Deposition ◽  
Targeting Efficiency ◽  
Healthy Donors ◽  
Extracellular Matrix Deposition ◽  
Collagen Tissue

Collagen Tissue Disease–associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS) represent severe lung fibrogenic disorders, characterized by fibro-proliferation with uncontrolled extracellular matrix deposition. Hyaluronic acid (HA) plays a key role in fibrosis with its specific receptor, CD44, overexpressed by CTD-ILD and BOS cells. The aim is to use HA-liposomes to develop an inhalatory treatment for these diseases. Liposomes with HA of two molecular weights were prepared and characterized. Targeting efficiency was assessed toward CTD-ILD and BOS cells by flow cytometry and confocal microscopy and immune modulation by RT-PCR and ELISA techniques. HA-liposomes were internalized by CTD-ILD and BOS cells expressing CD44, and this effect increased with higher HA MW. In THP-1 cells, HA-liposomes decreased pro-inflammatory cytokines IL-1β, IL-12, and anti-fibrotic VEGF transcripts but increased TGF-β mRNA. However, upon analyzing TGF-β release from healthy donors-derived monocytes, we found liposomes did not alter the release of active pro-fibrotic cytokine. All liposomes induced mild activation of neutrophils regardless of the presence of HA. HA liposomes could be also applied for lung fibrotic diseases, being endowed with low pro-inflammatory activity, and results confirmed that higher MW HA are associated to an increased targeting efficiency for CD44 expressing LFs-derived from BOS and CTD-ILD patients.

scholarly journals Photocuring Hyaluronic Acid/Silk Fibroin Hydrogel Containing Curcumin Loaded CHITOSAN Nanoparticles for the Treatment of MG-63 Cells and ME3T3-E1 Cells

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2302
Author(s):  
Qingwen Yu ◽  
Zhiyuan Meng ◽  
Yichao Liu ◽  
Zehao Li ◽  
Xing Sun ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Bone Regeneration ◽  
Water Uptake ◽  
Silk Fibroin ◽  
Bone Repair ◽  
Ph Value ◽  
Chitosan Nanoparticles ◽  
Vitro Assay ◽  
Long Term Treatment

After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. In this study, the curcumin (Cur) loaded chitosan (CS) nanoparticles (CCNP) encapsulated silk fibroin (SF)/hyaluronic acid esterified by methacrylate (HAMA) (CCNPs-SF/HAMA) hydrogel for the osteosarcoma therapy and bone regeneration was developed by photocuring and ethanol treatment. The micro or nanofibers networks were observed in the CCNPs-SF/HAMA hydrogel. The FTIR results demonstrated that alcohol vapor treatment caused an increase in β-sheets of SF, resulting in the high compression stress and Young’s modulus of CCNPs-SF/HAMA hydrogel. According to the water uptake analysis, SF caused a slight decrease in water uptake of CCNPs-SF/HAMA hydrogel while CCNPs could enhance the water uptake of it. The swelling kinetic results showed that both the CCNPs and the SF increased the swelling ratio of CCNPs-SF/HAMA hydrogel. The accumulative release profile of CCNPs-SF/HAMA hydrogel showed that the release of Cur from CCNPs-SF/HAMA hydrogel was accelerated when pH value was decreased from 7.4 to 5.5. Besides, compared with CCNPs, the CCNPs-SF/HAMA hydrogel had a more sustainable drug release, which was beneficial for the long-term treatment of osteosarcoma. In vitro assay results indicated that CCNPs-SF/HAMA hydrogel with equivalent Cur concentration of 150 μg/mL possessed both the effect of anti-cancer and promoting the proliferation of osteoblasts. These results suggest that CCNPs-SF/HAMA hydrogel with superior physical properties and the bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.

Intra-articular Administrated Hydrogels of Hyaluronic Acid Hybridized with Triptolide/Gold Nanoparticles for Targeted Delivery to Rheumatoid Arthritis Combined with Photothermal-chemo Therapy

2021 ◽  
Author(s):  
Chenxi Li ◽  
Rui Liu ◽  
Yurong Song ◽  
Dongjie Zhu ◽  
Liuchunyang Yu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Invasion And Migration ◽  
Nir Light ◽  
Hybrid Hydrogels ◽  
And Migration

Abstract Triptolide (TP) as a disease-modifying anti-rheumatic drug (DMARD) is effective on the treatment of rheumatoid arthritis (RA). To alleviate the toxicity and elevate therapeutic specificity, hyaluronic acid (HA) hydrogels load RGD-attached gold nanoshell containing TP are synthesized, which can be used for targeted photothermal-chemo therapy, and imaging of RA in vivo. The hydrogels system composed of thiol and tyramine modified HA conjugates has been applied artificial tissue models of cartilage for studying drug delivery and release properties. After the degradation of HA chains, heat together with drugs can be delivered to the inflammatory joints simultaneously due to the near-infrared resonance (NIR) irradiation of Au nanoshell. RA is a chronic inflamed disease, which is characterized by synovial inflammation of multiple joints, and can be penetrated with NIR light. These intra-articular administrated hybrid hydrogels combined with NIR irradiation can improve clinical arthritic conditions and inflamed joints in collagen-induced arthritis (CIA) mice, which just need a smaller dosage of TP with non-toxicity. Additionally, the TP-Au/HA hybrid hydrogels treatment reduced the invasion and migration of RA fibroblast-like synoviocytes (RA-FLSs) in vitro significantly, through reducing the phosphorylation of mTOR and p70S6K, its substrates, and confirmed that the mTOR pathway was inhibited.

Fibronectin gene expression during limb cartilage differentiation

Development ◽  
1989 ◽  
Vol 106 (3) ◽  
pp. 449-455 ◽  
Author(s):  
W.M. Kulyk ◽  
W.B. Upholt ◽  
R.A. Kosher
Keyword(s):  
Relative Rate ◽  
Mesenchymal Cells ◽  
Cartilage Matrix ◽  
Condensation Process ◽  
Mrna Levels ◽  
Matrix Deposition ◽  
Cartilage Differentiation ◽  
Low Levels

A critical event in limb cartilage differentiation is a transient cellular condensation process in which prechondrogenic mesenchymal cells become closely juxtaposed and interact with one another prior to initiating cartilage matrix deposition. Fibronectin (FN) has been suggested to be involved in regulating the onset of condensation and chondrogenesis by actively promoting prechondrogenic aggregate formation during the process. We have performed a systematic quantitative study of the expression of the FN gene during the progression of chondrogenesis in vitro and in vivo. In high-density micromass cultures of limb mesenchymal cells, FN mRNA levels increase about 5-fold coincident with the crucial condensation process, and remain relatively high during the initial deposition of cartilage matrix by the cells. Thereafter, FN mRNA levels progressively decline to relatively low levels as the cultures form a virtually uniform mass of cartilage. The changes in FN mRNA levels in vitro are paralleled closely by changes in the relative rate of FN synthesis as determined by pulse-labeling and immunoprecipitation analysis. The relative rate of FN synthesis increases 4- to 5-fold at condensation and the onset of chondrogenesis, after which it progressively declines to low levels as cartilage matrix accumulates. High levels of FN gene expression also occur at the onset of chondrogenesis in vivo. In the proximal central core regions of the limb bud in which condensation and cartilage matrix deposition are being initiated, FN mRNA levels and the relative rates of FN synthesis become progressively about 4-fold higher than in the distal subridge region, which consists of undifferentiated mesenchymal cells that have not yet initiated condensation.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Correction: In vitro–in vivo evaluation of hyaluronic acid-based amphiphilic copolymers for tumour targeted delivery: the role of hydrophobic groups

RSC Advances ◽  
2017 ◽  
Vol 7 (48) ◽  
pp. 30049-30050
Author(s):  
Zhihong Zhu ◽  
Dongyang Li ◽  
Yuenan Li ◽  
Xinggang Yang ◽  
Weisan Pan
Keyword(s):  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Amphiphilic Copolymers ◽  
In Vivo Evaluation

Correction for ‘In vitro–in vivo evaluation of hyaluronic acid-based amphiphilic copolymers for tumour targeted delivery: the role of hydrophobic groups’ by Zhihong Zhu et al., RSC Adv., 2017, 7, 23942–23953.

scholarly journals Folate-conjugated hydrophobicity modified glycol chitosan nanoparticles for targeted delivery of methotrexate in rheumatoid arthritis

2020 ◽  
Vol 18 ◽  
pp. 228080002096262 ◽  
Author(s):  
Zhongqing Wu ◽  
Kanna Xu ◽  
Jikang Min ◽  
Minchang Chen ◽  
Liping Shen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Delivery ◽  
Chitosan Nanoparticles ◽  
Autoimmune Disorder ◽  
Glycol Chitosan ◽  
Hydrophobically Modified ◽  
Superior Efficacy ◽  
Transmission Electron

Background: Targeted delivery to the Rheumatoid arthritis (RA) which is characterized by destruction and degeneration of bones due to chronic inflammation is of great need. RA being a chronic autoimmune disorder might result in severe disability and morbidity. A targeted delivery system is designed to deliver methotrexate (MTX) for RA. Methods: Here, we synthesized folic acid (FA) conjugated hydrophobically modified glycol chitosan (GC) self-assembled nanoparticles (FA-GC-SA) for the targeted delivery of MTX to RA. The FA conjugation and hydrophobic modification of GC by stearic acid (SA) was confirmed by Fourier-transform infrared spectroscopy (FTIR). The FA-GC-SA was exploited for developing targeted nanoparticles encapsulating MTX by the ionic gelation method. The particles were characterized and evaluated for their targeting potential in in vitro cell culture studies. Further their in vivo efficacy in arthritis induced rats using collagen was also evaluated. Results: FTIR confirms the successful modification of GC-SA and FA-GC-SA. The FA-GC-SA-MTX of size 153 ± 9 nm were prepared with high encapsulation efficiency of MTX. The FA-GC-SA-MTX size was further confirmed by transmission electron microscopy (TEM). In vitro cell studies revealed the superior efficacy of FA-GC-SA-MTX in cell cytotoxicity. Also, significantly higher cellular uptake of FA functionalized FA-GC-SA-MTX was observed in comparison to non-functionalized GC-SA-MTX attributed to folate receptors (FRs) mediated endocytosis. In vivo results confirms the potential of FA-GC-SA-MTX which reduces reduces the pro-inflammatory cytokines, paw thickness, and arthritis score in collagen induced rats. Conclusion: The results shows that FRs targeted FA-GC-SA-MTX has superior efficacy in the treatment of RA.

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