Concanavalin A-conjugated poly(ethylene glycol)–poly(lactic acid) nanoparticles for intranasal drug delivery to the cervical lymph nodes

Shao, Xia; Li, Qingfeng; Zhang, Chi; Zheng, Xiaoyao; Chen, Jie; Zha, Yuan; Qian, Yong; Zhang, Xi; Zhang, Qizhi; Jiang, Xinguo

doi:10.3109/02652048.2013.788086

Cited by 11 publications

(7 citation statements)

References 28 publications

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“…Con A–conjugated poly(ethylene glycol)-poly(lactic acid) NPs (Con A-NPs) have been developed for intranasal medication delivery to cervical lymph nodes. Con A–conjugated NPs preserved their ability to bind to particular glycans and boost cellular absorption at a faster rate (Table 2 ) [ 132 ]. Ali et al demonstrated the bio-conjugation of Con A to glycoenzyme horseradish peroxidase (HRP) inside single nanopores and fabricated in heavy ion tracked polymer membranes.…”

Section: Lectins As Drug Carrier Systemsmentioning

confidence: 99%

Applications of mannose-binding lectins and mannan glycoconjugates in nanomedicine

Gupta

2022

J Nanopart Res

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Glycosylated nanoparticles (NPs) have drawn a lot of attention in the biomedical field over the past few decades, particularly in applications like targeted drug delivery. Mannosylated NPs and mannan-binding lectins/proteins (MBL/MBP) are emerging as promising tools for delivery of drugs, medicines, and enzymes to targeted tissues and cells as nanocarriers, enhancing their therapeutic benefits while avoiding the adverse effects of the drug. The occurrence of plenty of lectin receptors and their mannan ligands on cell surfaces makes them multifaceted carriers appropriate for specific delivery of bioactive drug materials to their targeted sites. Thus, the present review describes the tethering of mannose (Man) to several nanostructures, like micelles, liposomes, and other NPs, applicable for drug delivery systems. Bioadhesion through MBL-like receptors on cells has involvements applicable to additional arenas of science, for example gene delivery, tissue engineering, biomaterials, and nanotechnology. This review also focuses on the role of various aspects of drug/antigen delivery using (i) mannosylated NPs, (ii) mannosylated lectins, (iii) amphiphilic glycopolymer NPs, and (iv) natural mannan-containing polysaccharides, with most significant applications of MBL-based NPs as multivalent scaffolds, using different strategies. Graphical abstract Mannosylated NPs and/or MBL/MBP are coming up as viable and versatile tools as nanocarriers to deliver drugs and enzymes precisely to their target tissues or cells. The presence of abundant number of lectin receptors and their mannan ligands on cell surfaces makes them versatile carriers suitable for the targeted delivery of bioactive drugs.

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Section: Lectins As Drug Carrier Systemsmentioning

confidence: 99%

Applications of mannose-binding lectins and mannan glycoconjugates in nanomedicine

Gupta

2022

J Nanopart Res

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“…An accurate substitution ratio (SA to LMWH) can be determined from the 1 H-NMR spectrum of the physical mixtures of LMWH and SA. In our previous study, 45 the correlation of the molar ratio of arachidic acid to chitosan oligosaccharide (CSO) was evaluated using 1 H-NMR from a physical mixture of arachidic acid and CSO in DMSO-d 6 . However, LMWH has a strong hydrophilic property, while SA has a strong hydrophobic property; thus, an NMR cosolvent consisting of D 2 O and THF-d 8 was used to dissolve LMWH and SA.…”

Section: Discussionmentioning

confidence: 99%

“…The dissolution medium was phosphatebuffered saline (PBS, pH: 7.4) containing 0.5% (w/v) Tween 80 at 37°C, and was rotated at 50 rpm. Aliquots (0.2 mL) of medium were collected at predetermined times (1,2,3,4,6,9,12,24,48,72,96, and 144 hours), and fresh media (37°C) of equal volume was added to maintain sink condition. The amounts of DCT released into the medium were analyzed by HPLC.…”

Section: In Vitro Dct Release Studiesmentioning

confidence: 99%

“…3,4 Additionally, these nanoparticulate drugs offer the advantages of prolonged systemic circulation by avoiding phagocytosis, improved efficacy, and reduced toxicity. Numerous biocompatible and biodegradable materials, such as poly(lactic acid), 5,6 poly(glycolic acid), 7 polycaprolactone, 8,9 polysaccharides, 10 proteins, 11 and polypeptides, 12 have been used for the preparation of polymeric nanoparticles. Among them, polysaccharides have been used extensively to prepare nanoparticles for drug delivery.…”

Section: Introductionmentioning

confidence: 99%

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Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel

Kim¹,

Termsarasab²,

Cho³

et al. 2014

IJN

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Low-molecular-weight heparin (LMWH)–stearylamine (SA) conjugates (LHSA)-based self-assembled nanoparticles were prepared for intravenous delivery of docetaxel (DCT). 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide and N -hydroxysuccinimide were used as coupling agents for synthesis of LHSA conjugates. The physicochemical properties, in vitro antitumor efficacy, in vitro cellular uptake efficiency, in vivo antitumor efficacy, and in vivo pharmacokinetics of LHSA nanoparticles were investigated. The LHSA nanoparticles exhibited a spherical shape with a mean diameter of 140–180 nm and a negative surface charge. According to in vitro release and in vivo pharmacokinetic test results, the docetaxel-loaded LHSA5 (LMWH:SA =1:5) nanoparticles exhibited sustained drug release profiles. The blank LHSA nanoparticles demonstrated only an insignificant cytotoxicity in MCF-7 and MDAMB 231 human breast cancer cells; additionally, higher cellular uptake of coumarin 6 (C6) in MCF-7 and MDAMB 231 cells was observed in the LHSA5 nanoparticles group than that in the C6 solution group. The in vivo tumor growth inhibition efficacy of docetaxel-loaded LHSA5 nanoparticles was also significantly higher than the Taxotere ® -treated group in the MDAMB 231 tumor-xenografted mouse model. These results indicated that the LHSA5-based nanoparticles could be a promising anticancer drug delivery system.

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“…In the previous study, retention of the doxorubicin-conjugated dendrimer in lymph nodes was suggested to occur via physical entrapment of the polymer within lymph nodes. This strategy may be further enhanced by employing drug carriers that target lymph node resident macrophages. − This can be accomplished via the conjugation of macrophage targeting ligands, such as mannose, to the carrier surface, or by increasing surface charge to promote recognition of the carrier by both the lymph node parenchyma and lymph node resident macrophages.…”

Section: Introductionmentioning

confidence: 99%

Methotrexate-Conjugated PEGylated Dendrimers Show Differential Patterns of Deposition and Activity in Tumor-Burdened Lymph Nodes after Intravenous and Subcutaneous Administration in Rats

et al. 2015

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The current study sought to explore whether the subcutaneous administration of lymph targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumor activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumor-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumor growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumor-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumor activity, possibly suggesting constrained drug release at the site of action.

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Concanavalin A-conjugated poly(ethylene glycol)–poly(lactic acid) nanoparticles for intranasal drug delivery to the cervical lymph nodes

Cited by 11 publications

References 28 publications

Applications of mannose-binding lectins and mannan glycoconjugates in nanomedicine

Applications of mannose-binding lectins and mannan glycoconjugates in nanomedicine

Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel

Methotrexate-Conjugated PEGylated Dendrimers Show Differential Patterns of Deposition and Activity in Tumor-Burdened Lymph Nodes after Intravenous and Subcutaneous Administration in Rats

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