A novel tumor-targeted delivery system with hydrophobized hyaluronic acid–spermine conjugates (HHSCs) for efficient receptor-mediated siRNA delivery

Shen, Yan; Wang, Buhai; Lu, Yang; Ouahab, Ammar; Li, Qian; Tu, Jiasheng

doi:10.1016/j.ijpharm.2011.04.049

Cited by 49 publications

(31 citation statements)

References 44 publications

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“…The resulting polymers can then self-assemble into micelles in physiological conditions. 21,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] Similarly, CS has been chemically modified forming, for example, quaternary ammonium palmitoyl glycochitosan (GCPQ), which induces the formation of micelles upon dispersion in water. 72,73 The hydrophobic part of copolymer is oriented inwards, forming a core suited for the encapsulation of hydrophobic drugs.…”

Section: Ha and Cs-based Micellesmentioning

confidence: 99%

“…For example, Shen et al developed siRNA-loaded HA micelles in which low Mw HA was conjugated with hydrophobic alkylamines and spermines. 21,54 Here the hydrophobic and cationic spermine formed a hydrophobic core within which the oligonucleotide was condensed, due to the polycationic nature of spermine, thus protecting the genetic material from enzymatic degradation. This resulted in improved transfection and gene silencing in cancer cells when compared to other established transfection agents like lipofectamine and polyethyleneimine.…”

Section: Gene Deliverymentioning

confidence: 99%

“…The main limitation of HA for gene therapy relies on its polyanionic nature, making it incapable of condensing oligonucleotides. To address this, researchers are trying to synthesize HA derivatives bearing cationic groups, 21,54,65,68 or to engineer nanocarriers combining HA with other cationic condensing agents. 21,54,65,68 Ocular drug delivery is often seen as a niche application, but its industrial interest has grown steadily in the last decade; many drugs would benefit from improved retention on the ocular surface, and enhanced corneal and conjunctival penetration.…”

Section: Comparative Analysis Of the Potential Of Cs And Ha-based Nanmentioning

confidence: 99%

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Polysaccharide-Based Nanocarriers for Drug Delivery

Teijeiro¹,

McGlone²,

Csaba³

et al. 2014

Frontiers in Nanobiomedical Research

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Section: Ha and Cs-based Micellesmentioning

confidence: 99%

Section: Gene Deliverymentioning

confidence: 99%

Section: Comparative Analysis Of the Potential Of Cs And Ha-based Nanmentioning

confidence: 99%

See 1 more Smart Citation

Polysaccharide-Based Nanocarriers for Drug Delivery

Teijeiro¹,

McGlone²,

Csaba³

et al. 2014

Frontiers in Nanobiomedical Research

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“…siRNA/PEI-HA complexes could be successfully taken up by B16F cells, and a PGL3-Luc gene silencing effect can be achieved when cells were transfected with anti-PGL-Luc siRNA/PEI-HA complexes (38, 39). Cyclooxygenase-2 (COX-2) siRNA encapsulated in hydrophobized HA-spermine conjugate (HHSC) could be taken up by gastric cancer SGC-7901 cells and subsequently down-regulated COX-2 gene expression (42). HA-decorated PLGA-PEG nanoparticles were constructed for the targeted delivery of SN-38 to ovarian cancer (9).…”

Section: Discussionmentioning

confidence: 99%

Cluster of Differentiation 44 Targeted Hyaluronic Acid Based Nanoparticles for MDR1 siRNA Delivery to Overcome Drug Resistance in Ovarian Cancer

et al. 2014

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Purpose Approaches for the synthesis of biomaterials to facilitate the delivery of “biologics” is a major area of research in cancer therapy. Here we designed and characterized a hyaluronic acid (HA) based self-assembling nanoparticles that can target CD44 receptors overexpressed on multidrug resistance (MDR) ovarian cancer. The nanoparticle system is composed of HA-poly(ethyleneimine)/HA-poly(ethylene glycol) (HA-PEI/HA-PEG) designed to deliver MDR1 siRNA for the treatment of MDR in an ovarian cancer model. Methods HA-PEI/HA-PEG nanoparticles were synthesized and characterized, then the cellular uptake and knockdown efficiency of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles was further determined. A human xenograft MDR ovarian cancer model was established to evaluate the effects of the combination of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles and paclitaxel on MDR tumor growth. Results Our results demonstrated that HA-PEI/HA-PEG nanoparticles successfully targeted CD44 and delivered MDR1 siRNA into OVCAR8TR (established paclitaxel resistant) tumors. Additionally, HA-PEI/HA-PEG nanoparticles loaded with MDR1 siRNA efficiently down-regulated the expression of MDR1 and P-glycoprotein (Pgp), inhibited the functional activity of Pgp, and subsequently increased cell sensitivity to paclitaxel. HA-PEI/HA-PEG/MDR1 siRNA nanoparticle therapy followed by paclitaxel treatment inhibited tumor growth in MDR ovarian cancer mouse models. Conclusions These findings suggest that this CD44 targeted HA-PEI/HA-PEG nanoparticle platform may be a clinicaly relevant gene delivery system for systemic siRNA-based anticancer therapeutics for the treatment of MDR cancers.

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“…A formulação com heparina foi deixada em banho termostatizado a 37 °C por uma hora, para que ocorresse a descomplexação do siRNA, seguindo o método proposto por Shen et al (2011). Foram testados diferentes volumes de solução de heparina a ser adicionado para promover a descomplexação, sendo que 10 µL de solução de heparina sódica (5.000 U.I./mL) foi adequado para este propósito.…”

Section: Avaliação Da Estabilidade Do Sirna Complexado Nas Formulaçõeunclassified

Sistemas de liberação de geleificação in situ para veiculação de siRNA: desenvolvimento, caracterização e estudos in vitro e in vivo em modelo animal

Cardoso¹

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The evidence that siRNA can be used for suppression of genes in different mammalian cells attracted wide attention as a new possibility of treatment for various diseases. However, for siRNA therapeutic application is necessary to develop an effective non-toxic delivery system, which facilitate the siRNA cell uptake and avoid its degradation by enzymes. The genes suppression promoted by siRNA depends on the number of siRNA molecules transfected as the cell replication rate. One of the dosage forms that have been widely used in literature in order to prolong and protect the drug release is the in situ gelling formulations. Thus, the present study aimed the development and characterization of the in situ gelling liquid crystal-based systems for subcutaneous application of siRNA in gene therapy. Appropriate mixtures of monoolein, propylene glycol, Tris buffer and polyethyleneimine or oleylamine (cationic polymer and lipid, respectively) was able to form precursor formulation that gelling in water excess and, as demonstrated by the swelling studies, the gel formation is a fast process. The developed formulations were also effective for complexing the siRNA, indicating the importance of the incorporation of cationic additives in the systems. The in vitro release study showed that the release is dependent on the water absorption rate. In vivo studies in animal models have shown the gel is formed in vivo after water uptake of body fluids, and it is biodegradable and biocompatible. The systems developed are promising for the treatment of diseases where the local and sustained administration of siRNA is necessary.

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A novel tumor-targeted delivery system with hydrophobized hyaluronic acid–spermine conjugates (HHSCs) for efficient receptor-mediated siRNA delivery

Cited by 49 publications

References 44 publications

Polysaccharide-Based Nanocarriers for Drug Delivery

Polysaccharide-Based Nanocarriers for Drug Delivery

Cluster of Differentiation 44 Targeted Hyaluronic Acid Based Nanoparticles for MDR1 siRNA Delivery to Overcome Drug Resistance in Ovarian Cancer

Sistemas de liberação de geleificação in situ para veiculação de siRNA: desenvolvimento, caracterização e estudos in vitro e in vivo em modelo animal

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