Reconstitutable charged polymeric (PLGA)2-b-PEI micelles for gene therapeutics delivery

Deepa Mishra; Han Chang Kang; You Han Bae

doi:10.1016/j.biomaterials.2011.01.077

Reconstitutable charged polymeric (PLGA)₂-b-PEI micelles for gene therapeutics delivery

Deepa Mishra, Han Chang Kang, You Han Bae

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

This study investigated the potential of creating a charged polymeric micelle-based nucleic acid delivery system that could easily be reconstituted by the addition of water. (PLGA_36kDa)₂-b-bPEI_25kDa (PLGA MW 36 kDa, bPEI M_w 25 kDa, PLGA:bPEI block ratio = 2) was synthesized and used to prepare cationic micelles. The copolymer retained proton-buffering capability from the bPEI block within the endosomal pH range. Micelle/pDNA complexes retained their particle size (100-150 nm) and surface charge (30-40 mV) following reconstitution. It was found that adding a small amount of low molecular weight bPEI (1.8 kDa) completely shielded pDNA in the micelle/pDNA complexes and enhanced transfection efficiency 50-100 fold for both fresh and reconstituted complexes without affecting complex size. Transfection efficiency for " reconstituted" micelle/pDNA/bPEI_1.8kDa (WR 1) complexes was 16-fold higher than its " fresh" counterpart. Although transfection levels achieved using " reconstituted" micelle/pDNA/bPEI_1.8kDa complexes were 3.6-fold lower than control " fresh" bPEI_25kDa/pDNA (N/P 5) complexes, transfection levels were 39-fold higher than " reconstituted" bPEI_25kDa/pDNA (N/P 5) complexes. The micelle/pDNA/bPEI_1.8kDa system showed very low cytotoxicity in MCF7 cells even with pDNA doses up to 20 μg, and transfection levels increased linearly with increasing pDNA dose. These results indicate that this PLGA-b-bPEI polymeric micelle-based system is well suited as a reconstitutable gene delivery system, and has high potential for use as a delivery system for gene therapy applications.

Original language	English
Pages (from-to)	3845-3854
Number of pages	10
Journal	Biomaterials
Volume	32
Issue number	15
DOIs	https://doi.org/10.1016/j.biomaterials.2011.01.077
State	Published - May 2011

Bibliographical note

Funding Information:
This work was partially supported by NIH GM82866 . Utah-Inha DDS Center supported DM for one year.

Keywords

Layer-by-layer
Poly(lactide-co-glycolide)
Polyethyleneimine
Polymeric gene delivery
Polymeric micelles
Reconstitution

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10.1016/j.biomaterials.2011.01.077

Cite this

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title = "Reconstitutable charged polymeric (PLGA)2-b-PEI micelles for gene therapeutics delivery",

abstract = "This study investigated the potential of creating a charged polymeric micelle-based nucleic acid delivery system that could easily be reconstituted by the addition of water. (PLGA36kDa)2-b-bPEI25kDa (PLGA MW 36 kDa, bPEI Mw 25 kDa, PLGA:bPEI block ratio = 2) was synthesized and used to prepare cationic micelles. The copolymer retained proton-buffering capability from the bPEI block within the endosomal pH range. Micelle/pDNA complexes retained their particle size (100-150 nm) and surface charge (30-40 mV) following reconstitution. It was found that adding a small amount of low molecular weight bPEI (1.8 kDa) completely shielded pDNA in the micelle/pDNA complexes and enhanced transfection efficiency 50-100 fold for both fresh and reconstituted complexes without affecting complex size. Transfection efficiency for {"} reconstituted{"} micelle/pDNA/bPEI1.8kDa (WR 1) complexes was 16-fold higher than its {"} fresh{"} counterpart. Although transfection levels achieved using {"} reconstituted{"} micelle/pDNA/bPEI1.8kDa complexes were 3.6-fold lower than control {"} fresh{"} bPEI25kDa/pDNA (N/P 5) complexes, transfection levels were 39-fold higher than {"} reconstituted{"} bPEI25kDa/pDNA (N/P 5) complexes. The micelle/pDNA/bPEI1.8kDa system showed very low cytotoxicity in MCF7 cells even with pDNA doses up to 20 μg, and transfection levels increased linearly with increasing pDNA dose. These results indicate that this PLGA-b-bPEI polymeric micelle-based system is well suited as a reconstitutable gene delivery system, and has high potential for use as a delivery system for gene therapy applications.",

keywords = "Layer-by-layer, Poly(lactide-co-glycolide), Polyethyleneimine, Polymeric gene delivery, Polymeric micelles, Reconstitution",

author = "Deepa Mishra and Kang, {Han Chang} and Bae, {You Han}",

note = "Funding Information: This work was partially supported by NIH GM82866 . Utah-Inha DDS Center supported DM for one year. ",

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language = "English",

volume = "32",

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T1 - Reconstitutable charged polymeric (PLGA)2-b-PEI micelles for gene therapeutics delivery

AU - Mishra, Deepa

AU - Kang, Han Chang

AU - Bae, You Han

N1 - Funding Information: This work was partially supported by NIH GM82866 . Utah-Inha DDS Center supported DM for one year.

PY - 2011/5

Y1 - 2011/5

N2 - This study investigated the potential of creating a charged polymeric micelle-based nucleic acid delivery system that could easily be reconstituted by the addition of water. (PLGA36kDa)2-b-bPEI25kDa (PLGA MW 36 kDa, bPEI Mw 25 kDa, PLGA:bPEI block ratio = 2) was synthesized and used to prepare cationic micelles. The copolymer retained proton-buffering capability from the bPEI block within the endosomal pH range. Micelle/pDNA complexes retained their particle size (100-150 nm) and surface charge (30-40 mV) following reconstitution. It was found that adding a small amount of low molecular weight bPEI (1.8 kDa) completely shielded pDNA in the micelle/pDNA complexes and enhanced transfection efficiency 50-100 fold for both fresh and reconstituted complexes without affecting complex size. Transfection efficiency for " reconstituted" micelle/pDNA/bPEI1.8kDa (WR 1) complexes was 16-fold higher than its " fresh" counterpart. Although transfection levels achieved using " reconstituted" micelle/pDNA/bPEI1.8kDa complexes were 3.6-fold lower than control " fresh" bPEI25kDa/pDNA (N/P 5) complexes, transfection levels were 39-fold higher than " reconstituted" bPEI25kDa/pDNA (N/P 5) complexes. The micelle/pDNA/bPEI1.8kDa system showed very low cytotoxicity in MCF7 cells even with pDNA doses up to 20 μg, and transfection levels increased linearly with increasing pDNA dose. These results indicate that this PLGA-b-bPEI polymeric micelle-based system is well suited as a reconstitutable gene delivery system, and has high potential for use as a delivery system for gene therapy applications.

AB - This study investigated the potential of creating a charged polymeric micelle-based nucleic acid delivery system that could easily be reconstituted by the addition of water. (PLGA36kDa)2-b-bPEI25kDa (PLGA MW 36 kDa, bPEI Mw 25 kDa, PLGA:bPEI block ratio = 2) was synthesized and used to prepare cationic micelles. The copolymer retained proton-buffering capability from the bPEI block within the endosomal pH range. Micelle/pDNA complexes retained their particle size (100-150 nm) and surface charge (30-40 mV) following reconstitution. It was found that adding a small amount of low molecular weight bPEI (1.8 kDa) completely shielded pDNA in the micelle/pDNA complexes and enhanced transfection efficiency 50-100 fold for both fresh and reconstituted complexes without affecting complex size. Transfection efficiency for " reconstituted" micelle/pDNA/bPEI1.8kDa (WR 1) complexes was 16-fold higher than its " fresh" counterpart. Although transfection levels achieved using " reconstituted" micelle/pDNA/bPEI1.8kDa complexes were 3.6-fold lower than control " fresh" bPEI25kDa/pDNA (N/P 5) complexes, transfection levels were 39-fold higher than " reconstituted" bPEI25kDa/pDNA (N/P 5) complexes. The micelle/pDNA/bPEI1.8kDa system showed very low cytotoxicity in MCF7 cells even with pDNA doses up to 20 μg, and transfection levels increased linearly with increasing pDNA dose. These results indicate that this PLGA-b-bPEI polymeric micelle-based system is well suited as a reconstitutable gene delivery system, and has high potential for use as a delivery system for gene therapy applications.

KW - Layer-by-layer

KW - Poly(lactide-co-glycolide)

KW - Polyethyleneimine

KW - Polymeric gene delivery

KW - Polymeric micelles

KW - Reconstitution

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DO - 10.1016/j.biomaterials.2011.01.077

M3 - Article

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SN - 0142-9612

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JO - Biomaterials

JF - Biomaterials

IS - 15

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