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Development of polymeric-cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery.

Jain AK, Massey A, Yusuf H, McDonald DM, McCarthy HO, Kett VL - Int J Nanomedicine (2015)

Bottom Line: The best formulation was selected and was able to transfect cells while maintaining viability.The effect of transferrin-appended composite nanoparticles was also studied.Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK ; Weatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK.

ABSTRACT
We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

No MeSH data available.


Related in: MedlinePlus

TEM images.Notes: (A) RNPs; (B and C) PLA10-PEG2 composite nanoparticles; (D and E) PLA25-PEG5 composite nanoparticles; and (F and G) PLA50-PEG5 composite nanoparticles. Magnification of each image is shown in the bottom-right corner. The original value of nanoparticle size in panel A is 30.85 nm instead of 30.05 nm.Abbreviations: TEM, transmission electron microscopy; RNPs, RALA nanoparticles; PLA, polylactic acid; PEG, polyethylene glycol.
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f5-ijn-10-7183: TEM images.Notes: (A) RNPs; (B and C) PLA10-PEG2 composite nanoparticles; (D and E) PLA25-PEG5 composite nanoparticles; and (F and G) PLA50-PEG5 composite nanoparticles. Magnification of each image is shown in the bottom-right corner. The original value of nanoparticle size in panel A is 30.85 nm instead of 30.05 nm.Abbreviations: TEM, transmission electron microscopy; RNPs, RALA nanoparticles; PLA, polylactic acid; PEG, polyethylene glycol.

Mentions: A new approach was developed whereby the hydrophobic dye osmium tetroxide was added to the polymeric organic phase during the preparation of the composite nanoparticles. The dye becomes molecularly dispersed in the polymer matrix only, giving a contrast background to the RNPs that makes them visible inside the composite nanoparticles (Figure 5). To our knowledge, this is the first time that this preparation method has been reported. The images show that the RNPs were spherical and ≤50 nm (Figure 5A). RNPs are the bright areas in the center of the composite nanoparticles. These images give visual confirmation of RNP encapsulation inside the composite nanoparticles. Depending on the size, single or multiple RNPs are encapsulated within the composite nanoparticles.


Development of polymeric-cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery.

Jain AK, Massey A, Yusuf H, McDonald DM, McCarthy HO, Kett VL - Int J Nanomedicine (2015)

TEM images.Notes: (A) RNPs; (B and C) PLA10-PEG2 composite nanoparticles; (D and E) PLA25-PEG5 composite nanoparticles; and (F and G) PLA50-PEG5 composite nanoparticles. Magnification of each image is shown in the bottom-right corner. The original value of nanoparticle size in panel A is 30.85 nm instead of 30.05 nm.Abbreviations: TEM, transmission electron microscopy; RNPs, RALA nanoparticles; PLA, polylactic acid; PEG, polyethylene glycol.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664533&req=5

f5-ijn-10-7183: TEM images.Notes: (A) RNPs; (B and C) PLA10-PEG2 composite nanoparticles; (D and E) PLA25-PEG5 composite nanoparticles; and (F and G) PLA50-PEG5 composite nanoparticles. Magnification of each image is shown in the bottom-right corner. The original value of nanoparticle size in panel A is 30.85 nm instead of 30.05 nm.Abbreviations: TEM, transmission electron microscopy; RNPs, RALA nanoparticles; PLA, polylactic acid; PEG, polyethylene glycol.
Mentions: A new approach was developed whereby the hydrophobic dye osmium tetroxide was added to the polymeric organic phase during the preparation of the composite nanoparticles. The dye becomes molecularly dispersed in the polymer matrix only, giving a contrast background to the RNPs that makes them visible inside the composite nanoparticles (Figure 5). To our knowledge, this is the first time that this preparation method has been reported. The images show that the RNPs were spherical and ≤50 nm (Figure 5A). RNPs are the bright areas in the center of the composite nanoparticles. These images give visual confirmation of RNP encapsulation inside the composite nanoparticles. Depending on the size, single or multiple RNPs are encapsulated within the composite nanoparticles.

Bottom Line: The best formulation was selected and was able to transfect cells while maintaining viability.The effect of transferrin-appended composite nanoparticles was also studied.Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK ; Weatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK.

ABSTRACT
We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

No MeSH data available.


Related in: MedlinePlus