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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

In vitro release study showing rate of DNA release from composite nanoparticles.Notes: Each point is mean ± SD (n=4). SD is shown as either positive or negative error bars to aid better presentation of data.Abbreviations: SD, standard deviation; PLA, polylactic acid; PEG, polyethylene glycol.
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f6-ijn-10-7183: In vitro release study showing rate of DNA release from composite nanoparticles.Notes: Each point is mean ± SD (n=4). SD is shown as either positive or negative error bars to aid better presentation of data.Abbreviations: SD, standard deviation; PLA, polylactic acid; PEG, polyethylene glycol.

Mentions: All the composite nanoparticles exhibited an initial burst release that accounted for the 8%–10% DNA released in first 24 hours, which is good for the priming of a therapeutic response (Figure 6). Four to five percent of this was DNA that had been released during freeze-drying as determined by centrifugation. The PLAx-PEG5 copolymers exhibited a larger burst release than PLA20-PEG2, which could be attributed to the longer PEG chains of the PLAx-PEG5 formulations since it is known that higher contact area with water enhances degradation rate.45 PLA25-PEG5 showed the highest amount of DNA release at every time point, which was attributed to a number of factors, longer PEG chains, shorter PLA chains, and the low Tg, which was closest to the temperature of the release medium. The longer PEG chains might have caused a higher degradation rate in this system, and increased PEG content has been correlated with increase in cargo release.46 The other two formulations have a higher ratio of PLA chain length to PEG, which slows the degradation profile. All three composite nanoparticles were deemed acceptable. The PLA25-PEG5 was taken forward for the transfection study because of its higher release rate.


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)

In vitro release study showing rate of DNA release from composite nanoparticles.Notes: Each point is mean ± SD (n=4). SD is shown as either positive or negative error bars to aid better presentation of data.Abbreviations: SD, standard deviation; PLA, polylactic acid; PEG, polyethylene glycol.
© Copyright Policy
Related In: Results  -  Collection

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

f6-ijn-10-7183: In vitro release study showing rate of DNA release from composite nanoparticles.Notes: Each point is mean ± SD (n=4). SD is shown as either positive or negative error bars to aid better presentation of data.Abbreviations: SD, standard deviation; PLA, polylactic acid; PEG, polyethylene glycol.
Mentions: All the composite nanoparticles exhibited an initial burst release that accounted for the 8%–10% DNA released in first 24 hours, which is good for the priming of a therapeutic response (Figure 6). Four to five percent of this was DNA that had been released during freeze-drying as determined by centrifugation. The PLAx-PEG5 copolymers exhibited a larger burst release than PLA20-PEG2, which could be attributed to the longer PEG chains of the PLAx-PEG5 formulations since it is known that higher contact area with water enhances degradation rate.45 PLA25-PEG5 showed the highest amount of DNA release at every time point, which was attributed to a number of factors, longer PEG chains, shorter PLA chains, and the low Tg, which was closest to the temperature of the release medium. The longer PEG chains might have caused a higher degradation rate in this system, and increased PEG content has been correlated with increase in cargo release.46 The other two formulations have a higher ratio of PLA chain length to PEG, which slows the degradation profile. All three composite nanoparticles were deemed acceptable. The PLA25-PEG5 was taken forward for the transfection study because of its higher release rate.

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