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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.


Thermal transitions of the bulk copolymers and nanoparticles.Note: MTDSC curves showing Tg regions of the composite nanoparticles prepared with copolymers as indicated (A) and Tg regions of the bulk copolymers (B).Abbreviations: MTDSC, modulated temperature differential scanning calorimetry; PLA, polylactic acid; PEG, polyethylene glycol.
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f3-ijn-10-7183: Thermal transitions of the bulk copolymers and nanoparticles.Note: MTDSC curves showing Tg regions of the composite nanoparticles prepared with copolymers as indicated (A) and Tg regions of the bulk copolymers (B).Abbreviations: MTDSC, modulated temperature differential scanning calorimetry; PLA, polylactic acid; PEG, polyethylene glycol.

Mentions: All products exhibited a Tg at 120°C, indicating that the trehalose was present in the amorphous state (Figure 3A),41 which is desirable since crystallization of protectants in nanoparticle formulations has been shown to cause instability.42 The Tg values of composite nanoparticles were found to be higher than those of their respective copolymers (Figure 3B), which was attributed to the more confined architecture of the polymer chains within the composite nanoparticles than in the bulk polymer.43,44 A relatively small Tg increase was seen for the Tg value of PLA20-PEG2 nanoparticles compared with the bulk polymer indicating that other factors are also involved in determining the value of Tg, which could be interesting to explore in future studies.


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)

Thermal transitions of the bulk copolymers and nanoparticles.Note: MTDSC curves showing Tg regions of the composite nanoparticles prepared with copolymers as indicated (A) and Tg regions of the bulk copolymers (B).Abbreviations: MTDSC, modulated temperature differential scanning calorimetry; PLA, polylactic acid; PEG, polyethylene glycol.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-10-7183: Thermal transitions of the bulk copolymers and nanoparticles.Note: MTDSC curves showing Tg regions of the composite nanoparticles prepared with copolymers as indicated (A) and Tg regions of the bulk copolymers (B).Abbreviations: MTDSC, modulated temperature differential scanning calorimetry; PLA, polylactic acid; PEG, polyethylene glycol.
Mentions: All products exhibited a Tg at 120°C, indicating that the trehalose was present in the amorphous state (Figure 3A),41 which is desirable since crystallization of protectants in nanoparticle formulations has been shown to cause instability.42 The Tg values of composite nanoparticles were found to be higher than those of their respective copolymers (Figure 3B), which was attributed to the more confined architecture of the polymer chains within the composite nanoparticles than in the bulk polymer.43,44 A relatively small Tg increase was seen for the Tg value of PLA20-PEG2 nanoparticles compared with the bulk polymer indicating that other factors are also involved in determining the value of Tg, which could be interesting to explore in future studies.

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.