Co‐delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)‐
- Award ID(s):
- 1703438
- PAR ID:
- 10328481
- Date Published:
- Journal Name:
- Pharmaceutics
- Volume:
- 13
- Issue:
- 8
- ISSN:
- 1999-4923
- Page Range / eLocation ID:
- 1131
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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block ‐poly(lactic‐co ‐glycolic acid) (PEG–PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA‐containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG‐CNA‐PLGA are synthesized and then formulated into polymer nanoparticles from oil‐in‐water emulsions. The CNA‐containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG‐PLGA alone shows minimal DNA loading, and non‐complementary DNA strands do not get encapsulated within the PEG‐CNA‐PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co‐loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA‐containing particles as carriers for chemotherapy agents and gene silencers. -
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Abstract Polylactic‐co‐glycolic acid (PLGA)‐basedpolymers are synthetic materials that are prominent in drug delivery. PLGA homopolymer is biodegradable, biocompatible and is often polymerized to polyethylene glycol (PEG) to form a block copolymer used to form core‐shell nanoparticles. PEG is known for reducing blood clearance and opsonization, in addition to imparting “stealth” properties to various drugs and biomaterials. Current formulation methodologies for PLGA–PEG copolymer nanoparticles can be tuned to control key parameters for improved therapeutic delivery; however, molecular‐level understanding of copolymer‐solvent interactions during nanoparticle formulation is lacking. Therefore, three different PLGA–PEG/solvent pairs are examined, in comparison to their homopolymer constituents, to better understand copolymerization effects and its impact on nanoparticle formulation. Results show that at room temperature PLGA–PEG oligomers in dimethyl sulfoxide are the most rigid in good solvent conditions (Flory exponent >0.5) and have the largest end‐to‐end relaxation times when compared to acetone and water. PEG has a Flory exponent of ~0.5 in both water and acetone, showing that the molecular dynamic model that is employed can reproduce its amphiphilic nature in solution. Knowledge of PLGA–PEG structure and dynamics can be used in the design of novel biomedical technologies that improve drug efficacy and reduce cost of treatment.
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/pharmaceutics13081131
