期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 12, 期 -, 页码 3913-3926出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S134833
关键词
cisplatin; drug delivery; cancer chemotherapy; polymer; poly(lactic-co-glycolicacid); nanoparticles; electrohydrodynamic atomization; controlled release
资金
- Engineering and Physical Sciences Research Council (EPSRC) [EP/L026287/1, EP/L025825/1]
- EPSRC [EP/L026287/1, EP/L025825/1] Funding Source: UKRI
- MRC [G1001497] Funding Source: UKRI
- Cancer Research UK [16463, 21030] Funding Source: researchfish
- Cancer Research UK
- Versus Arthritis [20265] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/L025825/1, EP/L026287/1] Funding Source: researchfish
- Medical Research Council [1252897, G1001497] Funding Source: researchfish
Increasing the clinical efficacy of toxic chemotherapy drugs such as cisplatin (CDDP), via targeted drug delivery, is a key area of research in cancer treatment. In this study, CDDP-loaded poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NPs) were successfully prepared using electrohydrodynamic atomization (EHDA). The configuration was varied to control the distribution of CDDP within the particles, and high encapsulation efficiency (>70%) of the drug was achieved. NPs were produced with either a core-shell (CS) or a matrix (uniform) structure. It was shown that CS NPs had the most sustained release of the 2 formulations, demonstrating a slower linear release post initial burst and longer duration. The role of particle architecture on the rate of drug release in vitro was confirmed by fitting the experimental data with various kinetic models. This indicated that the release process was a simple diffusion mechanism. The CS NPs were effectively internalized into the endolysosomal compartments of cancer cells and demonstrated an increased cytotoxic efficacy (concentration of a drug that gives half maximal response [EC50] reaching 6.2 mu M) compared to free drug (EC50 = 9 mu M) and uniform CDDP-distributed NPs (EC50 = 7.6 mu M) in vitro. Thus, these experiments indicate that engineering the structure of PLGA NPs can be exploited to control both the dosage and the release characteristics for improved clinical chemotherapy treatment.
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