Abstract:
Targeted delivery of potent, toxic chemotherapy drugs, such as cisplatin, is a significant area of research in cancer treatment. In this study, cisplatin was successfully encapsulated with high efficiency (> 70%) in poly (lactic-co-glycolic acid) polymeric nanoparticles by using electrohydrodynamic atomization (EHDA) where applied voltage and solution flow rate as well as the concentration of cisplatin and polymer were varied to control the size of the particles. Thus, nanoparticles were produced with three different drug:polymer ratios (2.5, 5 and 10 wt% cisplatin). It was shown that smaller nanoparticles were produced with 10 wt% cisplatin. Furthermore, these demonstrated the best sustained release (smallest burst release). By fitting the experimental data with various kinetic models it was concluded that the release is dependent upon the particle morphology and the drug concentration. Thus, these particles have significant potential for cisplatin delivery with controlled dosage and release period that are crucial chemotherapy parameters.
Key words
Cisplatin delivery; Cancer chemotherapy; Nanoparticle; Electrohydrodynamic atomization; Controlled release
Methods
Materials
PLGA (copolymer 50:50, Resomer RG503H, molecular weight of 33,000 Da, inherent viscosity 0.41 dl g− 1) was supplied from Boehringer Ingelheim (Ingelheim, Germany). Dimethylacetamide (DMAc) was obtained from Sigma Aldrich (Poole, UK). Cisplatin (cis-Platinum(ll)diamine dichloride, molecular weight of 300 g mol− 1) was purchased from Enzo Life Sciences (Exeter, UK).
Results
EHDA of cisplatin dissolved in PLGA solution
In EHDA, the flow of liquid under the influence of an electric field undergoes different modes. This is a function of the operating parameters, primarily: the applied electrical potential difference (voltage), the distance between the needle outlet and the ground electrode as well as the liquid flow rate, needle diameter and the properties of the flowing liquid.23 At a constant liquid flow rate and with no electrical field voltage, liquid droplets will form at the tip of the needle and detach once they reach a certain volume. Applying a relatively small electrical potential difference will reduce the diameter of the liquid droplets formed at the tip of the needle but dripping will continue. As the applied voltage is increased however, the atomization mode changes from dripping to jetting.24 The stable cone jet mode is normally the most desirable atomization mode as it can produce uniform size particles (Figure A1 in supporting information). When the applied voltage is slightly higher or lower than that when a single permanent cone jet is emitted from the needle tip, the cone jet pulsates.25 While the pulsated cone jet emits at perfectly timed intervals, the diameter of the cone jet varies and as a result droplets with different diameters are formed leading to generation of polydispersed particles (video camera images and corresponding SEM images are provided in supplementary information).
Citation: Maryam Parhizkar, Philip J.T. Reardon, Jonathan C. Knowles, Richard J. Browning, Eleanor Stride, Pedley R. Barbara, Anthony H. Harker, Mohan Edirisinghe Electrohydrodynamic encapsulation of cisplatin in poly (lactic-co-glycolic acid) nanoparticles for controlled drug delivery doi:10.1016/j.nano.2016.05.005
Received: 31 March 2016, Accepted: 5 May 2016, Available online: 13 May 2016
Coyright: © 2016 he Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (
http://creativecommons.o rg/licenses/by/4.0/).
Acknowledgements
Data supporting this study are provided in the paper and as supplementary information accompanying this paper.
