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Volume 4
Nano Research & Applications
ISSN: 2471-9838
Page 63
JOINT EVENT
August 16-18, 2018 | Dublin, Ireland
&
12
th
Edition of International Conference on
Nanopharmaceutics and Advanced Drug Delivery
25
th
Nano Congress for
Future Advancements
Nano Congress 2018
&
Nano Drug Delivery 2018
August 16-18, 2018
Formulation of peptide and protein therapeutics into nanoparticles by ion pairing for prolonged
activity and improved delivery
Robert K Prud'homme, Kurt D Ristroph
and
Paradorn Rummaneethorn
Princeton University, USA
B
iologics, the fastest-growing sector of the pharmaceutical marketplace, are an attractive class of therapeutics because
of their impressive potency, high selectivity, and reduced off-target effects. But while the effectiveness of these drugs
outclasses many of their small-molecule predecessors, administering biologics remains a challenge. Physiological barriers such
as chemical digestion (when taken orally), rapid blood clearance (when injected), or thick pulmonary mucus (when inhaled)
chemically or physically prevent biologics from reaching their targets and working as designed. To reduce the frequency of
dosing, strategies of protecting these proteins and peptides within delivery vehicles have arisen, but the majority of these
processes suffer from high losses and poor scalability. We here present a scalable and continuous method of encapsulating
water-soluble charged biologics into polymeric nanoparticles. This is done by simultaneously reversibly ionically modifying the
biologics of interest with hydrophobic counterions and controllably precipitating the newly-formed hydrophobic complex into
nanoparticles via the polymer-directed Flash NanoPrecipitation technique. This combined technique, termed hydrophobic
ion pairing Flash NanoPrecipitation (HIP-FNP), is applicable to a wide variety of peptides and proteins, both anionic and
cationic. Importantly, the process is continuous, scalable, and achieves encapsulation efficiencies greater than 95%. We herein
demonstrate encapsulation of two model proteins: the cationic enzyme lysozyme (MW 14,300 D) and the anionic protein
ovalbumin (MW 42,700 D). By altering the identity or amount of hydrophobic counterion used, we can tune protein release
rates, an important consideration for prolonged delivery. Importantly, we also show that the proteins’ activity has been retained
throughout the processing steps. We believe this technique offers a route forward for improving the delivery of many biologic
therapeutics and may improve patient comfort and compliance by simplifying dosing regimens.
Recent Publications
1. Pinkerton N M et al. (2014) gelation chemistries for the encapsulation of nanoparticles in composite gel microparticles
for lung imaging and drug delivery. Biomacromolecules. 15(1):252-261.
2. D’Addio S M et al. (2072) Determining drug release rates of hydrophobic compounds from nanocarriers. Phil. Trans. R.
Soc. A. 374(2072): pii:20150128.
3. D’Addio S M et al. (2013) Optimization of cell receptor-specific targeting through multivalent surface decoration of
polymeric nanocarriers. Journal of Controlled Release. 168(1):41-49.
4. D’Addio S M et al. (2013) Aerosol delivery of nanoparticles in uniformmannitol carriers formulated by ultrasonic spray
freeze drying. Pharmaceutical Research. 30(11):2891-2901.
5. D'addio S M and R K Prud'homme (2011) Controlling drug nanoparticle formation by rapid precipitation. Advanced
Drug Delivery Reviews. 63(6):417-426.
Biography
Robert Prudhomme is a Professor in the Department of Chemical and Biological Engineering at Princeton University, USA. He is the Founding Director of the
Program in Engineering Biology. His research program focusses on polymer self-assembly applied to drug delivery. The development of Flash Nanoprecipitation
(FNP) in his laboratory enabled the encapsulation of poorly soluble drug compounds and oligonucleotides for therapy directed towards cancer, TB, and injections.
FNP is a scalable and continuous process that is enables integrated processing and spray drying for low cost oral and aerosol formulations. Under sponsorship by
the Bill and Melinda Gates Foundation, the process is being adopted to formulate new compounds coming from TBA, MMV, and DNDi.
Prudhomm@princeton.eduRobert K Prud'homme et al., Nano Res Appl 2018, Volume 4
DOI: 10.21767/2471-9838-C3-015