Speaker
Description
Delivery of drugs to the central nervous system is hindered by low permeability and efflux activity of the blood-brain-barrier (BBB). Encapsulation of drugs in molecularly targeted nanoparticles (NPs) has been widely studied as a means to improve drug penetration into the brain [1]. For example, incorporation of BBB-homing or tumor-penetrating peptides in NPs can significantly enhance drug delivery to brain tumors, such as glioblastoma [2].
Biodegradable polyesters and their copolymers with poly(ethylene oxide) have been widely studied as materials for preparing drug delivery systems and several systems have already advanced to the clinic. However, limited batch-to-batch reproducibility has been identified as an important obstacle in the clinical translation of nanomedicines, and advanced manufacturing techniques based on microfluidics can overcome some of these hurdles [3].
Here, we have developed a nanoparticle platform based on poly(ethylene oxide)-block-polycaprolactone (PEO-b-PCL) for the delivery of hydrophobic drugs to glioblastoma. The particles were manufactured by a nanoprecipitation method under mild conditions using a next generation glass capillary microfluidic technique. Drug loading up to 10 % was achieved and reproducibility of drug loading was improved in comparison to the corresponding bulk method. Precise control over the nanoparticle size was achieved, down to 60 nm in hydrodynamic diameter.
Preliminary in vitro characterization of drug-free NPs suggested a good cytocompatibility. Further in vitro experiments are performed on drug-loaded peptide-decorated NPs to determine drug release behavior, toxicity toward U87 glioblastoma cells, cellular uptake, intracellular fate and long-term stability of the formulation.
[1] Jena et al. Drug Deliv. and Transl. Res. 10 (2019) 304-318.
[2] Ruoslahti, E. Adv. Drug Deliv. Rev. 110-111 (2017) 3-12.
[3] Valencia et al. Nat. Nanotechnol. 7(10) (2012) 623-629.
The project is sponsored by Bayer Oy, Finland.
| Speaker Country | Finland |
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