Abstract
AbstractThe self‐assembly of specific polymers into well‐defined nanoparticles (NPs) is of great interest to the pharmaceutical industry as the resultant materials can act as drug delivery vehicles. In this work, a high‐throughput method to screen the ability of polymers to self‐assemble into NPs using a picoliter inkjet printer is presented. By dispensing polymer solutions in dimethyl sulfoxide (DMSO) from the printer into the wells of a 96‐well plate, containing water as an antisolvent, 50 suspensions are screened for nanoparticle formation rapidly using only nanoliters to microliters. A variety of polymer classes are used and in situ characterization of the submicroliter nanosuspensions shows that the particle size distributions match those of nanoparticles made from bulk suspensions. Dispensing organic polymer solutions into well plates via the printer is thus shown to be a reproducible and fast method for screening nanoparticle formation which uses two to three orders of magnitude less material than conventional techniques. Finally, a pilot study for a high‐throughput pipeline of nanoparticle production, physical property characterization, and cytocompatibility demonstrates the feasibility of the printing approach for screening of nanodrug delivery formulations. Nanoparticles are produced in the well plates, characterized for size and evaluated for effects on metabolic activity of lung cancer cells.
Highlights
Over the last few decades, the application of nanotechnologies to the biomedical and pharmaceutical field has significantly enhanced global health, improving diagnosis and treatment of several diseases.[1],[2] A plethora of different materials has been used to produce nanosized carriers, from biodegradable polymers and lipids up to inorganic materials, and to date 51 nanoparticle (NP) formulations have been approved by the FDA for clinical applications (e.g. Neulasta, Copaxone[3])
Different materials have been printed by inkjet systems spanning from cells,[10] to genes[11],[12] or proteins[13] to polymers[14] to nanomaterials and some pharmaceutical formulations.[15],[16],[17] In a singular and pioneering work by Hauschild et al, [15] unilamellar nano-vesicles were printed from a conventional desktop inkjet printer, using ethanol solutions of both lipid-like and amphiphilic copolymers, resulting in NPs with reproducible sizes ranging between 50 and 220 nm
2.1 Validation of the use of ink-jet printing as a miniaturized methodology to screen polymers self-assembling in water by means of traditional analysis. 2.1.1 Known block-copolymer structures Block co-polymers widely used in the drug delivery field such as mPEG-b-PCL and mPEG-bPLGA,[22],[23],[24] well-known to self-assemble in water into NPs, were first used to test the usefulness of the ink-jet printer as a NP formation screening technique. mPEG-b-PCL and mPEG-b-PLGA (50/50) were initially analysed at one single concentration (Figure 1a)
Summary
Over the last few decades, the application of nanotechnologies to the biomedical and pharmaceutical field has significantly enhanced global health, improving diagnosis and treatment of several diseases.[1],[2] A plethora of different materials has been used to produce nanosized carriers, from biodegradable polymers and lipids up to inorganic materials, and to date 51 nanoparticle (NP) formulations have been approved by the FDA for clinical applications (e.g. Neulasta, Copaxone[3]). All the concentrations were chosen based on previously published methods shown to allow polymer chains to self-assemble in water, and the data for these polymers were compared against appropriate control materials.[18],[19] The versatility of the ink-jet printing technology presented here as a miniaturized screening method may have implications for multiple pharmaceutics platforms In this regards, Giardiello et al.[20] developed an accelerated nanomedicine platform to generate a potential aqueous paediatric HIV nanotherapy, targeting oral dose, with clinical translation and regulatory approval for human evaluation. The inkjet NP-fabrication method of the present work might be employed as a miniaturized pre-formulation screening step to be integrated within the work of Giardiello reported above or within general accelerated nanomedicine platform approaches where nanodispersions are screened as a valuable alternative to molecular solutions.[21] as a case study for a high throughput pipeline for nanoparticle production, characterization and effects on cell metabolic activity, a small experiment with selected polymers was performed. This proof-of-concept ‘on-line assay’ demonstrated the feasibility of the printing approach to screen formulations, from nano-particle preparation to preliminary cytotoxicity assays in a high-throughput fashion
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