Stable Polymer Nanoparticles with Exceptionally High Drug Loading by Sequential Nanoprecipitation

Abstract

Poor solubility often leads to low drug efficacy. Encapsulation of water‐insoluble drugs in polymeric nanoparticles offers a solution. However, low drug loading remains a critical challenge. Now, a simple and robust sequential nanoprecipitation technology is used to produce stable drug‐core polymer‐shell nanoparticles with high drug loading (up to 58.5 %) from a wide range of polymers and drugs. This technology is based on tuning the precipitation time of drugs and polymers using a solvent system comprising multiple organic solvents, which allows the formation of drug nanoparticles first followed by immediate precipitation of one or two polymers. This technology offers a new strategy to manufacture polymeric nanoparticles with high drug loading having good long‐term stability and programmed release and opens a unique opportunity for drug delivery applications.

Development of High‐Drug‐Loading Nanoparticles

“…Moreover, the shell can be engineered to offer tunable release (e. g., sustained or stimuli‐responsive release), and it can also be modified for various biological applications by conjugating targeting moieties, linkers spacers, or other functional moieties such as drug delivery, biosensing, imaging, diagnostics . Notably, most of the nanoparticle systems using this strategy adopt polymers as their shell material, because of their excellent biocompatibility, biodegradability, and simple fabrication methods . Some other materials silica and lipids have also been attempted.…”

“…Liu et al. developed a drug‐core polymer‐shell nanoparticle with high drug‐loading of 58.5 % by a bulk sequential nanoprecipitation method using various polymers (poly(lactic‐co‐glycolic acid) (PLGA), PLGA‐PEG, PLA‐PEG and shellac) and drugs (PTX, docetaxel, curcumin, ketamine, ibuprofen, amphotericin B, scutellarin and bulleyaconitine A, Figure ) . Different from the microfluidic approach which controls the sequence of introducing non‐solvents to precipitate drug and polymer sequentially, this bulk method was to control the precipitation time of drug and polymer by using a solvent mixture containing multiple solvents.…”

“…The clinical translation of such nanomedicines is challenging due to hurdles like high production cost, problems in scale‐up productions with reproducible properties, and possible toxic side‐effects from the nanomaterials. Furthermore, to achieve a drug therapeutic window, very high particle concentration is required, but the very viscous solution of such high NP concentration leads to difficulties in i. v. injection . Thus, it is critical to increase drug loading thus minimizing these adverse effects .…”

J‐Aggregate‐Based FRET Monitoring of Drug Release from Polymer Nanoparticles with High Drug Loading

“…In our previous work, we reported an ew sequential nanoprecipitation approach to fabricate polymer nanoparticles with exceptionally high drug loading using aw ide range of drugs and polymers. [5,14] Thes equential nanoprecipitation approach is based on tuning the precipitation time of drugs and polymers using am ulti-solvent system, leading to the formation of drug nanoparticles followed by the instant precipitation of ap olymer thus forming drug-core polymershell nanoparticles.T ypically,adrug and ap olymer at a1 :1 weight ratio are first dissolved in as olvent mixture of dimethyl sulfoxide (DMSO), dimethylformamide and ethanol. Phosphate buffered saline buffer at pH 7.4 is poured into this solution with gentle mixing (Figure 1), forming drug-core polymer-shell nanoparticles.I nt he case of using poly (d, llactide-co-glycolide)-block-poly(ethylene glycol) (PLGA 10K -PEG 5K )a st he polymer and curcumin as the drug, curcuminloaded polymeric nanoparticles with 58.5 wt %d rug loading exhibit am ultiple drug-core structure (Figure 1a4).…”

Biomimetic core–shell silica nanoparticles using a dual-functional peptide

“…The choice of material for the core and shell affect greatly their final applications [2]. Depending on the selection of the shell materials, methods for making core-shell nanoparticles are diverse [2,3], such as precipitation [4][5][6], polymerization [7][8][9][10], microemulsion [11][12][13], sol-gel condensation [14,15], and layer by layer adsorption techniques [16,17].…”