Freeze drying of polyelectrolyte complex nanoparticles: Effect of nanoparticle composition and cryoprotectant selection

Abstract

This work investigates the impact of nanoparticle (NP) composition and effectiveness of cryo-/lyo-protectants in a freeze drying process, which was employed to convert liquid dispersions of polyelectrolyte complex (PEC) NPs into completely redispersible powders. PEC NPs, with and without peptide, were produced by complex coacervation. The cryo-/lyo-protectants investigated were mannitol, trehalose (TRE) and poly(ethylene glycol) (PEG). The solid state of lyophilised powders was studied by thermal analysis and X-ray diffraction. Cytotoxicity studies were done by MTS assay and flow cytometry. The presence of a cryoprotectant was essential to achieve a successful powder reconstitution. The concentration of TRE was optimised for each type of PEC NPs. Protamine- and hyaluronate-based NPs reconstituted better than chitosan- and chondroitin sulphate-based NPs, respectively. PEG polymers were found to be more effective cryoprotectants than TRE and best results were achieved using co-freeze drying of NPs with TRE and PEG. These ternary NPs/TRE/PEG samples were crystalline, with expected better storage stability. PEG polymers were well tolerated by Caco-2 cells, with the exception of linear PEG 10 kDa. This work shows that, as regards the formulation design and maximising NP loading in the dried product, optimisation of the cryoprotectant type and content is needed as it is highly dependent not only on the type of polyelectrolyte pair in the PEC, but also the polyions ratio.

Optimisation of the self-assembly process: production of stable, alginate-based polyelectrolyte nanocomplexes with protamine

“…It was suggested that, while all the carrageenans studied are able to form polyelectrolyte complexes with PROT, the mechanism of complexation was different for iota carrageenan (Dul et al 2015). Additionally, another reports show a large shift in the amide I band of chitosan, observed after its complexation with HA (Umerska et al 2012), chondroitin sulphate (Umerska et al, 2015) and after complexation of chitosan with kappa carrageenan (Li et al 2013). Therefore, it appears that AAL is another polyanion that has an ability to bind to PROT via electrostatic interactions.…”

“…No considerable difference in the colloidal stability of anionic NPs was observed in the acetate, HEPES and diluted PBS media, even though the concentration of the PBS solution was over a 6-fold lower (0.1M versus 0.015M) than the other two solutions. This might be contributed to the more kosmotropic (order inducing) character of the acetate and 4-(2-hydroxyethyl)-1-piperazineethanesulphonate (HEPES) anions, while the chloride anion is considered more chaotropic (order disrupting) (Umerska et al 2015). Thus lower concentrations of the chloride anions are needed to induce physical instability of NP dispersions.…”

“…The release of the cargo from those NPs was ∼70-80% after 24h (Umerska et al 2014). The release of sCT from chondroitin sulphate/PROT NPs, on the other hand, was susceptible to the pH and ionic strength of release medium (Umerska et al 2015). Wernig et al (2008) studied encapsulation of vasoactive intestinal peptide into biodegradable PROT 18mer nonsense oligonucleotides formed by self-assembly of the components.…”

An overview of lyophilization: troubleshooting the challenges and pharmaceutical applications

“…Particle size reduction increases surface free energy which result in aggregation and destabilization of nanoparticals in suspension. Aggregation/fusion, sedimentation or creaming, crystal growth, change in crystal state are the major reason behind instability of nanoparticle in aqueous solvent [41]. Hence, to improve the long term stability of nanoparticles, colloidal suspension is converted into dry powder form using lyophilization.…”

Carbohydrate-based Trojan microparticles as carriers for pulmonary delivery of lipid nanocapsules using dry powder inhalation

“…Current dry powder inhalers on the market have FPFs ranging between 10 and 70% [23]. Moreover, small size of NPs can lead to particle aggregation due to high surface energy thereby making handling of the NPs in dry powder form very difficult [2,24,25]. Therefore, the major challenge for pulmonary delivery of NPs is to find a proper carrier system with an MMAD suitable for pulmonary delivery [2,26].…”