Tailored intracellular delivery via a crystal phase transition in 400 nm vaterite particles

Abstract

Porous vaterite containers of 400 nm size are studied with respect to intracellular drug delivery applications. A generic crystal phase transition from vaterite to calcite serves as a novel payload release mechanism, which reveals a delayed burst-release. This will permit control of the pharmacokinetics allowing for applications like preventive drug administration or scheduled application of pharmaceuticals during long term therapy. Experiments with two types of payloads, providing different molecular weights and zeta-potentials, demonstrate a flexible way of tailoring the payload delivery time via the molecular properties of the cargo. A dual in vitro cellular uptake experiment with human ovarian carcinoma cells ES2 and human fibroblasts MRC5 shows no cytotoxicity, no influence on cell viability, and fast penetration of substance-loaded containers into cells. Flow cytometry analysis proves high uptake rates and 3D microscopy analysis reveals the intracellular distribution

Diatom-inspired skeletonisation of insulin – Mechanistic insights into crystallisation and extracellular bioactivity

“…To date, insulin has been loaded into manufactured carriers [46,47] by adsorption or co-precipitation methods [48,49,50]. Contrary to this approach, we intend to 'grow' a mineral skeleton-like cage around and between insulin molecules, similar in concept to how a diatom frustule encages an underlying cell.…”

Colloidal micro- and nano-particles as templates for polyelectrolyte multilayer capsules

“…Thus, with pore sizes well above 10 nm, the CaCO 3 particles are not nanoporous, but can be considered mesoporous [51]. In 430 nm vaterite particles, the average pore size is~30 nm [52], in 4 μm-particles it is 35 nm, and 18 μm-particles have a pore size distribution ranging from 20 to 60 nm [51]. Thus, it appears that upon decreasing the size of the particles to less than 4 μm, the pore size reaches an average value of 30-35 nm.…”

“…Thus, it appears that upon decreasing the size of the particles to less than 4 μm, the pore size reaches an average value of 30-35 nm. Biocompatibility tests for vaterite particles indicated no cytotoxicity and no influence on viability or metabolic activity [52].…”

“…In previous work [52], the authors demonstrated the release based on this process and studied it for encapsulated cargo of different sizes: for high molecular weight tetramethyl-rhodamine isothiocyanate TRITCdextran [52], for the low molecular weight model substance Rhodamine 6G [52,66], and for the drug photosensitizer "Photosens" (a mixture of sulfonated aluminum phthalocyanines AlPcSn, with n = 2, 3 or 4) [55]. The size of particles can vary between 400 nm and 4 μm.…”

“…In (a), the carriers are in a pure vaterite phase loaded with Rh6G; (b) shows the calcite phase where the dye was released to the medium apart from residuals attached to the crystal edges; (c) shows dye release curves for the two payloads Rh6G (Rhodamine) and TD4 (TRITC-dextran) measured by spectrofluorometry during the immersion in water and in ethanol. Reproduced from [52] with permission from The Royal Society of Chemistry.…”