Intracellularly Biodegradable Polyelectrolyte/Silica Composite Microcapsules as Carriers for Small Molecules

Abstract

Microcapsules that can be efficiently loaded with small molecules and effectively released at the target area through the degradation of the capsule shells hold great potential for treating diseases. Traditional biodegradable polyelectrolyte (PE) capsules can be degraded by cells and eliminated from the body but fail to encapsulate drugs with small molecular weight. Here, we report a poly-l-arginine hydrochloride (PARG)/dextran sulfate sodium salt (DEXS)/silica (SiO2) composite capsule that can be destructed in cells and of which the in situ formed inorganic SiO2 enables loading of small model molecules, Rhodamine B (Rh-B). The composite capsules were fabricated based on the layer-by-layer (LbL) technique and the hydrolysis of tetraethoxysilane (TEOS). Capsules composed of nondegradable PEs and SiO2, polyllamine hydrochloride (PAH)/poly(sodium 4-styrenesulfonate) (PSS)/silica (the control sample), were prepared and briefly compared with the degradable composite capsules. An intracellular degradation study of both types of composite capsules revealed that PARG/DEXS/silica capsules were degraded into fragments and lead to the release of model molecules in a relatively short time (2 h), while the structure of PAH/PSS/silica capsules remained intact even after 3 days incubation with B50 cells. Such results indicated that the polymer components played a significant role in the degradability of the SiO2. Specifically, PAH/PSS scaffolds blocked the degradation of SiO2. For PARG/DEXS/silica capsules, we proposed the effects of both hydrolytic degradation of amorphous silica and enzymatic degradation of PARG/DEXS polymers as a cell degradation mechanism. All the results demonstrated a new type of functional composite microcapsule with low permeability, good biocompatibility, and biodegradability for potential medical applications.

Inorganic/Organic Multilayer Capsule Composition for Improved Functionality and External Triggering

“…[46,47] Substituting the inorganic shell with an inorganic/organic composite significantly increases the functionality of the capsules that can potentially find wide ranging application in medicine. [49][50][51] Application of sol-gel method for functionalization of PE microcapsules has not been reported so far to the best of our knowledge. Most of them have used LbL assembly technique focusing on the basis of the electrostatic interaction among PEs and inorganic silica nanoparticles.…”

“…[50] The biodegradable capsules consisting of poly-L-arginine hydrochloride (PARG)/dextran sulfate sodium salt (DEXS) were coated by silica using sol-gel approach. Very recently, it has been reported new results about biodegradable PE/silica composite microcapsules as carriers for small molecules.…”

“…[50] The biodegradable capsules consisting of poly-L-arginine hydrochloride (PARG)/dextran sulfate sodium salt (DEXS) were coated by silica using sol-gel approach. [50] The principle of cargo release was based on the in vitro hydrolysis of amorphous silica and enzyme-driven decomposition of PARG and DEXS in the presence of cells. According to the CLSM image ( Figure 4G), the high fluorescence intensity of (PARG/DEXS) 4 /silica PE composite capsules can be observed that confirms successful encapsulation of small cargo such as Rh-B.…”

“…Reproduced with permission [50]. G) CLSM image of (PARG/DEXS) 4 /silica composite capsules containing Rh-B.…”

Hybrid inorganic-organic capsules for efficient intracellular delivery of novel siRNAs against influenza A (H1N1) virus infection

“…Nowadays, the use of sol-gel chemistry for the functionalization of PE microcapsules is a particular attractive aspect that could facilitate the development of PE microcapsules in biomedicine. Indeed, the sol-gel chemistry provides excellent opportunity to fabricate hybrid microcapsules with novel physicochemical features, including a low permeability and intracellular degradation 40, 41 . Here, we focus on biodegradable polyelectrolytes and orthosilicate as sol-gel precursor for the formation of SiO 2 shell onto the surface of microcapsule.…”