Tatsiana Shutava

Layer-by-Layer-Coated Gelatin Nanoparticles as a Vehicle for Delivery of Natural Polyphenols

Natural polyphenols with previously demonstrated anticancer potential, epigallocatechin gallate (EGCG), tannic acid, curcumin, and theaflavin, were encased into gelatin-based 200 nm nanoparticles consisting of a soft gel-like interior with or without a surrounding LbL shell of polyelectrolytes (polystyrene sulfonate/polyallylamine hydrochloride, polyglutamic acid/poly-l-lysine, dextran sulfate/protamine sulfate, carboxymethyl cellulose/gelatin, type A) assembled using the layer-by-layer technique. The characteristics of polyphenol loading and factors affecting their release from the nanocapsules were investigated. Nanoparticle-encapsulated EGCG retained its biological activity and blocked hepatocyte growth factor (HGF)-induced intracellular signaling in the breast cancer cell line MBA-MD-231 as potently as free EGCG.

Architectural layer-by-layer assembly of drug nanocapsules with PEGylated polyelectrolytes

150-200 nm diameter capsules containing 60-70 wt % of poorly soluble drugs, paclitaxel and camptothecin, were produced by layer-by-layer (LbL) assembly on drug nanocores in a solution containing uncharged stabilizers. Optimization of capsule shell architecture and thickness allowed for concentrated (3-5 mg/mL) colloids that are stable in isotonic salt buffers. Nanoparticle aggregation during the washless LbL-assembly was prevented by using low molecular weight block-copolymers of poly(amino acids) (poly-L-lysine and poly-L-glutamic acid) with polyethylene glycol (PEG) in combination with heparin and bovine serum albumin at every bilayer building step. Minimal amounts of the polyelectrolytes were used to recharge the surface of nanoparticles in this non-washing LbL process. Such PEGylated shells resulted in drug nanocapsules with high colloidal stability in PBS buffer and increased protein adhesion resistance. The washless LbL polyelectrolyte nanocapsule assembly process, colloidal stability and nanoparticle morphology were monitored by dynamic light scattering and electrophoretic mobility measurements, UV-vis spectroscopy, TEM, SEM and laser confocal microscopy imaging.

Layer-by-layer nanoencapsulation of camptothecin with improved activity

160 nm nanocapsules containing up to 60% of camptothecin in the core and 7-8 polyelectrolyte bilayers in the shell were produced by washless layer-by-layer assembly of heparin and block-copolymer of poly-l-lysine and polyethylene glycol. The outer surface of the nanocapsules was additionally modified with polyethylene glycol of 5 kDa or 20 kDa molecular weight to attain protein resistant properties, colloidal stability in serum and prolonged release of the drug from the capsules. An advantage of the LbL coated capsules is the preservation of camptothecin lactone form with the shell assembly starting at acidic pH and improved chemical stability of encapsulated drug at neutral and basic pH, especially in the presence of albumin that makes such formulation more active than free camptothecin. LbL nanocapsules preserve the camptothecin lactone form at pH 7.4 resulting in triple activity of the drug toward CRL2303 glioblastoma cell.

Lipid modified polyelectrolyte microcapsules with controlled diffusion

The lipid coating introduced directly on (polystyrene sulfonate/polyallylamine hydrochloride)5 polyelectrolyte microcapsule surfaces significantly reduces the permeability of capsule walls estimated by fluorescence recovery after photobleaching (FRAP).

Encapsulation of Natural Polyphenols with Antioxidant Properties in Polyelectrolyte Capsules and Nanoparticles

The chapter summarizes approaches to encase natural polyphenols with previously demonstrated anti-cancer potential, curcumin, (-)-epigallocatechin gallate, tannic acid, theaflavin, thearubigin, curcumin, etc. in polyelectrolyte microcapsules and nano/microparticles in order to modulate their biological activity, bioavailability and stability as an alternative to usage of free compounds. Taking into account the matrix-encapsulate interaction, the emphasis is made to the techniques based on reversible complex electrostatic interaction and hydrogen bonding of polyphenols with polymeric matrixes, stability and properties of the obtained microstructures as delivery vehicles, characteristics of polyphenol loading, and factors affecting their release from the nanocapsules. The controversies in manifesting biological and antioxidant activity by polyphenols encased in the aforementioned structures are discussed.

Layer-by-Layer Engineered Microreactors for Bio-Polymerization of 4-(2-aminoethyl) phenol hydrochloride

This study presents the results of polymerization of phenol to yield fluorescent polymer encapsulated within shells fabricated via layer-by-layer (L-b-L) assembly. Hollow polyelectrolyte microcapsules (shells) were prepared using weakly cross-linked melamine formaldehyde (MF) particles. Dissolution of the MF cores was achieved by changing the pH of the solution. Horseradish peroxidase (HRP), the catalyzing enzyme, was loaded in these capsules by taking advantage of the “open/close” mechanism of the capsules by altering the pH. The empty shells were then suspended in a concentrated solution of monomer. Since the monomer is a low molecular weight species, it freely permeates through the polyion wall into the shells. Addition of aliquots of hydrogen peroxide initiated the polymerization reaction and the polymer formed from the ensuing reaction was confined in the shells due to its high molecular weight. The model used for demonstrating this synthesis is polymerization of 4-(2-aminoethyl) phenol hydrochloride commonly known as tyramine hydrochloride to its corresponding polymeric form by reacting it with hydrogen peroxide. Fluorescence spectrometry (FS), confocal laser scanning microscopy (CLSM), and atomic force microscopy (AFM) were the characterization methods employed to confirm polymerization in situ shells.