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Nanocapsules for Targeted Controlled Delivery of Chemicals

Final Report Summary - NANOCAPS (Nanocapsules for Targeted Controlled Delivery of Chemicals)

During the 'Nanocapsules for targeted controlled delivery of chemicals' (Nanocaps) project period from month 1 to month 36, the following materials were produced.

- New types of nanoparticles (to be applied as core vectors for active molecules) have been prepared. These include nanoparticles containing naphthylacetic acid for anti-proliferating application, a series of acrylic monodisperse nanoparticle dispersions produced by freeradical polymerisation, and polymer / silica composite nanoparticles for metal plating application.

- Nanosized emulsions for anti-proliferating application have been prepared by membrane emulsification. The size of chloroform / water emulsion droplets was as low as 44 nm. Flurorinated oil emulsions in water were prepared with a size of ca. 200 nm and a polydispersity index of 0.8. New ceramic membranes have been produced with better homogeneity and surface quality. Monodisperse emulsion droplets could be prepared with surface modified membranes in order to reduce the porosity.

- Nanosized gel complex particles for multiple applications have been prepared by membrane emulsification. The smallest size is 80 nm. The stability needs to be improved. For anti-proliferating application, nano-engineered shells made by LbL on nano-emulsion containing a model drug molecule were produced. About 10 % of drug molecule was quickly released in the aqueous phase.

- Microcapsules for anti-proliferating application were prepared by LbL on chloroform / water emulsions from membrane emulsification. Polyelectrolyte capsules with embedded drugs were prepared from porous calcium carbonate. Encapsulation efficiency was found to be 40 and 21 % for a water insoluble dye and a water soluble drug, respectively. For metal plating application, several formulations that are potential candidates as active components for encapsulation have been tested and one formulation showed very promising anti-corrosion properties on steel.

- Theoretical model of capsules, capsules interactions and capsules-surface interactions were formulated based on the combination of DLVO, hydrodynamic forces and steric interactions. For anti-allergic application, two types of capsules were focused on one with fast release to obtain immediate effect and the other with slow release for longer term effect (up to 6 months). Different shell materials have been tried out and the best candidates were identified. Capsules stable up to 90 days under in-vitro conditions could be prepared.

For metal plating application, stable hollow capsules were made using PSS / PDADMAC as a shell by LbL deposition. PSS and PDADMAC are promising materials that can withstand plating solution compositions. A fluorescent substance was encapsulated to follow the release properties. Immediate deformation was observed in the plating solution. After one hour in the alkaline plating solution all of the fluorescent material was released. Microcapsules were prepared from coacervation of PAH / PSS complex on CaCO3 cores. The understanding of the mechanism of layer deposition of the shell was greatly improved with synthetic polyelectrolytes, poly(allylamine, HCl)-poly(styrene sulfonate) and on natural polymers: chitosan and alginate. New homopolymers of MADQUAT and copolymers of acrylic acid- MADQUAT aiming to be applied instead of the natural chitosan have been synthesized.

- Nanodiamonds, nanoalumina and nano-SiC particles have been successfully produced and the scale-up was realised. Nanodiamonds and nanoalumina particles were coated for metal plating application. The alumina particles produced can be used for membrane preparation.

- Hollow micro- and nanocapsules were prepared for metal plating application. The in-situ formation of the silica shell has been studied.

LbL growth mechanism was explained with help of advanced characterisation methods (reflectometry, streaming potential, imaging ellipsometry, microelectrophoresis), and equipment constructed and developed. Laser reflectometry provided a sensitive way to measure polymer adsorption on surfaces and permitted the determination of in-situ adsorption and desorption processes, to adsorption rate and possible polymers rearrangement in the shell.

The transfer of active molecules through capsule shells was characterised by permeability measurements using electrochemical techniques and fluorimetry and fluorescent microscopy.

The permeability of PAH/PSS shells is lower than alginate / chitosan. Release of small molecules (fluorescein) through capsule shells of five polyelectrolyte bilayer is retarded 100 times with respect to bare dye particle. Temperature and pH of the solution may be used to control the transfer of small molecules through shells. Both factors may affect the stability of the shell layers as well.

- New capsules with thermo-sensitive and pH-responsive properties were prepared and used to encapsulate model polymers. The encapsulation and release mechanisms were studied.

A novel method for remote release of encapsulated polymers using laser light illumination was developed. The release of a fluorescently labelled polymer from a polyelectrolyte multiplayer capsule was observed for the first time. The composition of the shell was defined.

Methods of time dependent streaming potential and dynamic contact angle, imaging single wave ellipsometry were developed, extended and applied for studying mono and multilayer polyelectrolyte systems. The methods were implemented to perform the analysis of interfacial properties and stability of polyelectrolyte films.

A new optical impinging cell was developed to study capsule attachment and detachment or code position for metal plating – allowing in-situ observation of microcapsules deposition or fluorescently labelled nanocapsules at non-transparent surfaces. For anti-proliferating application, a high affinity of model capsules to the surface of surgical steel was observed. For anti-proliferating application, adhesion tests of capsules on surgery steel have started.

The feasibility of observing nanocapsules and multilayer films by several near field techniques: AFM (air and liquid), R-SNOM, STOM and transmission fluorescence near field microscopy (emitting probe) was tested. A transmission fluorescence microscope is now fully operational.

For anti-proliferating application:

- Biodegradable nanoparticles containing a model drug and real drug with sizes in the range of 200-350 nm were synthesised. homopolymers of styrene sulfonate and of MADQUAT have been applied in the preparation of various types of nanosized capsules (97-350 nm) and with various zeta potential (- 40 mV to + 50 mV) by a membrane process, plus Fluorescein and Red 8 dyes could be encapsulated and released at high temperature.
- A copolymer that precipitates at low pH was synthesised and applied to prepare capsules containing fluorescein with a mean size of 260 nm by a membrane process. Fluorescein could be released at high pH. a copolymer that forms spontaneously micelles in presence of water was synthesised and applied to encapsulate drug. The capsule size was 40 nm. Chloroform / APS miniemulsions and microemulsion stabilised by surfactants with an average droplet size 40 nm were prepared.
- Drug encapsulated nanoparticles (248 nm) were prepared with a loading of 10 % compared to the dry mass. In-vitro tests were performed to prove the cytotoxicity of drug loaded capsules coated on metallic model surfaces. The cell multiplication was reduced by a factor of 100 after 6 days. Consequently, production and marketing of new capsules coated stents have been initiated.
- For both anti-proliferating application and metal plating application, new types of homopolymers of styrene sulfonate with various polydispersity indexes and copolymers were designed and synthesised. Also, the composition of chloroform / water emulsions prepared by membrane emulsification was optimised as well as the conditions to form a shell layer around the emulsion droplets. The conditions to form PE multilayer shells using various combinations of strong and weak polyelectrolyte layers by spraying were optimised.
- Nanosized capsules (200 nm and 500 nm) made of latex core coated by 11 PE bilayers could be successfully deposited on stainless steel.

For metal plating applications

Silica and functional silica hollow capsules (250 nm) have been prepared by membrane emulsification. The formation of the shell layer has greatly progressed with help of NMR techniques. Composite nanoparticles with an average diameter of 110 nm and a solid content of around 40 wt% were prepared by emulsifier-free emulsion copolymerisation. The produced particles were successfully synthesised on a larger scale (1 litre). Functionalised polymer nanoparticles were found to be compatible in acid plating bath composite nanoparticles were successfully co-deposited with zinc on steel. A promising protecting effect is observed in salt spray test after temperature treatment to 200 degrees Celsius for 1 hour.

Composite nanoparticles were applied as organo-mineral formulations after Cr(III) passivation on galvanised steel and tested in salt spray test for 450 hours. Promising results are observed compared with a standard organo-mineral formulation.

Composite nanoparticles were applied as organo-mineral formulations after Cr(III) passivation on galvanised steel and tested in salt spray test for 450 hours. Promising results are observed compared with a standard organo-mineral formulation. The conditions of shell formation by coacervation of polyelectrolytes on nanosized silica particles have been further studied.

For both anti-proliferating application and metal plating application, new types of homopolymers of styrene sulfonate with various polydispersity indexes and copolymers were designed and synthesised. Also, the composition of chloroform / water emulsions prepared by membrane emulsification was optimised as well as the conditions to form a shell layer around the emulsion droplets.

In addition, 84 publications have been published in international scientific journals with referees and international conferences.