Biomedical Engineering Reference
In-Depth Information
continuous technology is a modi
cation of the batch system made by introducing two
in
ow line to keep the
receiving bath volume constant. The anionic solution is again dispersed in the form of a
spray.
These nanoparticles consist of an inner core which holds the desired drug or protein,
and a semi-permeable membrane shell (corona). Both positively and negatively charged
nanoparticles can be produced, depending on the sequence of polymer addition. Various
chemical constituents have been tested, including a combination of at least two anionic
polymers in the droplet-forming phase, and one cationic polymer plus a small inorganic
ion in the corona-forming phase. Components used in the core of the particles include
alginates, gellan gum, sodium cellulose sulphate,
ow lines (anionic and cationic polymer solutions) and one over
-carrageenan, pentasodiumtripoly
(phosphate) and, for the shell chitosan glutamate, poly(methylene-co-guanidine)
hydrochloride and calcium chloride. For loaded samples, the model protein chosen was
ovalbumin, a prototype for vaccine delivery.
In general, such nanoparticles are created using a minimum of two interacting pairs.
The mechanism of particle formation, according to Prokop et al.( 2001 ), is that a core
gelling polysaccharide (or polyanion blend) and a small inorganic ion form the
κ
first pair,
reacting almost instantaneously and providing mechanical stability to the particles, as
well as a template (preformed structure) for the second interacting pair. The second
interaction develops more slowly when polymers (corona, shell) complex via mutual
interpenetration (diffusion) since at least one component of the second pair is of high
molecular mass. Nanostructures result primarily from PECs.
It is likely that thermodynamic rearrangements of the already formed aggregates
proceed over rather longer times, and involve conformational changes, disentanglements
etc., which are a source of complex instability. The corona-forming complex also
provides some degree of permeability control. The corona contains a so-called polox-
amer triblock copolymer type (PEO n -
PEO n ) dissolved into the batch. As the
guest polyanion solution drops into the host polycation solution, cationic particles form
and grow in size. If the particles
PPO m -
charge is neutralized (i.e. at a stoichiometric charge
ratio), aggregation occurs and a bulky precipitate is formed, so useful nanoparticles are
produced before the stoichiometric charge ratio is reached. Surface properties of nano-
particles are therefore charge, porosity, size and degree of hydrophilicity. The poloxamer
type triblock copolymer acts as steric stabilizer, the corona reducing surface adhesion or
interaction with various biological components. The entropic and osmotic barrier over-
comes the protein or particle
'
particle interaction that causes aggregation. The amount of
poloxamer is very low, but suf
-
cient to provide adequate stability and prevent aggrega-
tion during a centrifugation step (Peppas, 1986 ). Encapsulation ef
ciency is de
ned as
the percentage of protein mass recovered, and drug loading is de
ned as the percentage of
protein mass in the total mass of the
final product. Nanoparticles were assessed against
these criteria.
The manner in which the protein is released from the nanoparticles is dependent on the
chemical nature of the nanoparticles. The protein is released by diffusion if its liberation
occurs faster than the degradation of the matrix. Particles also swell according to the
matrix composition (ionizable groups, degree of cross-linking) and environmental
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