systems are outlined, among which PEC hydrogels, PEM films, and PEC
nanoparticles are treated (Sect. 5.2).
5.1 General Aspects on Drug Delivery from Nanoparticles
Before reviewing the pharmacodynamic aspects of drug delivery by PEC particles,
some general aspects on the particle–cell or particle–biofluid interactions will be
addressed. There are numerous reviews on drug-loaded nanoparticle systems in
general and on factors that influence their delivery modalities and performance. The
review of Duncan and Gaspar [105] presents the current state on systems, classes,
scientific research areas, players and opponents, definitions, and terminology in the
field of nanomedicine, whose individual notations and citations would burst the
extent of this chapter. Their review describes a topological and size classification
that includes liposomes (80–200 nm), (gold) nanoparticles (5–50 nm),
nanocapsules (20–1,000 nm), DNA/drug complexes, polymer/drug conjugates
and therapeutics (5–25 nm), polymer/protein conjugates, antibody/drug conjugates,
albumin/drug conjugates, nanosized drug crystals (100–1,000 nm), and block
copolymer micelles (50–200 nm). On the one hand, it is widely accepted that
drug/nanoparticle formulations offer advantages over pure drug formulations,
e.g., prolonged drug circulation time (in blood), biodistribution, specific and selective local targeting (modification with antibodies, folate), controlled cell uptake
(endocytosis), resistance to phagocytosis, passage through tissue interstices, controlled pharmacodynamics (improved drug availability/release), and chemical and
physical drug protection. On the other hand, drug/nanoparticles can have
disadvantages with respect to toxicology, especially when they are administered
systemically in direct contact with blood. Warning examples in this respect are
poly(L-lactic acid) (PLLA) or poly(lactide-glycolide) (PLGA) nanoparticle
formulations using toxic solvents like methylene chloride [5], or nanoparticular
poly(alkylcyanoacrylate) systems bearing toxic degradation products [106].
Recently, the influence of size, shape, and surface chemistry of nanoparticle
systems on drug delivery performance and modalities like blood circulation time,
biodistribution, pharmacokinetics, toxicology, targeting ability, and internalization
have been comprehensively reviewed and outlined by Petros and DeSimone [107].
Nanoparticle uptake by, e.g., internalization in the target cells, is still treated as the
key factor in this and other earlier articles. Important properties and requirements in
this respect were identified and can be summarized by the following four points:
1. Rigid spherical particles of 100–200 nm diameter have the highest potential for
prolonged blood circulation time, biodistribution, and cellular uptake by endocytosis because they are large enough to avoid uptake in the liver, but small
enough to avoid filtration in the spleen and removal by phagocytes, blockage of
blood capillaries, and inflammatory tissue responses [108, 109]. This may also
hold in principle for nonspherical particles by engineering deformability into
234
M. M€ uller
nanoparticles are treated (Sect. 5.2).
5.1 General Aspects on Drug Delivery from Nanoparticles
Before reviewing the pharmacodynamic aspects of drug delivery by PEC particles,
some general aspects on the particle–cell or particle–biofluid interactions will be
addressed. There are numerous reviews on drug-loaded nanoparticle systems in
general and on factors that influence their delivery modalities and performance. The
review of Duncan and Gaspar [105] presents the current state on systems, classes,
scientific research areas, players and opponents, definitions, and terminology in the
field of nanomedicine, whose individual notations and citations would burst the
extent of this chapter. Their review describes a topological and size classification
that includes liposomes (80–200 nm), (gold) nanoparticles (5–50 nm),
nanocapsules (20–1,000 nm), DNA/drug complexes, polymer/drug conjugates
and therapeutics (5–25 nm), polymer/protein conjugates, antibody/drug conjugates,
albumin/drug conjugates, nanosized drug crystals (100–1,000 nm), and block
copolymer micelles (50–200 nm). On the one hand, it is widely accepted that
drug/nanoparticle formulations offer advantages over pure drug formulations,
e.g., prolonged drug circulation time (in blood), biodistribution, specific and selective local targeting (modification with antibodies, folate), controlled cell uptake
(endocytosis), resistance to phagocytosis, passage through tissue interstices, controlled pharmacodynamics (improved drug availability/release), and chemical and
physical drug protection. On the other hand, drug/nanoparticles can have
disadvantages with respect to toxicology, especially when they are administered
systemically in direct contact with blood. Warning examples in this respect are
poly(L-lactic acid) (PLLA) or poly(lactide-glycolide) (PLGA) nanoparticle
formulations using toxic solvents like methylene chloride [5], or nanoparticular
poly(alkylcyanoacrylate) systems bearing toxic degradation products [106].
Recently, the influence of size, shape, and surface chemistry of nanoparticle
systems on drug delivery performance and modalities like blood circulation time,
biodistribution, pharmacokinetics, toxicology, targeting ability, and internalization
have been comprehensively reviewed and outlined by Petros and DeSimone [107].
Nanoparticle uptake by, e.g., internalization in the target cells, is still treated as the
key factor in this and other earlier articles. Important properties and requirements in
this respect were identified and can be summarized by the following four points:
1. Rigid spherical particles of 100–200 nm diameter have the highest potential for
prolonged blood circulation time, biodistribution, and cellular uptake by endocytosis because they are large enough to avoid uptake in the liver, but small
enough to avoid filtration in the spleen and removal by phagocytes, blockage of
blood capillaries, and inflammatory tissue responses [108, 109]. This may also
hold in principle for nonspherical particles by engineering deformability into
234
M. M€ uller