3 Sizing of PEC Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
3.1 PEL Structural Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
3.2 Media Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
3.3 Sizing the Internal Structural Density of PECs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
4 Shaping of PEC Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
4.1 Spherical PEC Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
4.2 Rod-like PECs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
4.3 Toroid PEC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
5 Pharmaceutical Applications of PEC Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
5.1 General Aspects on Drug Delivery from Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
5.2 Drug Delivery from PEC Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
5.3 Interaction of PEC Particles with Cells and Biofluids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
6 Summary and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
1 Introduction
Polymer-based nanoparticles are increasingly used for the immobilization, storage,
carriage, and release of drugs and proteins. In this context, the nanodimension
offers a high surface-to-volume ratio and allows interaction with biological systems
at their structural size level. Examples of widely known polymeric nanoparticular
systems for biomedical and pharmaceutical applications are polymer liposomes
[1, 2], block copolymer micelles [3, 4], solid polymer nanoparticles [5, 6], polymer
capsules [7, 8], and spherical PEL brushes [9]. Related to both systems and
applications, the aim of our work is to prepare nanoparticles on the basis of PEL
complexes (PEC) in aqueous media. Generally, PEC are the product of the volume
reaction between a polycation (PC
+
) and its counter anions (CA
À
) and a polyanion
(PA
À ) and its counter cations (CC
+
) according to:
PC
+. . . CA
À + PA
À. . .
CC
+
! PCÀPA + CA
À + CC
+
Three different product types resulting from PEL complexation in the volume
phase are shown in Fig. 1.
Molecular complexes containing few PEL (N ( 10) are formed (clear
solutions) by mixing highly dilute polycation and polyanion solutions. Colloidal
aggregated structures (coacervate phase) containing nanoparticles of many PEL
(N ) 100) are obtained (turbid dispersions) at increased PEL concentrations.
Microscopic to macroscopic precipitate structures are formed by mixing highly
concentrated polycation and polyanion solutions.
Our work is mainly focused on colloidal PEC particles, which are prepared by
mixing polycation and polyanion solutions in nonstoichiometric ratios [10–15], and
on exploring their potential to interact in a useful manner with pharmaceutically
and biomedically relevant compounds. The main issues of our research are reproducibility in the preparation protocol, uniformity of size and shape, conservation of
colloidal stability after binding of compounds and the interaction with surfaces. In
typical PEC systems, standard cationic and anionic PELs and PELs of natural origin
(e.g., polypeptides, polysaccharides, and their modified analogues) are combined.
198
M. M€ uller
3.1 PEL Structural Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
3.2 Media Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
3.3 Sizing the Internal Structural Density of PECs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
4 Shaping of PEC Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
4.1 Spherical PEC Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
4.2 Rod-like PECs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
4.3 Toroid PEC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
5 Pharmaceutical Applications of PEC Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
5.1 General Aspects on Drug Delivery from Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
5.2 Drug Delivery from PEC Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
5.3 Interaction of PEC Particles with Cells and Biofluids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
6 Summary and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
1 Introduction
Polymer-based nanoparticles are increasingly used for the immobilization, storage,
carriage, and release of drugs and proteins. In this context, the nanodimension
offers a high surface-to-volume ratio and allows interaction with biological systems
at their structural size level. Examples of widely known polymeric nanoparticular
systems for biomedical and pharmaceutical applications are polymer liposomes
[1, 2], block copolymer micelles [3, 4], solid polymer nanoparticles [5, 6], polymer
capsules [7, 8], and spherical PEL brushes [9]. Related to both systems and
applications, the aim of our work is to prepare nanoparticles on the basis of PEL
complexes (PEC) in aqueous media. Generally, PEC are the product of the volume
reaction between a polycation (PC
+
) and its counter anions (CA
À
) and a polyanion
(PA
À ) and its counter cations (CC
+
) according to:
PC
+. . . CA
À + PA
À. . .
CC
+
! PCÀPA + CA
À + CC
+
Three different product types resulting from PEL complexation in the volume
phase are shown in Fig. 1.
Molecular complexes containing few PEL (N ( 10) are formed (clear
solutions) by mixing highly dilute polycation and polyanion solutions. Colloidal
aggregated structures (coacervate phase) containing nanoparticles of many PEL
(N ) 100) are obtained (turbid dispersions) at increased PEL concentrations.
Microscopic to macroscopic precipitate structures are formed by mixing highly
concentrated polycation and polyanion solutions.
Our work is mainly focused on colloidal PEC particles, which are prepared by
mixing polycation and polyanion solutions in nonstoichiometric ratios [10–15], and
on exploring their potential to interact in a useful manner with pharmaceutically
and biomedically relevant compounds. The main issues of our research are reproducibility in the preparation protocol, uniformity of size and shape, conservation of
colloidal stability after binding of compounds and the interaction with surfaces. In
typical PEC systems, standard cationic and anionic PELs and PELs of natural origin
(e.g., polypeptides, polysaccharides, and their modified analogues) are combined.
198
M. M€ uller