Mateescu / Ispas-Szabo / Assaad Controlled Drug Delivery

The Role of Self-Assembling Multi-Task Excipients
1. Auflage 2014
ISBN: 978-1-908818-67-6
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band 0, 250 Seiten

Reihe: Woodhead Publishing Series in Biomedicine

In complex macromolecules, minor modifications can generate major changes, due to self-assembling capacities of macromolecular or supramolecular networks. Controlled Drug Delivery highlights how the multifunctionality of several materials can be achieved and valorized for pharmaceutical and biopharmaceutical applications. Topics covered in this comprehensive book include: the concept of self-assembling; starch and derivatives as pharmaceutical excipients; and chitosan and derivatives as biomaterials and as pharmaceutical excipients. Later chapters discuss polyelectrolyte complexes as excipients for oral administration; and natural semi-synthetic and synthetic materials. Closing chapters cover protein-protein associative interactions and their involvement in bioformulations; self-assembling materials, implants and xenografts; and provide conclusions and perspectives. - Offers novel perspectives of a new concept: how minor alterations can induce major self-stabilization by cumulative forces exerted at short and long distances - Gives guidance on how to approach modifications of biopolymers for drug delivery systems and materials for implants - Describes structure-properties relationships in proposed excipients, drug delivery systems and biomedical materials

Mircea Alexandru Mateescu is Professor of Biochemistry, Université du Québec à Montréal, Canada, and is a scientist with expertise in drug delivery systems and biochemical pharmacology. He is inventor of several novel biomaterials with particular characteristics related to supramolecular self-assembling phenomena and promoter of new technologies in pharmaceutical formulations. With more than 125 articles published in refereed specialty journals and 27 Patents, he is leading a large laboratory team. Mateescu is the holder of the J-A. Bombardier ACFAS Prize for Technological Innovation in Canada.

Autoren/Hrsg.

Mateescu, M A

Ispas-Szabo, P.

Assaad, E.

Inhaltsverzeichnis

1;Front Cover;1
2;Controlled Drug Delivery;4
3;Copyright Page;5
4;Contents;6
5;List of figures;8
6;List of tables;16
7;Biography for book;18
8;1 The concept of self-assembling and the interactions involved;20
8.1;1.1 The concept of self-assembling;20
8.1.1;1.1.1 The concept of self-assembling by association/interaction processes;21
8.2;1.2 The nature of forces and types of interactions involved in self-assembly of macromolecules;21
8.3;1.3 Hydrogels and their role in drug conception and development;24
8.3.1;1.3.1 Organogels and micelles for drug delivery;26
8.4;1.4 Self-assembling phenomena in solid dosage forms;26
8.4.1;1.4.1 Hydrogen association and flexibility of chains;26
8.4.2;1.4.2 Ionically stabilized excipients;29
8.4.2.1;1.4.2.1 Two-speed self-assembled monolithic devices;29
8.4.3;1.4.3 Hydrophobic stabilization of excipients and drug release mechanisms;30
8.4.3.1;1.4.3.1 The concept of self-assembling by inclusion processes;33
8.4.3.2;1.4.3.2 Inclusion complexes of starch with fatty bioactive agents;33
8.4.3.3;1.4.3.3 Inclusion complexes and hydrophobic assembly of starch excipients;34
8.5;1.5 Conclusions;36
8.6;References;36
9;2 Starch and derivatives as pharmaceutical excipients;40
9.1;2.1 General aspects;40
9.2;2.2 Structural considerations;41
9.3;2.3 Self-assembling in physically modified starches;50
9.3.1;2.3.1 Pregelatinized starch;50
9.3.2;2.3.2 Multifunctional excipient: binder–filler and binder–disintegrant;52
9.3.3;2.3.3 Extruded starch;52
9.3.4;2.3.4 Soft starch capsules;53
9.3.5;2.3.5 Hard capsules;54
9.3.6;2.3.6 Starch films as functional coatings;56
9.3.7;2.3.7 Starch microspheres and nanospheres in drug delivery;57
9.3.8;2.3.8 Starch complexes;58
9.3.9;2.3.9 Conclusions;67
9.4;2.4 Chemically modified starches and their self-assembling;69
9.4.1;2.4.1 Self-assembling in cross-linked starches;69
9.4.2;2.4.2 Starch ethers;78
9.4.3;2.4.3 Ionic starches and their self-assembling features;81
9.4.3.1;2.4.3.1 CMS as pH-responsive excipient;82
9.4.3.2;2.4.3.2 Cationic starch;91
9.4.4;2.4.4 Conclusions;91
9.5;References;92
10;3 Chitosan and its derivatives as self-assembled systems for drug delivery;104
10.1;Abbreviations;104
10.2;3.1 Introduction;105
10.3;3.2 Unmodified chitosan—self-assembled thermogels;106
10.3.1;3.2.1 Mechanism of chitosan thermogelation;106
10.3.2;3.2.2 Chitosan thermogels;107
10.4;3.3 Amphiphilic chitosan derivatives;109
10.4.1;3.3.1 Alkylated chitosan;109
10.4.2;3.3.2 Acylated chitosan;112
10.4.2.1;3.3.2.1 Acylated chitosan;112
10.4.2.2;3.3.2.2 Acylated chitosan oligosaccharides;113
10.4.3;3.3.3 Cholesterol-modified chitosan;114
10.4.4;3.3.4 Cholic and deoxycholic acid-modified chitosan;116
10.4.5;3.3.5 5ß-Cholanic acid-modified chitosan;119
10.4.6;3.3.6 Phthaloylchitosan and other hydrophobically modified chitosans;122
10.4.7;3.3.7 Hydrophobic drug-grafted chitosan;125
10.5;3.4 Amphiphilic/amphoteric chitosan derivatives;129
10.5.1;3.4.1 Hydrophobically modified carboxylated chitosan;129
10.5.1.1;3.4.1.1 Alkyl-modified carboxylated chitosan;129
10.5.1.2;3.4.1.2 Acyl-modified carboxylated chitosan;131
10.5.1.3;3.4.1.3 Cholesterol-modified carboxylated chitosan;134
10.5.1.4;3.4.1.4 Deoxycholic acid-modified carboxylated chitosan;134
10.5.2;3.4.2 Hydrophobically modified sulfated chitosan;135
10.6;3.5 Conclusion;137
10.7;References;138
11;4 Chitosan-based polyelectrolyte complexes as pharmaceutical excipients;146
11.1;Abbreviations;146
11.2;4.1 Introduction to chitosan-based polyelectrolyte complexes;147
11.2.1;4.1.1 Overview of chitosan-based polyelectrolyte complexes;147
11.2.2;4.1.2 Chitosan-based PECs in drug delivery;148
11.3;4.2 Chitosan–chondroitin sulfate PEC;149
11.4;4.3 Chitosan–carboxymethyl starch PEC;152
11.5;4.4 Chitosan–dextran sulfate PEC;153
11.6;4.5 Chitosan–pectin PEC;157
11.7;4.6 Chitosan–alginate PEC;159
11.7.1;4.6.1 Formulation of active agents with chitosan–alginate PEC;160
11.7.2;4.6.2 Chitosan–alginate beads;161
11.7.2.1;4.6.2.1 Small molecules;162
11.7.2.2;4.6.2.2 Proteins;163
11.7.2.3;4.6.2.3 Other active agents;164
11.7.3;4.6.3 Chitosan–alginate microspheres;164
11.7.4;4.6.4 Chitosan–alginate microcapsules;166
11.7.4.1;4.6.4.1 Small molecules;167
11.7.4.2;4.6.4.2 Proteins;168
11.7.5;4.6.5 Chitosan–alginate microparticles;169
11.7.6;4.6.6 Chitosan–alginate nanoparticles and other forms;171
11.8;4.7 Chitosan complexed with other polysaccharides;172
11.9;4.8 Conclusion;174
11.10;References;175
12;5 Self-assembling in natural, synthetic, and hybrid materials with applications in controlled drug delivery;182
12.1;5.1 General considerations;182
12.2;5.2 Natural polysaccharides and their derivatives used in controlled drug release;189
12.3;5.3 Self-assembling of synthetic polymers;206
12.3.1;5.3.1 Block copolymers as multitasking excipients for biomedical applications;206
12.3.1.1;5.3.1.1 Hydrogels;206
12.3.1.2;5.3.1.2 Thermoresponsive gels;208
12.3.1.3;5.3.1.3 Nanogels;212
12.3.1.4;5.3.1.4 Nanoparticles;213
12.3.1.5;5.3.1.5 Liposomes;215
12.3.2;5.3.2 Layer-by-layer self-assembled structures for drug delivery;218
12.4;5.4 Hybrid materials obtained by self-assembling;221
12.5;5.5 Conclusions;226
12.6;References;227
13;6 Protein–protein associative interactions and their involvement in bioformulations;244
13.1;6.1 Introduction;244
13.2;6.2 Generalities on proteins, their roles, and their possible use as excipients;245
13.3;6.3 Albumin microspheres and nanoparticles for drug delivery;246
13.4;6.4 Self-assembling processes involving albumin and bioactive agents;247
13.5;6.5 Collagen: generalities and utilizations as material for biopharmaceutical applications;248
13.5.1;6.5.1 The collagen structure;248
13.5.1.1;6.5.1.1 Collagen cross-linking;250
13.5.2;6.5.2 Collagen-based biomaterials;250
13.5.3;6.5.3 CPMs and recognition self-assembling;252
13.6;6.6 Protein excipients for solid dosage forms;252
13.7;6.7 Pharmaceutical solid, oral, high-loaded, and gastro-resistant dosage forms of therapeutic enzymes;254
13.8;6.8 Gastro-resistant excipient-free pharmaceutical forms of therapeutic enzymes;255
13.9;6.9 Conclusion;256
13.10;References;257
14;Index;262

Leseproben

1 The concept of self-assembling and the interactions involved
Self-assembling can be defined as the capacity of certain molecules, macromolecules, or composite materials to associate themselves and to form complexes and/or networks or other structures with novel properties. Some of these are particularly useful in technological and biomedical applications. General aspects of forces involved in self-assembling will be discussed for various materials generating excipients such as carbohyddrates, proteins and other materials generating excipients (polylactides-glycolic, polyvinylalcohol, polyurethans, polyacrylates). Assembling forces involved in stabilization of various polymeric excipients are discussed explaining how minor alterations in macromolecular structures (i.e. limited variation of the cross-linking degree of starch, from low to moderate) can generate huge differences in delivery patterns of the drug formulations (ex CL-Starch-6 affording sustained release and CL-Starch-20 acting as a binder and disintegrant). Furthermore, delivery properties are presented in function of the type of assembling characteristics, ex chitosan stabilized by hydrogen association versus hydrophobic self-assembly, ionical materials involved in polyelectrolyte complexation, inclusion complexes. Keywords
self-assembling; drug delivery; bond; energy Chapter Outline 1.1 The concept of self-assembling 1 1.1.1 The concept of self-assembling by association/interaction processes 2 1.2 The nature of forces and types of interactions involved in self-assembly of macromolecules 2 1.3 Hydrogels and their role in drug conception and development 5 1.3.1 Organogels and micelles for drug delivery 7 1.4 Self-assembling phenomena in solid dosage forms 7 1.4.1 Hydrogen association and flexibility of chains 7 1.4.2 Ionically stabilized excipients 10 1.4.2.1 Two-speed self-assembled monolithic devices 10 1.4.3 Hydrophobic stabilization of excipients and drug release mechanisms 11 1.4.3.1 The concept of self-assembling by inclusion processes 14 1.4.3.2 Inclusion complexes of starch with fatty bioactive agents 14 1.4.3.3 Inclusion complexes and hydrophobic assembly of starch excipients 15 1.5 Conclusions 17 References 17 1.1 The concept of self-assembling
Self-assembling can be defined as the capacity of certain molecules, macromolecules, or composite materials to associate themselves and to form complexes and/or networks or other structures with novel properties. Some of these are particularly useful in technological and biomedical applications. The self-assembling process can occur at the molecular (including macromolecular) level and as a supramolecular organization (Lehn, 1988, 1990, 1993, 1995; Phlip, 1996). Molecular self-assembly is omnipresent in nature and has generated new approaches in biomedicine, biotechnology, nanotechnology, polymer fields, and, recently, pharmaceutical formulation, particularly in drug delivery. It is a spontaneous organization of molecules under thermodynamic equilibrium conditions into a more stable structure that is stabilized by arrangements through noncovalent weak (Whitesides et al., 1991; Ball, 1994), but numerous, hydrogen associations, ionic bonds, and van der Waals interactions based on chemical complementarity and structural compatibility. Their huge number can generate rapid and stable assembling of excipient matrices. Some of these aspects are discussed in this chapter, but they are presented in more detail in Chapters 2–5. The self-assembling process can occur: 1. By association (with themselves and/or with different structures) via various types of interactions (hydrogen associations, van der Waals forces, hydrophobic/stabilization, ionic interactions, click noncovalent recognition) 2. By inclusion/complexation (structure A will include structure B), such as inclusion of complexes of starch (clathrates), like iodine blue inclusion complexes of starch (known since the early 1930s) or of cyclodextrins (Loftsson and Duchêne, 2007), and the recently studied Rotaxanes with various oligomers (Ariga et al., 2008). Self-assembled structures are largely discussed in relation to particular types of excipients and in relation to drug delivery processes in other chapters. This section aims only to define various types of interactions and to briefly discuss their possible involvement in self-assembled organization of excipients. 1.1.1 The concept of self-assembling by association/interaction processes
Macromolecular systems can markedly increase their size by covalent links between different components via cross-linking (such as chains of polyacrylamide cross-linked by the N,N'-bisacrylamide cross-linker, to produce a tridimensional material) (Sairam et al., 2006; Kopecek and Kopecková, 2010). In contrast, the origin of self-assembling is related to the ability of certain (macro)molecules to interact noncovalently with (macro)molecules of the same type or different types, generating aggregates or composite materials. This kind of assembling resulting in aggregation or reciprocal stabilization between similar or different molecular items (structures or sequences) can be considered self-assembling by association. Numerous macromolecules (polysaccharides or synthetic polymers) used as pharmaceutical excipients exhibit a strong capacity to structure the pharmaceutical forms and/or to modulate the drug release because of their assembling properties. This structuring ability resides, in most cases, in the self-assembling capacity of polymeric excipients that is exerted through noncovalent (hydrogen bonding, van der Waals forces, p–p interactions, and/or ionic) stabilization. An understanding of such supramolecular assemblies will create tools for drug conceptors to optimize drug formulations in terms of drug release profiles, pill shapes, and their stability in physiological fluids. 1.2 The nature of forces and types of interactions involved in self-assembly of macromolecules
Because there are various types of interactions involved in self-assembling processes, the nature of the forces involved will modulate the variety of structural organization for different matrices. Thus, for each material, the various shapes and sizes of different forms that can be obtained can rely on molecular or supramolecular self-assembly. These different interactions can be involved in association and stabilization of carbohydrates, proteins, nucleic acid, lipids or other materials of natural, synthetic, or semisynthetic origin. The self-assembly concept is strongly related to supramolecular chemistry (Lehn, 1988, 1990, 1993, 1995). The same forces inducing the stabilization of molecular assembling are involved in supramolecular organization, but with the contribution of a larger number of interactions and with the involvement of structural complementarity and recognition phenomena. Some aspects of supramolecular assembling are discussed in Chapter 6 (protein associative interactions), and related materials for implants and stents are discussed in Chapter 7. These associations can be classified in terms of types of interactions involved in self-stabilization, as follows: 1. Ionic stabilization 2. Dipole–dipole interactions a. Ion–dipole and ion-induced dipole forces b. Hydrogen bonding 3. p–p interactions 4. Van der Waals forces a. Keesom (permanent dipole) force b. Debye (induced dipole) force 5. Hydrophobic associations Details of these forces and their roles in self-assembling can be found in the work by Ege (2003). In terms of relative strength, these interaction forces can be classified as shown in Table 1.1. Table 1.1 Relative strength of different associative bonds Bond type Dissociation energy: kcal/mol (Ege, 2003) Ionic bonds 300–400 Hydrogen bonds 12–16 Dipole–dipole 0.5–2 Van der Waals forces <1 Knowledge of such interactive forces is important because it allows formulators to anticipate possible (desired or undesired) excipient–excipient or drug–excipient interactions. Ionic bonds: Among the noncovalent bonds, the electrostatic interactions are robust and can form rapidly polyelectrolyte complexes when anionic macromolecules (i.e., carboxylic polymers) are treated with cationic (i.e., polyamines) macromolecules. Ionic self-assembly is presented in Chapter 4. Hydrogen bonding: Hydrogen bonding is an interaction between polar molecules in which hydrogen (H) is...