natural polymer

Natural-based polymers for biomedical applications

 examines the sources, processing and properties of natural based polymers for biomedical applications
 - explains how the surfaces of polymer based biomaterials can be modified to improve their functionality
 - discusses the use of natural based polymers for hydrogels in tissue engineering, and inparticular natural gelling polymers for encapsulation and regenerative medicine
 - summarises the use of natural based polymers as delivery systems for drugs, hormones, enzymes and growth factors

Polymers from natural sources are particularly useful as biomaterials and in regenerative medicine, given their similarity to the extracellular matrix and other polymers in the human body. This important book reviews the wealth of research on both tried and promising new natural-based biomedical polymers, together with their applications as implantable biomaterials, controlled-release carriers or scaffolds for tissue engineering.

The first part of the book reviews the sources, processing and properties of natural-based polymers for biomedical applications. Part two describes how the surfaces of polymer-based biomaterials can be modified to improve their functionality. The third part of the book discusses the use of natural-based polymers for biodegradable scaffolds and hydrogels in tissue engineering. Building on this foundation, Part four looks at the particular use of natural-gelling polymers for encapsulation, tissue engineering and regenerative medicine. The penultimate group of chapters reviews the use of natural-based polymers as delivery systems for drugs, hormones, enzymes and growth factors. The final part of the book summarises research on the key issue of biocompatibility.

Introduction of patural polymer- In the area of drug delivery, various polymers are involved. The earlier polymers were natural in origin. The natural polymers were found to be fraught with many formulation Problems such instability, irreproducibility, changes in aesthetics on storage, uncontrollable Formulation characteristics, etc. As a result new designer molecules were sought for to solve Some of the problems. Some of the natural polymers were largely polysaccharide gums such as acacia, guar, xanthan, agar, tragacanth, etc. These may have their origin plant, seaweed or even fungi. Some bacteria are known to produce polysaccharides that may be useful in medical and pharmaceutical practices. A few polymers may be of animal origin such as gelatin, serum albumin, liposomes, etc. On the other hand, synthetic polymers are either modified from natural polymers or completely synthesized from synthetic monomers. They process properties that seem to relatively address the problems of instability, irreproducibility, changes in aesthetics on storage, uncontrollable formulation characteristics. The environment of use in the body is often considered in the preparation of these polymers. Good examples are the derivates of the acrylic resins, vinyl polymers, cellulose polymers, etc. Various aspects of these two classes of polymers are presented in this chapter.

Natural Biopolymers in Gene therapy Delivery
Chukwuemeka S. Nworu, Edward C. Nwanegbo, and Charles O. Esimone

Effective delivery of therapeutic genes to target cells is an essential goal of all innovative gene therapy endeavours and recombinant vaccine technology. Current use of viral vectors in achieving this goal has been associated with minimal success and plethora of unwanted adverse events. As a result, there is an ongoing search for suitable vector platforms for the delivery of therapeutic genes to target cells. Such agent should be easily manipulated to accommodate small and large gene inserts and safely deliver Transgenes. This will ensure effective expression of the gene in target cells. The resulting optimal expression of this gene may correct defective or deficient gene in individuals receiving gene therapy. This chapter examines the applications of biopolymers as non-viral gene delivery vectors either alone or as copolymers.


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Particulate Drug Delivery: Recent Applications of Natural Biopolymers
Anthony A. Attama and Philip F. Builders

Polymers fall into three broad categories: natural, semi-synthetic and synthetic. Polymers are widely used in pharmaceutical systems as drug carriers, adjuvants, suspending and emulsifying agents. The word "polymer" which means "many parts", is derived from the Greek words poly, meaning "many," and meros, meaning "parts". Polymers are widely found in nature and occur in many forms. The human body contains many natural polymers such as proteins and nucleic acids, while cellulose is the main structural component of plants. Cellulose, starch, lignin, chitin, and various polysaccharides are of natural origin. These materials and their derivatives offer a wide range of properties and applications in drug delivery. Natural polymers are usually biocompatible and biodegradable. In this chapter, sources and applications of natural biopolymers in particulate drug delivery systems such as microparticles and nanoparticles, which are currently widely investigated as drug delivery systems, were discussed.

Challenges of the Use of Natural Biopolymers in Drug Delivery
N.C. Obitte and E.O. Omeje

Drug delivery and pharmacokinetics have remained important components of therapeutic and biomedical practice for many decades. In recent time, the world has witnessed rapid progress in developments of different drug delivery protocols, especially as it regards the use of degradable biopolymers. This became a viable research and economic venture with parallel progress in inter-related fields of biomaterial science, biotechnology, nanotechnology and pharmacology. Recent advances in material science, biomaterial development and tissue engineering are changing the face of medicine in the present age. Biopolymers and drug delivery systems offer the “ideal” conceptual framework for improving the efficacy of existing drug formulations and developing new treatments. Interestingly, there are extensive researches so far carried out in the area of biodegradable materials for controlled release of drug which circumvents the need for removal of nondegradable drug-depleted devices. Many biodegradable polymers have been evaluated for their suitability as matrix for drugs, including polyesters, polycarbonates, natural and synthetic polyamides, phosphate esters, polyphosphazenes and polyanhydrides. Current and novel drug delivery approaches involve the application of these polymers in a variety of devices, including biodegradable polymer shape-memory polymers, targeted nanoparticle conjugates and miniaturized drug delivery devices. These approaches have greatly improved the delivery of drugs to target sites that would have been ordinarily impossible by conventional therapeutic routes. In this chapter, we will discus some key recent and relevant advances in the use of biopolymers for drug delivery. Thereafter, the challenges still ahead will be presented. In all, biopolymers promise rewarding prospects for the world in this 21st century and beyond.

Particulate Drug Delivery: Recent Applications of Natural Biopolymers
Anthony A. Attama and Philip F. Builders

Polymers fall into three broad categories: natural, semi-synthetic and synthetic. Polymers are widely used in pharmaceutical systems as drug carriers, adjuvants, suspending and emulsifying agents. The word "polymer" which means "many parts", is derived from the Greek words poly, meaning "many," and meros, meaning "parts". Polymers are widely found in nature and occur in many forms. The human body contains many natural polymers such as proteins and nucleic acids, while cellulose is the main structural component of plants. Cellulose, starch, lignin, chitin, and various polysaccharides are of natural origin. These materials and their derivatives offer a wide range of properties and applications in drug delivery. Natural polymers are usually biocompatible and biodegradable. In this chapter, sources and applications of natural biopolymers in particulate drug delivery systems such as microparticles and nanoparticles, which are currently widely investigated as drug delivery systems, were discussed.

Polysaccharides as carriers of bioactive agents for medical applications
P Pawar, W Jadhav, S Bhusare and R Borade, Dnyanopasak College, India, S Farber, D Itzkowitz and A Domb, The Hebrew University, Jerusalem, Israel
 - Introduction
 - Starch
 - Cellulose
 - Heparinoid (sulfated polysaccharides)
 - Dextran
 - Pectin
 - Arabinogalactan
 - Drug conjugated polysaccharides
 - Dextrans
 - Mannan
 - Pullulan
 - Polysaccharides macromolecule-protein conjugates
 - Cationic polysaccharides for gene delivery
 - Diethylaminoethyl-dextran
 - Polysaccharide-oligoamine based conjugates
 - Chitosan
 - Applicatons of polysaccharides as drug carriers
 - Applications of dextran conjugates
 - Site-specific drug delivery
 - Pectin drug site specific delivery
 - Liposomal drug delivery
 - References
Purification of naturally occurring biomaterials
M N Gupta, Indian Institute of Technology Delhi, India
 - Introduction
 - Classes of naturally occurring biomaterials
 - Downstream processing of small molecular weight natural products
 - Purification strategies for proteins
 - Purification of lipids
 - Purification of polysaccharides
 - Purification of nucleic acids
 - Purification of complex biomaterials
 - Future trends
 - Sources of further information
 - Acknowledgements
 - References
Processing of starch-based blends for biomedical applications
R A de Sousa, V M Correlo, S Chung, N M Neves, J F Mano and R L Reis, University of Minho, Portugal
 - Introduction
 - Starch
 - Starch-based blends
 - Conclusions
 - References
Controlling the degradation of natural polymers for biomedical applications
H S Azevedo, T C Santos and R L Reis, University of Minho, Portugal
 - Introduction
 - The importance of biodegradability of natural polymers in biomedical applications
 - Degradation mechanisms of natural polymers and metabolic pathways for their disposal in the body
 - Assessing the in vitro and in vivo biodegradability of natural polymers
 - Controlling the degradation rate of natural polymers
 - Concluding remarks
 - Acknowledgements
 - References
Smart systems based on polysaccharides
M N Gupta and S Raghava, Indian Institute of Technology Delhi, India
 - What are smart materials?
 - Chitin and chitosan
 - Alginates
 - Carrageenans
 - Other miscellaneous smart polysaccharides and their applications
 - Polysaccharide-based composite materials
 - Future trends
 - Acknowledgement
 - Sources of further information and advice
 - References

PART 2 SURFACE MODIFICATION AND BIOMIMETIC COATINGS

Surface modification of natural-based biomedical polymers
I Pashkuleva, P M López-Pérez and R L Reis, University of Minho, Portugal
 - Introduction
 - Some terms and classifications
 - Wet chemistry in surface modification
 - Physical methods for surface modification
 - Grafting
 - Bio-approaches: mimicking the cell-cell interactions
 - Future trends
 - Acknowledgments
 - References
New biomineralization strategies for the use of natural-based polymeric materials in bone-tissue engineering
I B Leonor, S Gomes, P C Bessa, J F Mano and R L Reis, University of Minho and M Casal, CBMA - Molecular and Environmental Biology Center, University of Minho, Portugal
 - Introduction
 - The structure, development and mineralization of bone
 - Bone morphogenetic proteins in tissue engineering
 - Bio-inspired calcium-phosphate mineralization from solution
 - General remarks and future trends
 - Acknowledgments
 - References
Natural-based multilayer films for biomedical applications
C Picart, Université Montpellier, France
 - Introduction
 - Physico-chemical properties
 - Different types of natural-based multilayer films for different applications
 - Bioactivity, cell adhesion, and biodegradability properties
 - Modulation of film mechanical properties
 - Future trends
 - Sources of further information and advice
 - References
Peptide modification of polysaccharide scaffolds for targeted cell signaling
S Lévesque, R Wylie, Y Aizawa and M Shoichet, University of Toronto, Canada
 - Introduction
 - Polysaccharide scaffolds in tissue engineering
 - Peptide immobilization
 - Measurement
 - Challenges associated with peptide immobilization
 - Tissue engineering approaches targeting cell signalling
 - References

PART 3 BIODEGRADABLE SCAFFOLDS FOR TISSUE REGENERATION

Scaffolds based on hyaluronan derivatives in biomedical applications
E Tognana, Fidia Advanced Biopolymers s.r.l., Italy
 - Introduction
 - Hyaluronan
 - Hyaluronan-based scaffolds for biomedical applications
 - Clinical applications
 - Future trends
 - Sources of further information and advice
 - References
Electrospun elastin and collagen nanofibers and their application as biomaterials
R Sallach and E Chaikof, Emory University/Georgia Institute of Technology, USA
 - Introduction
 - Electrospinning as a biomedical fabrication technology
 - Generation of nanofibers with controlled structures and morphology
 - Generation of collagen and elastin small-diameter fibers and fiber networks
 - Biological role of elastin
 - Generation of crosslinked fibers and fiber networks
 - Multicomponent electrospun assemblies
 - Future trends
 - References
Starch-polycaprolactone based scaffold for bone tissue engineering
M E Gomes, J T Oliveira, M T Rodrigues, M I Santos, K Tuzlakoglu, C A Viegas, I R Diaz and R L Reis, University of Minho, Portugal
 - Introduction
 - Starch+e-polycaprolactone (SPCL) fiber meshes
 - SPCL-based scaffold architecture, stem cell proliferation and differentiation
 - In vivo functionality of SPCL fiber-mesh scaffolds
 - Cartilage tissue engineering using SPCL fiber-mesh scaffolds
 - Advanced scaffold design for bone tissue engineering
 - Nano/micro fiber combined scaffold - innovative architecture
 - Conclusions
 - References
Chitosan-based scaffolds in orthopaedic applications
K Tuzlakoglu and R L Reis, University of Minho, Portugal
 - Introduction: Chemical and physical structure of chitosan and its derivatives
 - Production methods for scaffolds based on chitosan and its composites or blends
 - Orthopaedic applications
 - Conclusions and future trends
 - Acknowledgements
 - References
Elastin-like systems for tissue engineering
J Rodriguez-Cabello, A Ribeiro, J reguera, A Girotti and A Testera, Universidad de Valladolid, Spain
 - Introduction
 - Genetic engineering of protein-based polymers
 - Genetic strategies for synthesis of protein based polymers
 - State-of-the-art in genetically-engineered protein-based polymers (GEBPs)
 - Elastin-like polymers
 - Self-assembly behaviour of peptides and proteins
 - Self-assembly of elastin-like polymers (ELPs)
 - Biocompatibility of ELPs
 - Biomedical applications
 - ELPs for drug delivery
 - Tissue engineering
 - Self-assembling properties of ELPs for tissue engineering
 - Processability of ELPs for tissue engineering
 - Future trends
 - References
Collagen-based scaffolds for tissue engineering
G Chen, N Kawazoe and T Tateishi, National Institute for Materials Science, Japan
 - Introduction
 - Structure and property of collagen
 - Collagen sponge
 - Collagen gel
 - Collagen–glycosoaminoglycan (GAG) scaffolds
 - Acellularized scaffolds
 - Hybrid scaffolds
 - Future trends
 - References
Polyhydroxyalkanoate and its potential for biomedical applications
P Furrer and M Zinn, EMPA and S Panke, Swiss Federal Institute of Technology (ETH), Switzerland
 - Introduction
 - Biosynthesis
 - Chemical digestion of PHA-biomass
 - Purification of PHA
 - Potential applications of PHA in medicine and pharmacy
 - Conclusions and future trends
 - References
Electrospinning of natural proteins for tissue engineering scaffolding
P I Lelkes, M Li, A Perets, L Lin, J Han and D Woerdeman, Drexel University, USA
 - Introduction
 - The electrospinning process
 - Electrospinning natural animal polymers
 - Electrospinning blends of synthetic and natural polymers
 - Electrospinning novel natural ‘green’ plant polymers for tissue engineering
 - Soy proteins
 - Corn zein
 - Wheat gluten
 - Blends of synthetic and plant proteins
 - Cellular responses to electrospun scaffolds: does fiber diameter matter?
 - Conclusions and future trends
 - Sources of further information and advice
 - References

PART 4 NATURALLY-DERIVED HYDROGENS: FUNDAMENTALS, CHALLENGES AND APPLICATIONS IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE

Hydrogels from polysaccharide-based materials: fundamentals and applications in regenerative medicine
J T Oliveira and R L Reis, University of Minho, Portugal
 - Introduction: definitions and properties of hydrogels
 - Applications of hydrogels produced from different polysaccharides in tissue engineering and regenerative medicine
 - Agarose
 - Alginate
 - Carrageenan
 - Cellulose
 - Chitin/chitosan
 - Chondroitin sulphate
 - Dextran
 - Gellan
 - Hyaluronic acid
 - Starch
 - Xanthan
 - Conclusions
 - References
Alginate hydrogels as matrices for tissue engineering
H Park and K-Y Lee, Hanyang University, South Korea
 - Introduction
 - Properties of alginate
 - Methods of gelling
 - Application of alginate hydrogels in tissue engineering
 - Summary and future trends
 - References
Fibrin matrices in tissue engineering
B Tawil, H Duong and B Wu, University of California, USA
 - Introduction
 - Fibrin formation
 - Fibrin use in surgery
 - Fibrin matrices to deliver bioactive molecules
 - Fibrin - cell constructs
 - Mechanical characteristics of fibrin scaffolds
 - Future trends
 - Conclusions
 - References
Natural-based polymers for encapsulation of living cells: fundamentals, applications and challenges
P De Vos, University Hospital of Groningen, The Netherlands
 - Introduction
 - Approaches to encapsulation; Materials and biocompatibility issues
 - Physico-chemistry of microcapsules and their biocompatibility
 - Immunological considerations
 - Conclusions and future trends
 - Sources of further information and advice
 - References
Hydrogels for spinal cord injury regeneration
A J Salgado, N Sousa, N A Silva, N M Neves and R L Reis, University of Minho, Portugal
 - Introduction
 - Brief insights on central nervous system biology
 - Current approaches for SCI repair
 - Hydrogel-based systems in SCI regenerative medicine
 - Conclusions and future trends
 - Acknowledgments
 - References

PART 5 SYSTEMS FOR THE SUSTAINED RELEASE OF MOLECULES

Particles for controlled drug delivery
E T Baran and R L Reis, University of Minho, Portugal
 - Introduction
 - Novel particle processing methods
 - Hiding particles: the stealth principle
 - Finding the target
 - Delivery of bioactive agents at the target site and novel deliveries
 - Viral delivery systems
 - Conclusions
 - Acknowledgements
 - References
Thiolated chitosans in non-invasive drug delivery
A Bernkop-Schnürch, Leopold-Franzens University, Austria
 - Introduction
 - Thiolated chitosans
 - Properties of thiolated chitosans
 - Drug delivery systems
 - In vivo performance
 - Conclusions
 - References
Chitosan-polysaccharide blended nanoparticles for controlled drug delivery
J M Alonoso and F M Goycoolea, Universidad de Santiago de Compostela, Spain and I Higuera-Ciapara, Centro de Investigación en Alimentación y Desarrallo, Mexico
 - Introduction
 - Polysaccharides in nanoparticle formation
 - Nanoparticles constituted from chitosan
 - Drug delivery properties and biopharmaceutical applications
 - Hybrid nanoparticles consisting of chitosan and other polysaccharides
 - Future trends
 - Sources of further information and advice
 - Acknowledgements
 - References

PART 6 BIOCOMPATIBILITY OF NATURAL-BASED POLYMERS

In vivo tissue response to natural-origin biomaterials
T C Santos, A P Marques and R L Reis, University of Minho, Portugal
 - Introduction
 - Inflammation and foreign-body reactions to biomaterials
 - Role of host tissues in biomaterials implantation
 - Assessing the in vivo tissue responses to natural-origin biomaterials
 - Controlling the in vivo tissue reactions to natural-origin biomaterials
 - Final Remarks
 - Acknowledgements
 - References
Immunological issues in tissue engineering
N Rotter, Ulm University, Germany
 - Introduction
 - Immune reactions to biomaterials
 - Host reactions related to the implant site
 - Immune reactions to different types of cells
 - Immune reactions to in vitro engineered tissues
 - Immune protection of engineered constructs
 - Strategies directed towards reactions to biomaterials
 - Strategies directed towards reactions to implanted cells
 - Future trends
 - Sources of further information and advice
Biocompatibility of hyaluronic acid: from cell recognition to therapeutic applications
K Ghosh, Children’s Hospital and Harvard Medical School, USA
 - Introduction
 - Native hyaluronan
 - Therapeutic implications of native hyaluronan
 - Engineered hyaluronan
 - Implications for regenerative medicine
 - Conclusions
 - Future trends
 - References
Biocompatibility of starch-based polymers
A P Marques, R P Pirraco and R L Reis, University of Minho, Portugal
 - Introduction
 - Starch-based polymers in the biomedical field
 - Cytocompatibility of starch-based polymers
 - Immunocompatibility of starch-based polymers
 - Conclusions
 - Acknowledgments
 - References
Vascularisation strategies in tissue engineering
M I Santos and R L Reis, University of Minho, Portugal
 - Introduction
 - Biology of vascular networks - angiogenesis versus vasculogenesis
 - Vascularization: the hurdle of tissue engineering
 - Neovascularization of engineered bone
 - Strategies to enhance vascularization in engineered grafts
 - In vivo models to evaluate angiogenesis in tissue engineered products
 - Future trends
 - Sources of further information and advice
 - References

The word polymer is name comes from greek words. Polymer is a substance which consists of molecules which are at least around multiples of low molecules weight units. Monomer is a small molecule which joins with every other from a polymer. The types of natural polymers follow.

Types of Natural Polymers

     The natural polymers obtained from nature are known as natural polymers. There are five types available in natural polymers.

·         Starch

·         Cellulose

·         Proteins

·         Nucleic Acid

·         Natural rubber

Starch

     It is a polymer of glucose. It is a principal food store of plants.

Cellulose

     It is also polymer glucose. It is principal structural material of the plants. Both starch and cellulose are produced by plants through photosynthesis.

Proteins

     These are polymers of alpha amino acids. They have usually 20 to 100 alpha amino acids joined together in a highly organized arrangement. These are building group of animals.

Nucleic Acids

    These are polymers has a variety of nucleotides. RNA and DNA are ordinary nucleotides.

Natural rubber

     It is a polymer of unsaturated hydrocarbon, 3 butadiene known as isoprene. It is finding from latex of rubber trees.

Examples for Natural Polymer

1.     Starch:  Starch is a best example of natural polymer.  Starch is also one of a polymer of glucose.  It is a chief food reserve of plants.

2.     Cellulose:  Plants are made of a polymer is called cellulose.  It is also one of a polymer of glucose.  It is one of the examples of natural polymer.  It is a chief structural material of the plants.  Both starch and cellulose are produced by plants during photosynthesis.

3.     Proteins:  These are polymers of α-amino acids.  They have generally 20 to 100 α-amino acids joined together in a highly organized arrangement.  These are building block of animals.  It is an example of natural polymer.

4.     Nucleic acids:  These are polymers of various nucleotides.  RNA and DNA are common nucleotides.

5.     Natural rubber:  It is a polymer of unsaturated hydrocarbon, 2-methyl-1, 3-butadiene, called isoprene.  It is obtained from latex of rubber trees.  Natural rubber is a gummy material, has poor elasticity.  It becomes permanently deformed when stretched.  However, a few cross links are introduced in the chain.

6.     Biopolymers:  Polysaccharides (starch, cellulose), protein and nucleic acid are called biopolymers and it is an example of natural polymer.

Introduction for natural polymers

       Polymers are macromolecules (giant molecules of higher molecular weight) formed by the repeated linking of large number of small molecules called monomers. The polymers obtained from nature (plants and animals) are called natural polymers.  Natural polymer is one of the types of polymers.  These natural polymers are found in plants and animals.  Examples for natural polymer are proteins, cellulose, starch, resin and natural rubber.

Types of Natural Polymer

Polymers may be classified in more than one manner.  The conventional classification is denoted in following

Polymer:

1. Natural polymers

     Organic

·          Cellulose

·          RNA and DNA

·          Proteins

·          Polypeptides

     Inorganic

·         Clay (silicates)

·         Synthetic polymers

    Organic

·         Polyethylene

·         Polypropylene

·         Polyesters

·         Polyurethanes

·         Polyvinyl

     Inorganic

·         Silicones.

• Natural Polymers :

             a) Collagen

•                    b) AlbuminNatural polymers remains the primary choice of formulator because

  - They are natural products of living organism

  - Readily available

  - Relatively inexpensive

  - Capable of chemical modification

•       Moreover, it satisfies most of the ideal requirements of polymers.

•       But the only and major difficulty is the batch- to-batch reproducibility and purity of the sample.

             c) Casein

             d) gelatin

•       Examples :

      1) Proteins :

            -  Collagen :  Found from animal tissue.

               Used in absorbable sutures, sponge             wound dressing, as drug delivery vehicles

            -  Albumin :  Obtained by fabrication of        blood from healthy donor.

               Used as carriers in nanocapsules & microspheres

            -  Gelatin : A natural water soluble polymer

                        Used in capsule shells and also as       coating material in microencapsulation

2) Polysaccharides :

            -  Starch : 

                                    Usually derivatised by introducing     acrylic groups before manufactured   into             microspheres.

                        Also used as binders.

            -  Cellulose :

                                     Naturally occuring linear        polysaccharide. It is insoluble in water but     solubility can be obtained by substituting -OH             group.

                        Na-CMC is used as thickner, suspending       agent, and film formers.

3) DNA &RNA :

                                    They are the structural unit of our body.        DNA is the blueprint that determines everything             of our body.