POLYSACCHARIDES AS BUILDING BLOCKS FOR NANOTHERAPEUTICS

Tony FrancisDepartment of ChemistrySt. Mary’s college Manarkadu

Introduction Over the past two decades nanoparticles

(NPs)-based therapeutics have been introduced for the treatment of cancer, diabetes, allergy, infections and inflammation.

Of the available NP systems polysaccharides are the most outstanding one because of there virtues such as biocompatibility, biodegradability, low toxicity, low cost and there ease of chemical modification

Classification Carbohydrates

Monosaccharides- A Carbohydrate that cannot be hydrolysed further to give simple units of polyhydroxy aldehyde or ketone.

Oligosaccharides- Carbohydrate that can yield two to ten monosaccharide unit on hydrolysis.

Polysaccharides- Polymers of monosaccharides

joined together by glycosidic linkage.

Polysaccharides classification based on there origin

Plant origin – Cellulose, Pectin and guar gum Animal origin – Chitosan, Heparin and

Hyaluronan Algal origin – Alginate and Carrageenan Microbial origin- Dextran and Xanthan gum Marine origin- Agar and Agarose

Classification based on the monomer groups

Homopolysaccharides or Homoglycans- They are polysaccharides which consists of only a single type of monosaccharide unit. Ex.- cellulose, starch etc.

Heteropolysaccharides or Heteroglycans -They are polysaccharides built up of two or more different monomeric units. Ex.- Chitosan, Hyaluronan etc.

Starch It is a glucose polymer Made up of a mixture of amylose (15-

20%) and amylopectin (80-85%) They can be hydrolysed by enzyme

called amylase

•Potato, rice, wheat and maize are the major sources of starch in human food.

Cellulose

•It is the most abundant polysaccharide.•It is found in all plants as the major structural component of the cell wall.•It is the β-isomer of amylose consisting of β-(1,4)-linked glucose residues.

Glycogen It is energy reserve for animals It is the chief form of carbohydrates

stored in animal body It is insoluble in water. It turns red when

mixed with iodine. It is composed of branched chain of

glucose residues. It is stored in liver and skeletal muscles.

Chitin

Chitin is considered the most abundant biopolymer in nature after cellulose

Chitin is the principal structural component of the exoskeleton of invertebrates

There are serious difficulties in modification reactions to prepare well-defined derivatives of chitin since it is insoluble in common solvents

Chitosan

Chitosan is produced from the deacetylation of chitin

It is a hemostatic material from which blood anticoagulants and antithrombogenic agents have been formed

It is positively charged and therefore can interact with negatively charged molecules such as negatively charged polysaccharides, polyanions, nucleic acid and negatively charged proteins

•It is obtained commercially from shrimp or crab shell chitin•Chitosan is relatively inexpensive, non-toxic• They possesses reactive amino groups and has the capability to accelerate the healing of wound in human•It confers considerable antibacterial activity against a broad spectrum of bacteria•Chitosan has broad applications in the biomedical field ,paper production, heavy metal chelating agents and waste removalCS based delivery systems have been described for nasal, ocular, oral, parenteral and transdermaldrug delivery

Pullulan

It is neutral, homopolysaccharide consisting of a–(1,6)-linked maltotriose residues

Its unique linkage pattern contributes to exceptional physiochemical properties such as adhesiveness, water solubility and relatively low viscosity upon dissolving in water

Pullulan and its derivatives have been used industrially in foods and pharmaceuticals.

Heparin

Due to high content of sulfo and carboxyl groups, heparin has the highest negative charge density of any known biological molecule

It is extracted mainly from mucosal tissues of porcine and bovine

Heparin has been used as an anticoagulant since the 1930s

Beyond its anticoagulant activity, it shows antiviral activity and regulate angiogenesis

Hyaluronic Acid Also called hyaluronan or hyaluronate or

HA It is a linear polysaccharide consisting of

alternating units of N-acetyl-D-glucosamine and glucuronic acid, being found in virtually every tissue of invertebrates

HA can form three-dimensional structures in solution with extensive intramolecular hydrogen bonding

It has the ability to promote angiogenesis, to modulate wound site inflammation by acting as a free radical scavenger

•HA is water-soluble and forms highly viscous solutions with unique viscoelastic properties

Dextran Dextran is a water-soluble polysaccharide

which consists mainly of α-(1, 6) linked D-glucopyranose residues with a low percentage of α-1,2, α-1,3 and α-1,4 linked side chains

Dextran is used as a blood plasma substitute due to its non-toxicity

Dextran has wide applications in novel drug delivery systems as a polymeric carrier

•Dextran is also a suitable polymer to be used for the preparation of hydrogels, which are becoming increasingly important in the biomedical, pharmaceutical, biotechnological and environmental fields.

Cyclodextrins They are natural cyclic oligomers of a-

(1,4)linked-glucopyranosyl that are produced from starch by enzymatic conversion.

CDs have a hydrophilic exterior and a hydrophobic cavity that enables them to act as hosts to hydrophobic molecules

There are three main members of the CD family, composed of six, seven and eight glucose units and known as α-, β- and ɤ-CD, respectively.

•The shielding ability of CDs helps in stabilize biomolecules from adverse effects of non-specific interactions, which in turn make CDs suitable for drug delivery systems

Pectins

Pectins are polysaccharides occurring in all plants primarily in their cell wall

They act as intracellular cementing material that gives body to fruits and helps them keep their shape

They are composed of D–galactopyranosyl uronic acid units, which are a–(1,4)–linkage contain methyl esters and acetyl groups

The main mechanisms of nanoparticlepreparation from polysaccharides 1. Covalent cross-linking

2. Ionic cross-linking

3. Polyelectrolyte complexes (PEC)

4. Self-assembly

5. Polysaccharide –drug conjugate

Why is Drug Delivery important?

By using DD the ability to engineer controlled localized delivery of drugs might contribute to the :-

1) Efficiency of the treatment and 2) Reduces the side effects.

Enhanced permeability and retention (EPR) effect & Drug Delivery

It is the property by which certain sizes of molecules tend to accumulate in tumor tissue much more than they do in normal tissues.

This is because the tumors can induce blood vessel growth (angiogenesis) by secreting various growth factors which helps in tumor expansion

REQUIREMENTS FOR AN EFFICIENT DRUG DELIVERY VEHICLE

THEY SHOULD BE :-1. NON-TOXIC2. BIOCOMPATIBLE3. HIGH DRUG LOADING CAPACITY4. CONTROL RELEASE AND AVIOD THE “BURST

EFFECT”5. CONTROL MATRIX DEGRADATION AND

ENGINEER ITS SURFACE6. BE DETECTABLE BY VARIOUS IMAGING

TECHNIQUES

IMPORTANT DD SYSTEMS POLYMERIC NANOPARTICLES QUANTUM DOTS METALLIC NANOPARTICLES POLYSACCHARIDES LIPOSOMES CERAMIC NANOPARTICLES CARBON NANOPARTICLES DENDRIMERS

All these systems can be divided

ORGANIC

POLYMERIC NPS LIPOSOMES POLYSACCHARIDE

S DENDRIMERS CARBON NPS

INORGANIC

QUANTUM DOTS METALLIC NPS CERAMIC NPS

Conclusion So we can say that of all the available drug

delivery systems the polysaccharide NP DD systems are the most efficient because of there outstanding virtues, such as biocompatibility, biodegradability, low toxicity low cost and ease of chemical modification

THANK YOU ….