Chitosan is considered as one of the most promising biomaterials of the 21st century on accounts of its versatile nature, excellent biodegradability, biocompatibility, antimicrobial activity, non-toxicity and wide applications. Chitosan is derived from Chitin, a second most abundantly available natural polymer after cellulose.
Chitin is naturally found in the exoskeleton of shellfish such as crabs and shrimps, and in the cell membranes of fungi, yeasts, and other microorganisms. Chitin is not soluble in dilute acids, whereas chitosan is soluble in dilute acids.
Chitosan is primarily composed of glucosamine and N-acetyl glucosamine residues with a 1, 4-β-linkage. The presence of primary amines (-NH2) in chitosan gives it a net positive charge and is important for its biological properties.
2. WHAT IS A
CHITOSAN??
• CHITOSAN IS CONSIDERED AS ONE OF THE MOST PROMISING
BIOMATERIALS OF THE 21ST CENTURY ON ACCOUNTS OF ITS
VERSATILE NATURE, EXCELLENT BIODEGRADABILITY,
BIOCOMPATIBILITY, ANTIMICROBIAL ACTIVITY, NON-TOXICITY
AND WIDE APPLICATIONS. CHITOSAN IS DERIVED FROM CHITIN,
A SECOND MOST ABUNDANTLY AVAILABLE NATURAL POLYMER
AFTER CELLULOSE.
• CHITIN IS NATURALLY FOUND IN THE EXOSKELETON OF
SHELLFISH SUCH AS CRABS AND SHRIMPS, AND IN THE CELL
MEMBRANES OF FUNGI, YEASTS, AND OTHER
MICROORGANISMS. CHITIN IS NOT SOLUBLE IN DILUTE ACIDS,
WHEREAS CHITOSAN IS SOLUBLE IN DILUTE ACIDS.
• CHITOSAN IS PRIMARILY COMPOSED OF GLUCOSAMINE AND N-
ACETYL GLUCOSAMINE RESIDUES WITH A 1, 4-Β-LINKAGE. THE
PRESENCE OF PRIMARY AMINES (-NH2) IN CHITOSAN GIVES IT
A NET POSITIVE CHARGE AND IS IMPORTANT FOR ITS
BIOLOGICAL PROPERTIES.
3. WORLDWIDE DISTRIBUTION
OF CHITIN AND CHITOSAN IN
NATURE
• CHITIN IS NATURALLY DISTRIBUTED IN THE ENDOSKELETON
OF CEPHALOPODA, THE EXOSKELETON OF ARTHROPODS AND
THE CELL MEMBRANE OF FUNGI AND PLANTS.
• EACH YEAR 6-8 MILLION TONS OF CRUSTACEAN WASTE
PRODUCED GLOBALLY FROM THE SHELLS OF SHRIMP, CRAB,
LOBSTER, AND SQUID
• PRODUCTION OF CHITIN FROM MARINE SOURCES ARE
IDENTIFIED IN THE COUNTRIES SUCH AS INDIA, CHINA, JAPAN,
POLAND, AUSTRALIA, THE UNITED STATES AND NORWAY
4. CHITOSAN EXTRACTION
• THE PRODUCTION OF CHITOSAN STARTS WITH THE SELECTION
OF A SUITABLE SOURCE FOR CHITIN EXTRACTION. CHITIN CAN BE
EXTRACTED FROM EITHER THE ANIMAL SOURCES SUCH AS
SHELLFISH OR NON-ANIMAL SOURCES SUCH AS FUNGI. THE
PHYSICOCHEMICAL PROPERTIES OF CHITOSAN CAN VARY GREATLY
DEPENDING ON ITS SOURCE.
• CHITIN IS EXTRACTED FROM NATURAL SOURCES VIA DE-
MINERALIZATION AND DE-PROTEINATION. THE PURIFIED CHITIN IS
THEN TREATED WITH CONCENTRATED ALKALIS (E.G. SODIUM
HYDROXIDE) TO OBTAIN CHITOSAN.
• THE PROCESS IS KNOWN AS DE-ACETYLATION AND IT AFFECTS
THE FINAL PROPERTIES OF CHITOSAN SUCH AS THE EXTENT OF
POSITIVE CHARGE (PROPORTION OF AMINE GROUPS IN POLYMER)
AND MOLECULAR WEIGHT.
6. PROCESSING OF
CHITOSAN
• CHITOSAN IS AN EXTREMELY
VERSATILE BIOMATERIAL. IT CAN
BE PROCESSED INTO VARIOUS
FORMS SUCH AS MICRO OR
NANO FIBERS, MICRO OR NANO
GELS, BEADS, FILMS OR
CAPSULES, SPONGES OR
SCAFFOLDS, MICRO OR
NANOPARTICLES, HYDROGEL
AND GAUZES.
7. SIGNIFICANCE OF DDA IN
CHITOSAN
• CHEMICALLY, CHITOSAN IS A DERIVATIVE OF CHITIN,
CONSISTING OF GLUCOSAMINE AND N-ACETYLGLUCOSAMINE
CHAINS, AND IS DERIVED MAINLY FROM THE ENDOSKELETON OF
CEPHALOPODS, EXOSKELETON OF ARTHROPODS AND CELL
MEMBRANE OF FUNGI AND PLANTS.
• REMOVAL OF ACETYL GROUPS FROM CHITIN IS DESCRIBED AS
THE PROCESS OF DE-ACETYLATION. DEGREE OF DE-ACETYLATION
EVALUATES THE CONTENT OF FREE AMINO GROUPS IN THE
MOLECULAR STRUCTURE OF CHITOSAN.
• WHEN THE NUMBER OF ACETAMIDE GROUPS OR DEGREE OF DE-
ACETYLATION IS MORE THAN 50% (IDEALLY 70-90 %) THE
POLYMER CONSIDERED AS A CHITOSAN MOLECULE. SO, IT PLAYS
AN IMPORTANT ROLE IN DIFFERENTIATING BETWEEN CHITOSAN
AND CHITIN.
8. DDA MEASUREMENT
TECHNIQUES FOR CHITOSAN
• NUCLEAR MAGNETIC
RESONANCE SPECTROSCOPY
• UV VISIBLE & INFRARED
SPECTROSCOPY
• POTENTIOMETRIC &
CONDUCTOMETRIC TITRATION
• DIFFERENTIAL SCANNING
CALORIMETRY
IMPACT OF DDA ON CHITOSAN
DDA IS CONSIDERED A KEY FACTOR
FOR CHITOSAN MOLECULE AS IT
STRONGLY INFLUENCES THE
BIOLOGICAL AND PHYSICOCHEMICAL
PROPERTIES. IT IMPACTS:
SOLUBILITY & CRYSTALLINITY
MOLECULAR WEIGHT & MOISTURE
CONTENT
CELLULAR RESPONSES AND
CELLULAR ADHESION
CELL AGGREGATION & SORPTION
PROPERTIES
HAEMOSTATIC AND WOUND HEALING
PROPERTIES
VISCOSITY & BIODEGRADABILITY
FACTORS AFFECTING THE
VISCOSITY OF CHITOSAN
MOLECULAR WEIGHT
POLYDISPERSITY INDEX
PRESENCE OF ELECTROLYTE &
TYPES OF SOLVENT
HUMIDITY & TEMPERATURE
PATTERN & DEGREE OF
DEACETYLATION
SOURCE & METHOD OF
PREPARATION
STERILIZATION, SHARE RATE &
CONCENTRATION VISCOSITY OF
CHITOSAN
THE INTRINSIC VISCOSITY OF 1%
CHITOSAN VARIES FROM 40 TO 5000
CPS DEPENDING ON SEVERAL
FACTORS.
9. PROPERTIES OF CHITOSAN
• CHITOSAN HAS BEEN EXTENSIVELY STUDIED AS A
BIOMATERIAL FOR VARIOUS APPLICATIONS. SOME OF
ITS KEY PROPERTIES ARE LISTED IN THIS IMAGE. DUE
TO ITS BIODEGRADABLE AND BIOCOMPATIBLE NATURE,
CHITOSAN HAS BEEN USED IN BOTH EXTERNAL AS
WELL AS IMPLANTABLE MEDICAL DEVICES.
• AS A FAT BINDER, IT HAS BEEN USED AS A WEIGHT-
LOSS AGENT. THE MUCOADHESIVE AND VISCOSITY
MODIFYING PROPERTIES MAKE IT USEFUL FOR DRUG
DELIVERY. THE HEMOSTATIC, ANTI-MICROBIAL, ANTI-
INFLAMMATORY, AND ANALGESIC PROPERTIES MAKE IT
AN EXCELLENT WOUND MANAGEMENT MATERIAL.
10. MECHANISM
S OF
IMPORTANT
PROPERTIES
OF
CHITOSAN
PROPERTY MECHANISM
Hemostasis Cationic chitosan binds to negatively charged blood cells and leads to
platelet activation.
Anti-microbial Positively charged chitosan molecules bind to negatively charged
microbial cell membranes, which leads to the disruption of microbial
membrane, and subsequently the leakage of proteinaceous and other
intracellular constituents.
Pain control Chitosan relieves pain through its analgesic effect by reducing
concentration of inflammatory mediators (bradykinin) at site of injury.
It also absorbs of proton ions released in the inflammatory site to
control pain.
Wound healing Chitosan helps in wound healing through multiple pathways such as,
polymorphonuclear cell activation, Fibroblast activation, Cytokine
production, Giant cell migration and Stimulation Of type IV collagen
synthesis.
Scar prevention Chitosan reduces the production of TNF-ß1&2, which are responsible
for scarring. Collagen produced in presence of chitosan is fine
reticulin-like fibrils rather than mature bands of dense collagen.
11. APPLICATIONS OF CHITOSAN
WOUND CARE
•HAEMOSTATIC ACTION OF CHITOSAN IS BASED ON THE RAPID
ABSORPTION OF BLOOD PLASMA THAT LEADS
CONCENTRATION OF ERYTHROCYTES AND PLATELET AT
INJURED PLACE, FOLLOWED BY PLATELET ACTIVATION AND
ERYTHROCYTE COAGULATION
•CHITOSAN PROMOTES RE EPITHELIZATION BY STIMULATING
THE PROLIFERATION OF DERMAL FIBROBLAST AND INHIBITING
THE PROLIFERATION OF KERATINOCYTES
•CHITOSAN ACT AS AN ANTIMICROBIAL AGENT BY CAUSING
THE LEAKAGE OF BACTERIAL CELL WALL THROUGH CHARGE-
BASED INTERACTION AND INHIBITION OF MRNA AND PROTEIN
SYNTHESIS AT BACTERIAL NUCLEI
•ANALGESIC EFFECT OF CHITOSAN COMES FROM THE
ABSORPTION OF BRADYKININ AND PROTON IONS AT
INFLAMMATORY SITE FOLLOWED BY BLOCKING OF
ARACHIDONIC PATHWAY BY PHOSPHOLIPASEA2 INHIBITION
•CHITOSAN PLAYS AN IMPORTANT ROLE FOR ANTI-
INFLAMMATORY ACTION BY PRODUCE SIGNIFICANT INHIBITION
EFFECT AGAINST INFLAMMATION MEDIATOR SUCH AS
INTERLEUKIN (IL)- 2, IL-4, IL-6, IL-10 AND IL-13, CYTOKINES SUCH
AS TNF-Α, NF-KΒ EXPRESSION AND AP-1 ACTIVATION
•CHITOSAN PROTECTS THE DIGESTION OF SKIN
EXTRACELLULAR MATRIX BY BLOCKING THE MATRIX
METALLOPROTEINASE-2 EXPRESSION
COSMETICS
•
CHITOSAN PROTECTS THE SKIN FROM THE EXPOSURE
OF UV RADIATION AND ACT AS A SUN SCREENING
AGENT ( SUN PROTECTOR FACTOR AROUND 0.89)
•CHITOSAN ACT AS A CATIONIC HUMECTANT THAT CAN
EASILY ABSORBED TO THE NEGATIVELY CHARGED SKIN
SURFACE AND HOLD THE MOISTURE CONTENT OF SKIN.
MOISTURE ABSORPTION CAPACITY ENHANCES WITH
THE INCREASE OF DEGREE OF DEACETYLATION OF
CHITOSAN
•POLYCATIONIC NATURE OF CHITOSAN HELPS TO
INTERACT WITH POLYANIONIC KERATIN THAT CAUSE
EASY FILM FORMATION AROUND HAIR FIBERS. THIS FILM
IMPROVES HAIR STRENGTH ,HAIR SOFTNESS, AND
AVOID HAIR DAMAGE.
•OPTIMUM PKA VALUE TO INHIBIT THE DENTAL PLAQUE
FORMATION AROUND 6.3 AND THIS VALUE COMES IN
THE RANGE OF CHITOSAN PKA VALUE (5.1-6.5)
•CHITOSAN HAS AN ABILITY TO BIND WITH ENAMEL TO
CREATE A PROTECTIVE LAYER THAT CAUSE REDUCTION
OF DENTAL ABRASION
PHARMACEUTICALS
•CHITOSAN HAS BEEN EXPLOITED
ESPECIALLY AS AN EXCIPIENT IN
PHARMACEUTICAL FORMULATION. DUE TO
ITS HYDROPHILIC NATURE IT CAN BE USED AS
DISINTEGRATING AND BINDER AGENT FOR
TABLET DOSAGE FORM
•GEL FORMING CAPABILITY OF CHITOSAN
BASED POLYMERIC MATRIX HELPS IN
CONTROL AND SUSTAINED DRUG DELIVERY
•POSITIVELY CHARGED CHITOSAN EASILY
BIND WITH FREE FATTY ACID AND BLOCK THE
ABSORPTION OF LIPID IN THE GUT. CHITOSAN
ALSO EMULSIFY THE FAT AND DISRUPTS THE
LIPID ABSORPTION IN THE INTESTINE
•HIGH MOLECULAR WEIGHT OF CHITOSAN
AND PRESENCE OF AMINO AND HYDROXY
GROUP MAKES IT SUITABLE FOR
PHARMACEUTICAL EXCIPIENT AS THICKENING
AGENT , SURFACTANT, EMULSIFIER ETC.