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The Project Presentation is submitted to 
BCDA COLLEGE OF PHARMACY AND TECHNOLOGY 
Under the guidance of 
Mr. Seemanchala Rath, Assistant Professor 
M. Pharm. (Utkal Univ.) 
By 
Nilanjan Bhattacharya B. Pharm. 7th Sem. 
University Roll No : 20101911022 
& 
Prosenjit Chakraborty B. Pharm. 7th Sem. 
University Roll No : 20101911026
• The use of nasal cavity as a route of administration of 
drugs, specifically systemically acting drugs that pose a 
delivery challenge, have become an area of great 
interest. 
• In situ forming polymeric formulations are drug 
delivery systems that are in sol form before 
administration in the nasal cavity, but once 
administered, undergo gelation in situ, to form a gel. 
• This presentation will gives us an overview of how 
mucoadhesive in situ gels as a promising approach for 
nasal drug delivery system.
Fig:2 Cell types of the nasal epithelium 
showing ciliated cell (A), non-ciliated cell(B), 
goblet cells(C), gel mucus layer (D), sol layer 
(E), basal cell (F) and basement membrane 
(G) 
Fig:1 Parts of nasal cavity consists of nasal 
vestibule, inferior turbinate, middle 
turbinate, superior turbinate & Olfactory 
neurons.
• Results in higher bioavailability thus use lower doses of 
drug. 
• Results in rapid absorption and onset of action. 
• Easily accessible, non-invasive route. 
• Avoids degradation of drug in GIT resulting from acidic or 
enzymatic degradation. 
• High molecular weight compounds cannot be 
delivered through this route. 
• Volume that can be delivered into nasal cavity is 
restricted to 25 –200 μl.
• It involves an aqueous route of 
transportation. 
• The absorption here is slow. 
• It is also known as the 
paracellular route. 
First 
Mechanism 
• It involves a lipoidal route of 
transportation. 
• Drug cross cell membranes by an 
active transport route via carrier-mediated 
means or transport through 
the opening of tight junctions. 
• It is also known as the transcellular 
process. 
Second 
Mechanism
Mucoadhesion is a state in which two materials, one of which is 
biological in nature, are maintained together for a prolonged time 
period by means of interfacial forces. 
• The mucoadhesives spread over 
the substrate to initiate close 
contact & increase surface 
contact, promoting the diffusion 
of its chains within the mucus. 
• Attraction and repulsion forces 
arises for a mucoadhesive to be 
successful. 
• Mechanism of mucoadhesion are 
of two steps : 
 Contact stage 
 Consolidation stage
Mucoadhesive Carrier 
Interaction with Mucus 
Hydration & Swelling of Polymers 
Drug Release 
Hydrophilic Macromolecular Drug 
Ciliary Clearance Enzymatic Metabolism 
Internal Absorption
Gels 
• Gel is the state which exists between solid and liquid 
phase. 
• The solid component comprises a three dimensional 
network of inter-linked molecules. 
In-Situ Gel Delivery System 
• It is a process of gel formation at the site of action 
after the formulation has been applied at the site. 
• The phenomenon based upon liquid solution of 
drug formulation and converted into semi-solid 
mucoadhesive key depot.
• Increased residence time of drug in nasal cavity. 
• Low dose required. 
• Results in rapid absorption and onset of effect. 
• The nasal in-situ gel follows phase transition 
mechanism and to stand with the shear forces in the 
nasal cavity wall. 
• Nasal in-situ gel should have long residence time. 
• It should be of low viscosity.
They can be classified under: 
IN SITU 
FORMING 
HYDROGELS 
In situ gel 
formation based 
on physiological 
stimuli 
Thermally 
triggered 
pH triggered 
In situ gel 
formation based 
on chemical 
reactions 
Ionic cross 
linking 
Photo-polymerization
A. Thermally triggered 
• Three main strategies exist for thermally triggered system : 
• Negatively thermo-sensitive have lower critical solution 
temperature (LCST). 
• positively thermo-sensitive have upper critical solution 
temperature (UCST). 
• Thermo-reversible gels are made from Pluronics. 
• All the pH-sensitive formations contain acidic or basic 
groups that either accept or release protons which is 
triggered by the change in environmental pH.
A. Ionic Cross-linking 
• Polymers may undergo phase transition in presence of 
various ions 
• k-carrageenan forms rigid, brittle gels in replacement of 
small amount of K+ while i-carrageenan forms elastic gels 
mainly in the presence of Ca2+ ion. 
• Alginic acid undergoes gelation in presence of divalent/ 
polyvalent cations. 
• A solution of monomers or reactive macromers and 
initiator can be injected into a tissue site and an 
electromagnetic radiation used to form gel. 
• Acrylate or similar functional groups undergo photo-polymerization 
in the presence of suitable photo initiator.
1. Measurement of gelation temperature and gel 
melting. 
2. Gel-strength. 
3. Viscosity and rheology. 
4. Evaluation of the mucoadhesive strength. 
5. In vitro drug diffusion. 
6. In vitro permeation studies.
1. Lectins 
• Lectins are carbohydrate-binding 
proteins, macromolecules 
that are highly specific for 
sugar moieties. 
• Lectins have the ability to stay on 
the cell surface . 
• Lectins allow target specific 
attachment & also act as a means 
of delivering the drug through a 
controlled process to the cells .
• Thiomers are mucoadhesive 
polymers having side chains 
carrying thiol which lead to 
formation of covalent bonds 
between the cystiene groups in 
the mucus and the polymer by 
simple oxidation process. 
• Thiolated polymers display in situ 
gelling properties due to the 
oxidation of thiol groups at 
physiological pH-values resulting in 
the formation of intermolecular 
and intramolecular disulfide 
bonds. 
• This increases the 
viscosity of the 
formulation thereby 
increasing the 
residence time of the 
product tremendously. 
2. Thiomers
3. Alginate Poly-Ethylene Glycol Acrylate 
• Alginate-PEGA has an 
alginate backbone with 
acrylated polyethylenglycol 
groups attached to it. 
• It is known to undergo ionic 
sol to gel transition 
(gelation) upon interaction 
with multivalent ions such as 
Ca2+, Fe2+. 
• Combining these three 
functional moieties of 
Alginate Polyethylene 
glycol Acrylate leads to 
an improved novel 
polymer which can be 
used mucoadhesive 
nasal drug delivery.
4. Poloxamer (Pluronics) 
• Poloxamers are made non-ionic difunctional triblock 
copolymers containing a centrally located hydrophobic 
polypropylene oxide between hydrophilic polyethylene 
oxides. 
• Poloxamers have thermoreversible property which 
convert from a liquid to a gel at body temperature, 
thus, causing in situ gelation at the site of interest. 
• Poloxamers are also known as Pluronics. 
• Pluronics have been chemically combined with poly 
(acrylic acids) to produce systems with enhanced 
adhesion and retention in the nasal cavity. E.g.: 
Poloxamer 407 (Pluronic F127) .
1. Mucoadhesive Nanoparticles 
• Mucoadhesive nanoparticles 
offers better encapsulation 
efficiency, enhanced 
biocompatibility control release & 
has less toxic properties. 
• Polymeric mucoadhesive NP with 
improved sinus mucus 
penetration capability which may 
lead to the development of new 
generations of nanoparticle based 
intranasal drug delivery 
systems.
2. Bacterial Adhesion 
• The attachment of 
synthetic/natural macromolecules 
to mucus or epithelial surface is 
defined as bioadhesion. 
• Bacteria are capable of adhering to 
the epithelium surface with aid of 
fimbriae, which are long, lectin-like 
proteins found on the surface 
of many bacterial strains. 
• The adhesion of bacteria to 
epithelial surfaces is used as an 
efficient method for nasal drug 
delivery with the intention of 
reducing mucociliary clearance.
3. Altered Amino Acid Sequence 
• Certain amino acid sequences 
can be used to promote binding 
of drug molecules to specific cell 
surface glycoproteins due to the 
amino acids having 
complementary sequences 
present to these glycoproteins. 
• In certain disease conditions the 
sequence of glycoproteins is 
altered. 
• This altered state can be used as 
a target by complementary 
amino acid sequences by 
attaching them to a drug delivery 
device.
4. Antibody mechanism 
• Antibodies can be a rational 
choice as a polymeric ligand for 
designing site-specific 
mucoadhesives due to their 
high specificity. 
• Antibodies can be produced 
against selected molecules 
present on mucosal surfaces. 
• This approach can be useful for 
targeting drugs to tumor tissues 
or even normal cells.
There is no question that the nasal route has a great 
potential for systemic drug delivery. . As nose- to- brain 
delivery makes it possible to by-pass the blood-brain 
barrier for certain drugs; administration of drugs via 
this route for treatment of neurological diseases 
presents exciting opportunities. Several strategies have 
been developed to enable the drug molecules to attach 
onto the mucus or epithelial layer, thus preventing 
them from being cleared from the nasal cavity. The 
application of lectins, thiomers, alginate poly-ethylene 
glycol acrylate and poloxamers have been of great use 
to overcome the challenges.
• Singh S, Kanupriya and kumar S.L.H, INTRANASAL 
THERMOREVERSIBLE MUCOADHESIVE GELS: A 
Review, International Journal of Pharmacy, 2012; vol:2, 
Issue-3. 
• Utkarshini Anand, Tiam Feridooni and Remigius U. Agu, 
Novel Mucoadhesive Polymers for Nasal Drug 
Delivery,INTECH. (http://dx.doi.org/10.5772/52560) 
• Alagusundaram M*, Chengaiah B, Gnanaprakash K, 
Ramkanth S, Chetty CM, Dhachinamoorthi D, Nasal drug 
delivery system - An overview, International Journal of 
Research in Pharmaceutical Sciences, 2010 Vol-1, Issue-4, 
454-465.
MUCOADHESIVE IN SITU GELS: A NOVEL NASAL DRUG DELIVERY SYSTEM

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MUCOADHESIVE IN SITU GELS: A NOVEL NASAL DRUG DELIVERY SYSTEM

  • 1. The Project Presentation is submitted to BCDA COLLEGE OF PHARMACY AND TECHNOLOGY Under the guidance of Mr. Seemanchala Rath, Assistant Professor M. Pharm. (Utkal Univ.) By Nilanjan Bhattacharya B. Pharm. 7th Sem. University Roll No : 20101911022 & Prosenjit Chakraborty B. Pharm. 7th Sem. University Roll No : 20101911026
  • 2. • The use of nasal cavity as a route of administration of drugs, specifically systemically acting drugs that pose a delivery challenge, have become an area of great interest. • In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the nasal cavity, but once administered, undergo gelation in situ, to form a gel. • This presentation will gives us an overview of how mucoadhesive in situ gels as a promising approach for nasal drug delivery system.
  • 3. Fig:2 Cell types of the nasal epithelium showing ciliated cell (A), non-ciliated cell(B), goblet cells(C), gel mucus layer (D), sol layer (E), basal cell (F) and basement membrane (G) Fig:1 Parts of nasal cavity consists of nasal vestibule, inferior turbinate, middle turbinate, superior turbinate & Olfactory neurons.
  • 4. • Results in higher bioavailability thus use lower doses of drug. • Results in rapid absorption and onset of action. • Easily accessible, non-invasive route. • Avoids degradation of drug in GIT resulting from acidic or enzymatic degradation. • High molecular weight compounds cannot be delivered through this route. • Volume that can be delivered into nasal cavity is restricted to 25 –200 μl.
  • 5. • It involves an aqueous route of transportation. • The absorption here is slow. • It is also known as the paracellular route. First Mechanism • It involves a lipoidal route of transportation. • Drug cross cell membranes by an active transport route via carrier-mediated means or transport through the opening of tight junctions. • It is also known as the transcellular process. Second Mechanism
  • 6. Mucoadhesion is a state in which two materials, one of which is biological in nature, are maintained together for a prolonged time period by means of interfacial forces. • The mucoadhesives spread over the substrate to initiate close contact & increase surface contact, promoting the diffusion of its chains within the mucus. • Attraction and repulsion forces arises for a mucoadhesive to be successful. • Mechanism of mucoadhesion are of two steps :  Contact stage  Consolidation stage
  • 7. Mucoadhesive Carrier Interaction with Mucus Hydration & Swelling of Polymers Drug Release Hydrophilic Macromolecular Drug Ciliary Clearance Enzymatic Metabolism Internal Absorption
  • 8. Gels • Gel is the state which exists between solid and liquid phase. • The solid component comprises a three dimensional network of inter-linked molecules. In-Situ Gel Delivery System • It is a process of gel formation at the site of action after the formulation has been applied at the site. • The phenomenon based upon liquid solution of drug formulation and converted into semi-solid mucoadhesive key depot.
  • 9. • Increased residence time of drug in nasal cavity. • Low dose required. • Results in rapid absorption and onset of effect. • The nasal in-situ gel follows phase transition mechanism and to stand with the shear forces in the nasal cavity wall. • Nasal in-situ gel should have long residence time. • It should be of low viscosity.
  • 10. They can be classified under: IN SITU FORMING HYDROGELS In situ gel formation based on physiological stimuli Thermally triggered pH triggered In situ gel formation based on chemical reactions Ionic cross linking Photo-polymerization
  • 11. A. Thermally triggered • Three main strategies exist for thermally triggered system : • Negatively thermo-sensitive have lower critical solution temperature (LCST). • positively thermo-sensitive have upper critical solution temperature (UCST). • Thermo-reversible gels are made from Pluronics. • All the pH-sensitive formations contain acidic or basic groups that either accept or release protons which is triggered by the change in environmental pH.
  • 12. A. Ionic Cross-linking • Polymers may undergo phase transition in presence of various ions • k-carrageenan forms rigid, brittle gels in replacement of small amount of K+ while i-carrageenan forms elastic gels mainly in the presence of Ca2+ ion. • Alginic acid undergoes gelation in presence of divalent/ polyvalent cations. • A solution of monomers or reactive macromers and initiator can be injected into a tissue site and an electromagnetic radiation used to form gel. • Acrylate or similar functional groups undergo photo-polymerization in the presence of suitable photo initiator.
  • 13. 1. Measurement of gelation temperature and gel melting. 2. Gel-strength. 3. Viscosity and rheology. 4. Evaluation of the mucoadhesive strength. 5. In vitro drug diffusion. 6. In vitro permeation studies.
  • 14. 1. Lectins • Lectins are carbohydrate-binding proteins, macromolecules that are highly specific for sugar moieties. • Lectins have the ability to stay on the cell surface . • Lectins allow target specific attachment & also act as a means of delivering the drug through a controlled process to the cells .
  • 15. • Thiomers are mucoadhesive polymers having side chains carrying thiol which lead to formation of covalent bonds between the cystiene groups in the mucus and the polymer by simple oxidation process. • Thiolated polymers display in situ gelling properties due to the oxidation of thiol groups at physiological pH-values resulting in the formation of intermolecular and intramolecular disulfide bonds. • This increases the viscosity of the formulation thereby increasing the residence time of the product tremendously. 2. Thiomers
  • 16. 3. Alginate Poly-Ethylene Glycol Acrylate • Alginate-PEGA has an alginate backbone with acrylated polyethylenglycol groups attached to it. • It is known to undergo ionic sol to gel transition (gelation) upon interaction with multivalent ions such as Ca2+, Fe2+. • Combining these three functional moieties of Alginate Polyethylene glycol Acrylate leads to an improved novel polymer which can be used mucoadhesive nasal drug delivery.
  • 17. 4. Poloxamer (Pluronics) • Poloxamers are made non-ionic difunctional triblock copolymers containing a centrally located hydrophobic polypropylene oxide between hydrophilic polyethylene oxides. • Poloxamers have thermoreversible property which convert from a liquid to a gel at body temperature, thus, causing in situ gelation at the site of interest. • Poloxamers are also known as Pluronics. • Pluronics have been chemically combined with poly (acrylic acids) to produce systems with enhanced adhesion and retention in the nasal cavity. E.g.: Poloxamer 407 (Pluronic F127) .
  • 18. 1. Mucoadhesive Nanoparticles • Mucoadhesive nanoparticles offers better encapsulation efficiency, enhanced biocompatibility control release & has less toxic properties. • Polymeric mucoadhesive NP with improved sinus mucus penetration capability which may lead to the development of new generations of nanoparticle based intranasal drug delivery systems.
  • 19. 2. Bacterial Adhesion • The attachment of synthetic/natural macromolecules to mucus or epithelial surface is defined as bioadhesion. • Bacteria are capable of adhering to the epithelium surface with aid of fimbriae, which are long, lectin-like proteins found on the surface of many bacterial strains. • The adhesion of bacteria to epithelial surfaces is used as an efficient method for nasal drug delivery with the intention of reducing mucociliary clearance.
  • 20. 3. Altered Amino Acid Sequence • Certain amino acid sequences can be used to promote binding of drug molecules to specific cell surface glycoproteins due to the amino acids having complementary sequences present to these glycoproteins. • In certain disease conditions the sequence of glycoproteins is altered. • This altered state can be used as a target by complementary amino acid sequences by attaching them to a drug delivery device.
  • 21. 4. Antibody mechanism • Antibodies can be a rational choice as a polymeric ligand for designing site-specific mucoadhesives due to their high specificity. • Antibodies can be produced against selected molecules present on mucosal surfaces. • This approach can be useful for targeting drugs to tumor tissues or even normal cells.
  • 22. There is no question that the nasal route has a great potential for systemic drug delivery. . As nose- to- brain delivery makes it possible to by-pass the blood-brain barrier for certain drugs; administration of drugs via this route for treatment of neurological diseases presents exciting opportunities. Several strategies have been developed to enable the drug molecules to attach onto the mucus or epithelial layer, thus preventing them from being cleared from the nasal cavity. The application of lectins, thiomers, alginate poly-ethylene glycol acrylate and poloxamers have been of great use to overcome the challenges.
  • 23. • Singh S, Kanupriya and kumar S.L.H, INTRANASAL THERMOREVERSIBLE MUCOADHESIVE GELS: A Review, International Journal of Pharmacy, 2012; vol:2, Issue-3. • Utkarshini Anand, Tiam Feridooni and Remigius U. Agu, Novel Mucoadhesive Polymers for Nasal Drug Delivery,INTECH. (http://dx.doi.org/10.5772/52560) • Alagusundaram M*, Chengaiah B, Gnanaprakash K, Ramkanth S, Chetty CM, Dhachinamoorthi D, Nasal drug delivery system - An overview, International Journal of Research in Pharmaceutical Sciences, 2010 Vol-1, Issue-4, 454-465.