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MUCOADHESIVE IN SITU GELS: A NOVEL NASAL DRUG DELIVERY SYSTEM
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.)
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
• 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
Fig:1 Parts of nasal cavity consists of nasal
vestibule, inferior turbinate, middle
turbinate, superior turbinate & Olfactory
• Results in higher bioavailability thus use lower doses of
• Results in rapid absorption and onset of action.
• Easily accessible, non-invasive route.
• Avoids degradation of drug in GIT resulting from acidic or
• 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
• The absorption here is slow.
• It is also known as the
• It involves a lipoidal route of
• 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
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
• Mechanism of mucoadhesion are
of two steps :
Interaction with Mucus
Hydration & Swelling of Polymers
Hydrophilic Macromolecular Drug
Ciliary Clearance Enzymatic Metabolism
• Gel is the state which exists between solid and liquid
• 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 gel
In situ gel
A. Thermally triggered
• Three main strategies exist for thermally triggered system :
• Negatively thermo-sensitive have lower critical solution
• positively thermo-sensitive have upper critical solution
• 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
• 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/
• 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
3. Viscosity and rheology.
4. Evaluation of the mucoadhesive strength.
5. In vitro drug diffusion.
6. In vitro permeation studies.
• Lectins are carbohydrate-binding
that are highly specific for
• 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
• This increases the
viscosity of the
residence time of the
3. Alginate Poly-Ethylene Glycol Acrylate
• Alginate-PEGA has an
alginate backbone with
groups attached to it.
• It is known to undergo ionic
sol to gel transition
(gelation) upon interaction
with multivalent ions such as
• Combining these three
functional moieties of
glycol Acrylate leads to
an improved novel
polymer which can be
nasal drug delivery.
4. Poloxamer (Pluronics)
• Poloxamers are made non-ionic difunctional triblock
copolymers containing a centrally located hydrophobic
polypropylene oxide between hydrophilic polyethylene
• 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
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
2. Bacterial Adhesion
• The attachment of
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
present to these glycoproteins.
• In certain disease conditions the
sequence of glycoproteins is
• This altered state can be used as
a target by complementary
amino acid sequences by
attaching them to a drug delivery
4. Antibody mechanism
• Antibodies can be a rational
choice as a polymeric ligand for
mucoadhesives due to their
• 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,
• Utkarshini Anand, Tiam Feridooni and Remigius U. Agu,
Novel Mucoadhesive Polymers for Nasal Drug
• 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,