Nanoliposomes to the long-range mutual repulsion between adjacent bilayers.

Nanoliposomes have ability to approach
merely the precise cells, which is a prime requisite to accomplish preferred
drug concentration at the target position so that the adverse effects can be
minimized and optimum therapeutic efficacy on healthy cells and tissues can be
achieved. They can also to protect the active moiety in systemic circulation
and deliver it to the desired site of action at a sustained rate 14. Thus,
nanoliposomes as a carrier helped in improving the therapeutic index of drugs
by selective and controlled drug
delivery, by declining
the exposure of toxic drugs to sensitive tissue, and by controlling the drug
pharmacokinetics and biodistribution. All categories of drugs like hydrophobic,
amphipathic and hydrophilic drugs are suitably delivered by using nanoliposomes
as a carrier as it carried both lipophilic and hydrophilic environment in one
system (27-29). Moreover, nanoliposomes have found imminent applications in the
various fields of nanotechnology like gene delivery, cancer therapy, agriculture,
food technology, diagnosis, and cosmetics. High production cost, oxidation and
hydrolysis of phospholipids, seepage and blending of encapsulated
drug/molecules, less stability, small half-life, and squat solubility are some
of the limitations of nanoliposomes. However, the stability problem of
nanoliposomes in vitro and in vivo limits their application. The nanoliposomes
have tendency to aggregate or degrade and fuse, which causes leakage of core
material during storage and clears rapidly from the system after intravenous
injection. Literature suggested that, among various factors that affect the
stability of nanoliposomes, carrier’s surface characteristics like charge,
lipophilicity, and fluidity, are of great importance. Therefore, the little
modification of carrier’s surface by using polymers with desired properties, we
can easily modulate there in vitro
and in vivo stability.

Polymer coating is a pledging way
of amending the surface characteristics of nanoliposomes, in which the
nanoliposomes suspension was mixed with a polymer solution simply without any
chemical linking of polymers to the lipid molecules. Polymer coating improved
the stability of nanoliposomes during storage due to the long-range mutual
repulsion between adjacent bilayers. Various natural polymers like polysaccharides
and synthetic polymers like polyethylene, polyvinyl alcohol, or polyacrylamide
have been used to modify the surface characterstics and to increase the
stability of nanoliposomes.  Among which
chitosan is a positively charged polysaccharide and can be used to increase and
modify the characteristics of nanoformulations, is found to have a promising
future in the medical and pharmaceutical fields.

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Chitosan, a polycationic polymer due
to existence of amino groups comprised mainly of glucosamine units. It is
N-deacetylated derivative of chitin having antioxidant and anti-in?ammatory
properties Qiao
et al., 2011, Cao et al., 2016.
Tissue engineering, obesity control and drug development are its several promising
applications. During new drug formulation it used most widely as being biocompatible
and biodegradable it also provide a protective capsule like shield to drug
molecule Mady and
Darwish, 2010. Its chemical
configuration and various suitable features like abundance, hydrophobicity,
antimicrobial activity, low toxicity, biocompatibility, and biodegradability made
chitosan an important ingredient to be used in the preparation various modified
formulation and carriers like microsphere, microfilme, nanoparticles, films,
gels. As a carrier to entrapped and release active ingredient, it found
applications in various fields like cosmetics, pharmaceuticals, food and
biotechnology. Literature suggested that various authors have used chitosan or related
polymers as a coating material for liposomes, nanoliposomes for targeting
purposes and to increase their stability towards drug release Dong and Rogers, 1991. We recognized that suitable
combination of the polymer based and lipid-based systems could amalgamate the
advantages and diminish the disadvantages of each system, and thus lead to development
of new system carrying advantages of both systems Dai et al., 2006.

In the present work,
nanoliposomes were prepared by using reverse-phase evaporation (REV) method and
modified emulsification and ultrasonication (MEU) method and then, both the
preparations were coated with different concentrations of chitosan solutions.
Then, the effects of different concentration of chitosan solution on particle
size, zeta potential and in vitro drug release rate were studied. The transmission
electron microscopy, FTIR studes, DSC analysis, particle size and zeta
potential studies were used to investigate presence of chitosan coating on
nanoliposomes. The characteristics of uncoated and chitosan-coated
nanoliposomes were studied to develop and further optimize nanoliposomes that
are directed for their systemic pharmacological applications.Nanoliposomes were prepared by reverse-phase
evaporation (REV) method and modified emulsification and ultrasonication (MEU) method.
In reverse-phase evaporation method, soya lecthin and cholestrol were dissolved
in diethyl ether and gefitinib was dissolved in distilled water. The mixing of
organic phase and aqueous phase was done in ratio (3:1, v/v), and a lipid film
was formed under reduced pressure at 40 ?C, using a rotary evaporator. Then 10
ml phosphate buffer solution (0.10 M, pH 7.0, PBS) containing Tween 80 was added
under a stream of nitrogen. Nanoliposomes were obtained by reducing the size of
nanoliposomes using ultrasonication with a probe sonicator in an ice bath with
1s ON, 1s OFF intervals, for a total period of 10 min Ding et al., 2011.

In modified emulsification and ultrasonication
method, gefitinib was dissolved in anhydrous ethanol to obtain a desired
concentration of gefitinib ethanolic solution. The ethanolic solution of
gefitinib containing lipid phase was heated on a water bath at 60 ?C. Tween 80
was dissolved in 10ml of phosphate buffer of pH 6.8 and maintained at 60 ?C as
the aqueous phase. The aqueous phase was dropped into the non-aqueous phase
under magnetic stirring. The consequential preparation was stirred for another
10 min, and then ultrasonication was done. Then, the preparation placed on an
ice bath and diluted to a desired volume. Finally the preparation was filtered
through a 0.22µm membrane filter Guan et al., 2011.

 

Both the preparations were
centrifuged seperately. The formed pellet was washed with sterile double
distilled deionised water and re-centrifuged; this step was repeated four times
and the pellet then re-suspended in an appropriate amount of sterile double
distilled deionised water.

For chitosan-coated nanoliposomes,
an appropriate amount of percentage (w/v) chitosan solution was added drop wise
to the nanoliposomal suspension under magnetic stirring at room temperature.
After addition of chitosan, the mixture was left to stir for approximately 1 h
and then incubated overnight at 4 ?C Mady and Darwish, 2010, Shin et al.,
2013.