ABSTRACT
Metformin loaded silver nanoparticles were synthesized using ecofriendly method with
extract of Azadiractha indica as reducing agent and two natural polymers; guar gum and
xanthan gum, Sodium alginate, and a semi- synthetic polymer (AMS) as stabilizing agents.
Twelve batches of nanoparticles were synthesized. Nanocomposites synthesized from AMS
were designated as AMS 1% NANOmet, AMS3% NANOmet and AMS5% NANOmet. Guar
gum stabilized nanoparticles were designated as GG1% NANOmet, GG3% NANOmet and
GG5% NANOmet while Xanthan gum nanocomposites were coded as XG1% NANOmet,
XG3% NANOmet and XG5% NANOmet respectively. Sodium alginate stabilized
nanocomposites were designated as NaALG1% NANOmet, NaALG3% NANOmet and
NaALG5% NANOmet respectively. The percentage yield of nanocomposites was high with
values ranging from 80 % to 99.87 %. The entrapment efficiencies of the samples ranged
from 63.06 % to 80.22 % while the loading capacities were in the range of 7.24 % to 24.10
%. Differential scanning calorimetry showed there was no interaction between the polymers
and metformin. Characterization of the metformin nanocomposites using UV- vis
spectroscopy, zeta sizer, scanning electron microscopy (SEM) and polydispersity were
performed. The UV-vis spectroscopy showed surface plasmon resonance of 371nm for all the
nanocomposites except XG5%NANOmet which had SPR of 335nm. The mean particle size
of GG1%NANOmet was ideal with a value of 188.7nm followed by AMS1%NANOmet
(386.7 nm). All the batches showed extended and sustained release profile with initial burst
effect at the first 30 min of release studies. Release of metformin in SIF was predominantly
higher than in SGF. The kinetics of release was mainly zero order for all the nanocomposites
with the exception of NaALG5% NANOmet which released the drug by higuchi kinetics.
Antimicrobial property of the optimized nanocomposites were similar (P>0.05). Generally,
MIC values of the samples against the microorganisms tested ranged from 2500- 5000μg/ml.
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In vivo anti hyperglycemic property of the optimized metformin nanocomposite using
glucose hyperload model results showed GG5%NANOmet as the optimum batch. At equal
doses it produced sustained and consistent significant (p<0.001) decrease in elevated blood
glucose level in glucose loaded hyperglycemic rats when compared with metformin and other
nanocomposites treated groups.
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CHAPTER ONE
1.0. INTRODUCTION
In recent years, there has been an exponential interest in the development of novel
drug delivery systems using nanoparticles [1]. The transition from microparticles to
nanoparticles has led to a number of changes in physical properties of materials [2]. Two of the
major factors in this are the increase in the ratio of surface area to volume, and the size of the
particle moving into the realm quantum effects predominate. The increase in the surface-area-tovolume
ratio, which is a gradual progression as the particle gets smaller, leads to an increasing
dominance of the behaviour of atoms on the surface of the particle over that of those in the
interior of the particle. This affects both the properties of the particle in isolation and its
interaction with other material. [2]
There have been tremendous developments in the field of Nanotechnology in recent
time with various technologies formulated to synthesize nanoparticles with specific
characteristics on morphology and distribution [3]. Although, there are several methods for
the synthesis of nanoparticles, they are very expensive and involve the use of toxic and
hazardous chemicals which cause danger to humans and the environment [4]. To overcome
these challenges, the eco-friendly synthesis of nanoparticles using environmentally benign
materials like Plants [5], microorganisms [4,5], seaweed [6] and enzymes [7] were employed.
It is a single step and offers several advantages such as time reducing, cost effective and Nontoxic.
Nanocrystalline silver is a known Noble metal and they have tremendous applications
in the field of Detection, Diagnostics, Therapeutics and Antimicrobial activity [8].
In general, nanoparticles offer significant advantages over the conventional drug delivery in
terms of high stability, high specificity, high drug carrying capacity, ability for controlled
release, possibility to use in different route of administration and the capability to deliver
both hydrophilic and hydrophobic drug molecules.