Research Article
Significance of Algal Polymer in Designing
Amphotericin B Nanoparticles
Saurabh Bhatia,
1
Vikash Kumar,
1
Kiran Sharma,
2
Kalpana Nagpal,
3
and Tanmoy Bera
4
1
PDMCOP, Bahadurgarh, Haryana 124507, India
2
Department of Pharmaceutical Sciences, Jamia Hamdard, New Delhi 110062, India
3
School of Pharmacy, Faculty of Applied Medical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
4
Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
Correspondence should be addressed to Saurabh Bhatia; sbsaurabhbhatia@gmail.com
Received 7 July 2014; Revised 1 September 2014; Accepted 15 September 2014; Published 12 November 2014
Academic Editor: Rizwan Hasan Khan
Copyright © 2014 Saurabh Bhatia et al. his is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Development of oral amphotericin B (AmB) loaded nanoparticles (NPs) demands a novel technique which reduces its toxicity and
other associated problems. Packing of AmB in between two oppositely charged ions by polyelectrolyte complexation technique
proved to be a successful strategy. We have developed a novel carrier system in form of polyelectrolyte complex of AmB by using
chitosan (CS) and porphyran (POR) as two oppositely charged polymers with TPP as a crosslinking agent. Initially POR was
isolated from Porphyra vietnamensis followed by the fact that its alkali induced safe reduction in molecular weight was achieved.
Formulation was optimized using three-factor three-level (3
3
) central composite design. High concentration of POR in NPs was
conirmed by sulfated polysaccharide (SP) assay. Degradation and dissolution studies suggested the stability of NPs over wide pH
range. Hemolytic toxicity data suggested the safety of prepared formulation. In vivo and in vitro antifungal activity demonstrated the
high antifungal potential of optimized formulation when compared with standard drug and marketed formulations. hroughout
the study TPP addition did not cause any signiicant changes. herefore, these experimental oral NPs may represent an interesting
carrier system for the delivery of AmB.
1. Introduction
Increasing prevalence of serious systemic infections such
as aspergillosis, candidiasis, and cryptococcosis demands a
potent fungicidal agent that efectively destroys the fungal
growth without the development of any resistance and tox-
icity. Amphotericin B (AmB) is a broad-spectrum polyene
macrolide antifungal agent that does not induce resistance, is
widely known for the treatment of life-threatening systemic
fungal infections, and acts as second line drug of choice for
visceral leishmaniasis [1–4]. However its poor water solubil-
ity, poor stability (in acidic pH), low intestinal permeability,
and various dose related serious side efects, for example,
nephro and hemolytic toxicity, limit its therapeutic eicacy
in oral drug delivery system [5]. All these problems are
associated with diferent states of AmB in aqueous media
which determines the overall activity of drug [5]. hat
is why it is conventionally administrated parenterally. We
have efort fully established a clear relationship between the
solubility, antifungal activity, and its related toxicities (Figure
1). Nanoparticulate delivery system is the most suitable mode
for delivering AmB. Most of the currently available AmB
nanoformulations are lipid based (Ambisome, Amphocil, and
Abelcet) though some are also available in micellar (Fungi-
zone) and nanosuspension form [2]. hese all formulations
have their serious concerns such as rapid release, surfactant
related toxicities, low drug loading capacity, diicult route of
administration, limited in vivo eicacy, and high price [2].
hus there is an urgent need for efective oral antifungal drug
delivery system that not only reduces the side efects but also
increases the absorption of AmB in a controlled manner.
PEC technique for nanoparticles involves the controlled
mixing of diluted polycation and polyanion solutions that
gives the size range of 20 to 500 nm with various shapes
such as spherical, toroid, and rod-like shapes or have a loose
gel-like shape up to compact internal structure. hey are
Hindawi Publishing Corporation
e Scientific World Journal
Volume 2014, Article ID 564573, 21 pages
http://dx.doi.org/10.1155/2014/564573