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Encapsulation of tomoxifen citrate by chitosan for oral delivery
Ravikumara Neralakere Ramannaa, Basavaraj Madhusudhanb*
a
b
Department of Biochemistry, P.G.Centre, Kuvempu University, Shivagangothri, Davangere -577 002, Karnataka, India.
Research Center for Nanoscience and Technology, Department of Biochemistry and Food Technology, Davangere University,
Shivagangothri, Davangere -577 002, Karnataka, India.
Email: [email protected]
Abstract
The objective of this study was to evaluate the characteristics of tamoxifen citrate-loaded chitosan
nanoparticles (tamoxcL-ChtNPs) and tamoxifen citrate-free chitosan nanoparticles (ChtNPs)
prepared by ionic gelation (IG) of chitosan with tripolyphosphate (TPP). These nanoparticles were
characterized by their degree of deacetylation (DD) in chitosan, particle size and zeta potential using
photon correlation spectroscopy (PCS) and Zeta PALS. Physicochemical properties of ChtNPs were
studied using SEM, FTIR and DSC. The compatibility of tamoxifen citrate-alone (tamoxcA) with
the TPP and chitosan was confirmed by FTIR and DSC studies. The variation in particle size and
encapsulation efficiency (EE) was assessed by changing the concentration of chitosan, TPP and the
pH of the solution. These nanoparticles had mean diameter of 187 nm, polydispersity of 0.125 and
zeta potential of +9 mV to +30 mV. At higher concentration of tamoxifen citrate (tamoxc) the EE
value was greater than that at lower one. Release of tamoxc from the chitosan matrix showed
biphasic pattern in a controlled manner. Drug release (DR) from tamoxcL-ChtNPs was studied at
physiological pH using phosphate buffer saline. From data, ChtNPs were found to be a good carrier
of tamoxc and release the cargo in a slow and sustained manner. The nanoparticles were found to be
non-toxic from haemocompatibility study will be discussed.
Keywords: Tamoxifen citrate; Chitosan; Ionic gelation; Encapsulation efficiency; Control release;
Haemocompatibility
Today, tamoxifen is the drug of choice for estrogen-mediated treatment among breast cancer
patients. The anti-estrogenic (breast) or estrogenic (uterus) activity of tamoxifen is known to be
dependent on the level of dose and location of tissue. Both agonistic and antagonistic properties of
tamoxifen are being exploited in the use of additional therapy soon after the primary treatment in
early stage of breast cancer. Apart from reported side effects, postmenopausal tamoxifen treatment
appears to be its proliferative effect on the endometrium in causing cancer and other related diseases.
According to de Lima et al. the use of tamoxifen at low dose (0.1 μM) generates oxidative stress and
induces either cell proliferation or apoptosis in dose dependant manner. Unfortunately, it has been
documented that dose dependant tamoxifen therapy would induce liver cancer, increased blood
clotting, retinopathy and corneal opacities. From reports, it is clear that repeated treatment would
produce an acquired tamoxifen resistance followed by tumor progression. In the recent years, site
directed drug delivery in a controlled manner has become a very popular and useful tool in
pharmaceutical area offering a wide range of actual and perceived advantages to some of these
chronic diseases. In order to overcome certain undesirable side effects, biodegradable polymers of
colloidal range have been developed to deliver drug in negligibly smaller doses to the targeted site of
interest. Polymeric nanoparticles have been found as the good vehicles for the delivery of
hydrophobic and hydrophilic drugs, since the drugs are protected from possible degradation by
enzymes. Since no attempts have been made to explain the physicochemical characteristics of
tamoxc incorporated ChtNP, we report on the preparation, characterization and safety aspects of
biodegradable ChtNP prepared by an IG technique.