Research Article
Subacute Toxicity Profile of Lacidipine Nanoformulation in
Wistar Rats
Rupesh Shirodkar,
1
Chandrasekhar Misra,
2
Chethan GH,
2
Pallavi Shetty,
1
Zenab Attari,
1
Srinivas Mutalik,
1
and Shaila Lewis
1
1
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal,
Karnataka 576104, India
2
Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal,
Karnataka 576104, India
Correspondence should be addressed to Shaila Lewis; s.lewis@manipal.edu
Received 6 March 2015; Accepted 25 April 2015
Academic Editor: Tao Sun
Copyright © 2015 Rupesh Shirodkar et al. Tis 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.
Te present study was aimed at investigating the safety of Lacidipine (LCDP) loaded nanostructured lipid carriers (NLCs) in
Wistar rats. NLCs were formulated using ultrasound dispersion technique. Animals were orally treated once daily with NLCs
containing 0.140 mg, 0.350 mg, and 0.875 mg of LCDP as low, medium, and high dose per kg body weight, respectively, during
28 days along with blank formulation and pure LCDP. Control rats were fed with water. Animals were observed throughout
experiment period and their body weight was recorded once weekly. Overnight fasted rats were sacrifced on the 29th day. Study
revealed no signs or symptoms of toxicity or morbidity. No signifcant changes in the body weight were observed between treated
and control group. Signifcant increase in lef testis weight and liver weight was observed in male and female rats, respectively.
Haematological estimation revealed signifcant decrease in haemoglobin count in male rats while female rats showed signifcant
increase in granulocyte count. All the serum clinical parameters were within the normal range and no gross histopathological
changes were observed. No delayed efect was noted in satellite group. Te results indicate that developed LCDP loaded NLCs are
safe when administered orally in rats.
1. Introduction
Recent trend is focused on nanotechnology based drug
delivery system with the aim either to improve solubility
or to enhance bioavailability in order to achieve satisfactory
therapeutic efcacy [1]. However, the research involving the
toxicological impact and hazards of nanoparticles is still in its
initial stage [2]. Among various nanoparticulate drug deliv-
ery systems, nanostructured lipid carriers (NLCs) were devel-
oped to overcome the disadvantages of solid lipid nanopar-
ticles, namely, lower loading capacity and drug expulsion
during storage [3]. Lacidipine (LCDP) was classifed as per
Biopharmaceutics Classifcation System (BCS) as class II
drug [4]. LCDP is a dihydropyridine calcium channel blocker
used in the treatment of hypertension with more pronounced
vascular selectivity [5]. Upon oral administration, LCDP is
poorly absorbed from gastrointestinal tract and undergoes
extensive frst pass metabolism in the liver by CYP3A4
enzymes, resulting in 2 to 9% bioavailability [6, 7]. Literature
survey revealed development of NLCs for improving the
bioavailability of lipophilic and low bioavailable drugs [1, 8].
To enhance the bioavailability of LCDP, it was formulated
into NLCs. Earlier studies however indicated slight increase
in alkaline phosphatase (ALP) level which gets normalized
on long term administration [9]. LCDP was also tested in
normotensive rats and results obtained from chemistry anal-
ysis revealed slight variations in the levels of creatinine kinase
(CK), serum glutamate oxaloacetic transaminase (SGOT),
and alanine transaminase (ALT) levels. Te variations were
however found to be within normal biologic limits [10]. For-
mulating LCDP into NLCs may improve its pharmacological
activity. To evaluate whether such incorporation has any toxic
Hindawi Publishing Corporation
e Scientific World Journal
Volume 2015, Article ID 947623, 12 pages
http://dx.doi.org/10.1155/2015/947623