QbD Supported Optimization of the Alginate-Chitosan Nanoparticles of Simvastatin in Enhancing the Anti-Proliferative Activity against Tongue Carcinoma.

Eman Alfayez,Haitham A Bukhary,Mallesh Kurakula,Waleed Y Rizg,N Raghavendra Naveen,Awaji Y Safhi,Amal M Sindi,Khaled M Hosny,Sarah Ali,Samar S Murshid

doi:10.3390/gels8020103

Abstract

The goal of the current study is to develop a chitosan alginate nanoparticle system encapsulating the model drug, simvastatin (SIM-CA-NP) using a novel polyelectrolytic complexation method. The formulation was optimized using the central composite design by considering the concentrations of chitosan and alginate at five different levels (coded as +1.414, +1, 0, −1, and −1.414) in achieving minimum particle size (PS-Y1) and maximum entrapment efficiency (EE-Y2). A total of 13 runs were formulated (as projected by the Design-Expert software) and evaluated accordingly for the selected responses. On basis of the desirability approach (D = 0.880), a formulation containing 0.258 g of chitosan and 0.353 g of alginate could fulfill the prerequisites of optimum formulation in achieving 142.56 nm of PS and 75.18% EE. Optimized formulation (O-SIM-CAN) was further evaluated for PS and EE to compare with the theoretical results, and relative error was found to be within the acceptable limits, thus confirming the accuracy of the selected design. SIM release from O-SIM-CAN was retarded significantly even beyond 96 h, due to the encapsulation in chitosan alginate carriers. The cell viability study and Caspase-3 enzyme assay showed a notable difference in contrast to that of plain SIM and control group. All these stated results confirm that the alginate-chitosan nanoparticulate system enhanced the anti-proliferative activity of SIM.

Highlights

Nanoparticles have gained huge attention as drug carriers
On basis of the above statements, the present study aims at developing alginate-chitosan nanocarriers for SIM encapsulation
Pure SIM and final optimized formulation were studied for compatibility using FTIR and the results were demonstrated in Table 1 and Figure 1

Summary

Introduction

Nanoparticles have gained huge attention as drug carriers. In particular, the polymerbased on nanoparticles [1,2], lipid-based [3,4], magnetic nanoparticles [5,6], and liposomes [7] are broadly studied under nanoformulations. There are natural and synthetic polymers that are flexible and are employed for many uses, inclusive of the pharma industry [9]. The natural hydrogel polymers such as alginate, gelatin, and collagen have the potential to hold abundant water, keeping the structure intact, and are employed to carry hydrophilic drugs. The majority of the alginate produced annually is utilized for pharma and biomedical purpose, and the rest in the food industry [10,11]. Following the post-development of alginate in the 1980s, their application was expanded as microparticles for encapsulation and several studies were conducted to formulate alginate nanoparticles [12,13]. The nanomaterials of alginate denote a rapid growth field, especially in the food and pharma industry, and in the academe [14]

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