In Situ Gel Loaded with Chitosan-Coated Simvastatin Nanoparticles: Promising Delivery for Effective Anti-Proliferative Activity against Tongue Carcinoma.

Mallesh Kurakula,N Raghavendra Naveen

doi:10.3390/md18040201

Abstract

The goal of this study is to develop optimized chitosan-coated Simvastatin (SIM) nanoparticles (NPs) loaded in an in situ gel (ISG) formulation via a face-centered central composite design (FCCCD). Coated SIM-NPs were doped with Quercetin (QRC) using a modified nanoprecipitation method. The concentrations of poloxamer 188 (A) and chitosan (B) at five different levels, plus/minus alpha (+1.414 and −1.414: axial points), plus/minus 1 (factorial points) and the center point were optimized for particle size (PS-Y1), entrapment efficacy (EE-Y2) and stability index (SI-Y3). Based on the desirability approach, a formulation containing poloxamer 188 0.24% and chitosan 0.43% renders the prerequisites of optimum formulation for preparing SIM–QRC NP-loaded ISG. Scanning microscopy showed spherical SIM-NPs, indicating monodispersity in the range of 0.50 ± 0.04 nm with a charge of +32.42 mV. The optimized formulation indicated the highest EE 79.67% and better stability at 4 °C. Drug release from SIM–QRC NP-loaded ISG was slower to plateau by up to 96 h and, at the end of 168 h, only 65.12% of SIM was released in a more controlled manner in comparison to SIM–QRC NPs and plain SIM. ISG formulation showed a considerable increase in apoptosis occurrence through caspase-3 mediation and it also enhanced the tumor suppressor protein levels. Enhanced biological activity of SIM was observed due to QRC enabling promising drug and polymer synergistic interaction. The proposed formulation can provide a breakthrough in localized therapy, overcoming the potential drawbacks of systemic chemotherapy for tongue carcinoma.

Highlights

Oral cancers are the eighth most common cancers in the world, primarily located in the mouth, tongue or oropharynx [1]
When their concentrations are very low, formed nanoparticles show larger particle sizes and even higher concentrations of these factors, resulting in the formation of larger nanoparticles. This might be because of the repulsion of amino groups in chitosan molecules at higher concentrations and the addition of poloxamer 188 might promote further aggregation, which leads to precipitation, forming NPs with larger particle sizes [31]
The size of NPs can affect their distribution, for which lower liver uptake can be observed with smaller particle sizes of 25–50 nm in comparison to

Summary

Introduction

Oral cancers are the eighth most common cancers in the world, primarily located in the mouth, tongue or oropharynx [1]. The tongue is the most common site and oral squamous cell carcinoma (OSCC) represents 90%–95% of total intraoral carcinoma malignancies [2]. These arise initially from the lining of the tongue and appear like lumps with red or white spots. The exact etiology of tongue cancer is unknown, several risk factors like chewing tobacco, pan, and betel nuts have been identified, but these factors vary in different areas of the world [3,4,5].

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