Development of tamoxifen‐loaded surface‐modified nanostructured lipid carrier using experimental design: in vitro and ex vivo characterisation

The present study aimed to develop a surface‐modified biocompatible nanostructured lipid carrier (NLCs) system using polyoxyethylene (40) stearate (POE‐40‐S) to improve the oral bioavailability of poorly water‐soluble Biopharmaceutics Classification System class‐II drug like tamoxifen (TMX). Also aimed to screen the most influential factors affecting the particle size (PS) using Taguchi (L₁₂ (2¹¹)) orthogonal array design (TgL₁₂ OA). Then, to optimize the TMX loaded POE‐40‐S (P) surface‐modified NLCs (TMX‐loaded‐PEG‐40‐S coated NLC (PNLCs) or PNLCs) by central composite design (CCD) using a four‐factor, five‐level model. The most influential factors affecting the PS was screened and optimized. The in‐vitro study showed that increased drug‐loading (DL) and encapsulation efficiency (EE), decreased PS and charge, sustained drug release for the prolonged period of the time with good stability and suppressed protein adsorption. The Ex‐vivo study showed that decreased mucous binding with five‐fold enhanced permeability of PNLC formulation after surface modification with POE‐40‐S. The in‐vitro cytotoxicity study showed that the blank carrier is biocompatible and cytotoxicity of the formulation was dependent on the concentration of the drug. Finally, it can be concluded that the surface‐modified PNLCs formulation was an effective, biocompatible, stable formulation in the enhancement of dissolution rate, solubility, stability with reduced mucus adhesion and increased permeability thereby which indicates its enhanced oral bioavailability.Inspec keywords: nanoparticles, cellular biophysics, solubility, drug delivery systems, toxicology, adsorption, adhesion, dissolving, biomedical materials, encapsulation, polymers, proteins, nanomedicine, permeability, particle size, electrokinetic effectsOther keywords: water‐soluble BCS class‐II, TgL₁₂ OA, TMX‐loaded POE‐40‐S surface‐modified NLC, surface‐modified PNLC formulation, lipid‐based NLC system, oral bioavailability, stable formulation, biocompatible formulation, blank carrier, in vitro cytotoxicity, surface modification, PNLC formulation, drug release, central composite design, orthogonal array design, encapsulation efficiency, steric stabilisation effect, particle size, dissolution rate, polyoxyethylene stearate, surface‐modified biocompatible carrier system, systemic toxicity, water‐soluble drug, tamoxifen‐loaded surface‐modified nanostructured lipid carrier