In Vitro and In Vivo Assessment of Designed Melphalan Loaded Stealth Solid Lipid Nanoparticles for Parenteral Delivery

• Published in: BioNanoScience 2020-03, Vol.10 (1), p.168-190
• Main Authors: Rudhrabatla, V. S. A. Pavan, Sudhakar, Beeravelli, Reddy, K. V. N. Suresh
• Format: Article
• Language: English
• Subjects: Biocompatibility; Biological and Medical Physics; Biomaterials; Biophysics; Cell viability; Circuits and Systems; Design; Dialysis; Drug delivery systems; Efficiency; Encapsulation; Engineering; Homogenization; In vivo methods and tests; Lipids; Melphalan; Nanoparticles; Nanotechnology; Parameters; Particle size; pH effects; Pharmacokinetics; Pharmacology; Polydispersity; Stability; Stearin; Sterilization; Tristearin; Zeta potential
• ISSN: 2191-1630; 2191-1649
• DOI: 10.1007/s12668-019-00680-6

The aim of the present study is to develop the melphalan (MLN) loaded stealth solid lipid nanoparticles (SSLNs) for parenteral delivery by hot homogenization technique using central composite design. Amount of tristearin, soyalecithin, and DSPE-m-PEG-2000 is taken as independent factor whereas the particle size, % of encapsulation efficiency, and zeta potential are considered as dependent factors. Developed SSLNs were characterized through various physicochemical parameters, i.e., percentage of drug content, particle size, zeta potential, polydispersity, and percent encapsulation efficiency. The SSLNs were optimized using desirability and overlay plots, and optimized SSLNs were further characterized for various physicochemical parameters, i.e., in vitro drug release at pH 7.4, 6.5 and 5.5 by dialysis process, drug and excipient compatibility analysis (FTIR, DSC, TGA, SEM, and XRD), sterilization, in vitro cell viability and hematological studies, in vivo pharmacokinetics on rats, and stability, respectively. The % assay was found in the range 97.89 ± 0.9 to 101 ± 1.6%; particle size was found in the range of 106 ± 0.9 to 301 ± 1.2 nm whereas the zeta potential was found in the range of − 4 to -38 mV, respectively. The drug release of SSLN was found at around 100% at 28, 32, and 34 h for pH 7.4, 6.5 and 5.5 mediums, respectively. The lyophilized form of SSLNs showed better stability compared with SSLN suspension. The in vitro cell viability studies indicated that SSLNs showed superior results compared with their pure MLN solution. The in vivo pharmacokinetic studies revealed that SSLNs showed long circulation ( t 1/2 ), better residence time (MRT), and low elimination rate ( K el ) compared with pure MLN solution. Melphalan loaded stealth solid lipid nanoparticles were successfully designed using central composite design by high-pressure homogenization with low particle size and high encapsulation efficiency (92%) and are able to release the drug in controlled manner.