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Acoustic Cavitation-Assisted Formulation of Solid Lipid Nanoparticles using Different Stabilizers.

ABSTRACT: Because of excellent bioavailability and high biocompatibility, solid lipid nanoparticles (SLNs) have gained attention in recent years, especially in drug delivery systems. SLNs are composed of a drug that is loaded in a lipid matrix and stabilized by surfactants. In this work, we have investigated the feasibility of the acoustic cavitation-assisted hot melt mixing method for the formulation of SLNs using different stabilizers. A lipid Compritol 888 ATO (CPT) and a poorly water-soluble drug ketoprofen (KP) were used as a model lipid and drug, respectively. Gelucire 50/13 (GEL), poloxamer 407 (POL), and Pluronic F-127 (PLU) were used as the stabilizers. The effect of the stabilizers on the physico-chemical properties of SLNs was thoroughly studied in this work. The particle size and stability in water at different temperatures were measured using a dynamic light scattering method. The spherical shape (below 250 nm) and core-shell morphology were confirmed by field-emission scanning electron microscopy and transmission electron microscopy. The chemical, crystal, and thermal properties of SLNs were studied by FTIR, XRD analysis, and DSC, respectively. SLNs prepared using different stabilizers showed an encapsulation efficiency of nearly 90% and a drug loading efficiency of 12%. SLNs showed more than 90% of drug released in 72 h and increased with pH was confirmed using in vitro drug release studies. SLNs were nontoxic to raw 264.7 cells. All stabilizers were found suitable for acoustic cavitation-assisted SLN formulation with high encapsulation efficiency and drug loading and good biocompatibility.

SUBMITTER: Kumar R

PROVIDER: S-EPMC6705237 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Acoustic Cavitation-Assisted Formulation of Solid Lipid Nanoparticles using Different Stabilizers.

Kumar Raj R Singh Ashutosh A Garg Neha N

ACS omega 20190807 8

Because of excellent bioavailability and high biocompatibility, solid lipid nanoparticles (SLNs) have gained attention in recent years, especially in drug delivery systems. SLNs are composed of a drug that is loaded in a lipid matrix and stabilized by surfactants. In this work, we have investigated the feasibility of the acoustic cavitation-assisted hot melt mixing method for the formulation of SLNs using different stabilizers. A lipid Compritol 888 ATO (CPT) and a poorly water-soluble drug keto ...[more]

PMID: 31460464

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Project description:The aim of the study was the production of solid lipid nanoparticles (SLN) loaded with ciprofloxacin (CIP) through two different production techniques, quasi-emulsion solvent diffusion (QESD) and solvent injection (SI). In order to efficaciously entrap the commercial salt form (hydrochloride) of the antibiotic in these lipid systems, a conversion of CIP hydrochloride to the free base was realized in situ, through the addition of triethylamine. To ensure physical stability to the carriers over time and ameliorate the interaction with bacterial cell membranes, positively charged SLN were produced by addition of the cationic lipid didecyldimethylammonium bromide (DDAB). Homogeneous SLN populations with a mean particle sizes of 250?350 nm were produced by both methods; drug encapsulation was over 85% for most samples. The SLN were physically stable for up to nine months both at 4 °C and 25 °C, although the former condition appears more suitable to guarantee the maintenance of the initial particle size distribution. As expected, CIP encapsulation efficiency underwent a slight reduction after nine months of storage, although the initial high drug content values would ensure a residual concentration of the antibiotic in the SLN still appropriate to exert an acceptable antibacterial activity. Selected SLN formulations were subjected to an in vitro microbiological assay against different bacterial strains, to verify the effect of nanoencapsulation on the cell growth inhibitory activity of CIP. In general, CIP-SLN produced without DDAB showed MIC values for CIP comparable to those of the free drug. Conversely, addition of increasing percentages of the cationic lipid, reflected by a progressive increase of the positive value of the Zeta potential, showed a variety of MIC values against the various bacterial strains, but with values 2?4 order of dilution lower than free CIP. An hypothesis of the effect of the cationic lipid upon the increased antibacterial activity of CIP in the nanocarriers is also formulated.

Project description:Ultrasound is widely applied in medical diagnosis and therapy due to its safety, high penetration depth, and low cost. In order to improve the contrast of sonographs and efficiency of the ultrasound therapy, echogenic gas bodies or droplets (with diameters from 200 nm to 10 µm) are often used, which are not very stable in the bloodstream and unable to penetrate into target tissues. Recently, it was demonstrated that nanobubbles stabilized by nanoparticles can nucleate ultrasound responsive microbubbles under reduced acoustic pressures, which is very promising for the development of nanoscale (<100 nm) ultrasound agents. However, there is still very little understanding about the effects of nanoparticle properties on the stabilization of nanobubbles and nucleation of acoustic cavitation by these nanobubbles. Here, a series of mesoporous silica nanoparticles with sizes around 100 nm but with different morphologies were synthesized to understand the effects of nanoparticle porosity, surface roughness, hydrophobicity, and hydrophilic surface modification on acoustic cavitation inception by porous nanoparticles. The chemical analyses of the nanoparticles showed that, while the nanoparticles were prepared using the same silica precursor (TEOS) and surfactant (CTAB), they revealed varying amounts of carbon impurities, hydroxyl content, and degrees of silica crosslinking. Carbon impurities or hydrophobic modification with methyl groups is found to be essential for nanobubble stabilization by mesoporous silica nanoparticles. The acoustic cavitation experiments in the presence of ethanol and/or bovine serum albumin (BSA) demonstrated that acoustic cavitation is predominantly nucleated by the nanobubbles stabilized at the nanoparticle surface not inside the mesopores. Finally, acoustic cavitation experiments with rough and smooth nanoparticles were suggested that a rough nanoparticle surface is needed to largely preserve surface nanobubbles after coating the surface with hydrophilic macromolecules, which is required for in vivo applications of nanoparticles.

Dataset Information

Acoustic Cavitation-Assisted Formulation of Solid Lipid Nanoparticles using Different Stabilizers.

Publications

Acoustic Cavitation-Assisted Formulation of Solid Lipid Nanoparticles using Different Stabilizers.

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