Increase of acidification of synthetic brines by ultrasound-treated Lactiplantibacillus plantarum strains isolated from olives

This paper focused on the evaluation of Ultrasound effect on the growth patterns (3–6% of salt and 45 °C), acidification (pH-decrease), interactions with microorganisms, and membrane permeability of nine strains of Lactiplantibacillus plantarum. Ultrasound treatment was applied at 20% of net power by modulating duration (2–10 min) and pulses (2–10 s).Viable count (7.15–8.16 log CFU/mL) was never affected by Ultrasound, while the treatment increased the extent of pH decrease of at least three strains (109, 162 and c19). L. plantarum c19 was the best performer, as a low intensity treatment was able to increase its acidification, without affecting its growth. The effects could be attributed to an increased permeability of the cellular membrane, as suggested by the increase of released intracellular components. Other factors should be further assessed (e.g. possible changes in the metabolism) and the performances of Ultrasound-treated strains in real brines.     

In vitro measurement of attenuation and nonlinear scattering from echogenic liposomes

Echogenic liposomes (ELIP) are an excellent candidate for concurrent imaging and drug delivery applications. They combine the advantages of liposomes-biocompatibility and ability to encapsulate both hydrophobic and hydrophilic drugs-with strong reflections of ultrasound. The objective of this study is to perform a detailed in vitro acoustic characterization - including nonlinear scattering that has not been studied before - along with an investigation of the primary mechanism of echogenicity. Both components are critical for developing viable clinical applications of ELIP. Mannitol, a cryoprotectant, added during the preparation of ELIP is commonly believed to be critical in making them echogenic. Accordingly, here ELIP prepared with varying amount of mannitol concentration are investigated for their pressure dependent linear and non-linear scattered responses. The average diameter of these liposomes is measured to be 125-185 nm. But they have a broad size distribution including liposomes with diameters over a micro-meter as observed by TEM and AFM. These larger liposomes are critical for the overall echogenicity. Attenuation through liposomal solution is measured with four different transducers (central frequencies 2.25, 3.5, 5, 10 MHz). Measured attenuation increases linearly with liposome concentration indicating absence of acoustic interactions between liposomes. Due to the broad size distribution, the attenuation shows a flat response without a distinct peak in the range of frequencies (1-12 MHz) investigated. A 15-20 dB enhancement with 1.67 μg/ml of lipids is observed both for the scattered fundamental and the second harmonic responses at 3.5 MHz excitation frequency and 50-800 kPa amplitude. It demonstrates the efficacy of ELIP for fundamental as well as harmonic ultrasound imaging. The scattered response however does not show any distinct subharmonic peak for the acoustic excitation parameters studied. Small amount of mannitol proves critical for echogenicity. However, mannitol concentration above 100 mM shows no effect.     

One injection for one-week controlled release: In vitro and in vivo assessment of ultrasound-triggered drug release from injectable thermoresponsive biocompatible hydrogels

Episodic release of bioactive compounds is often necessary for appropriate biological effects under specific physiological conditions. Here, we aimed to develop an injectable, biocompatible, and thermosensitive hydrogel system for ultrasound (US)-triggered drug release. An mPEG-PLGA-BOX block copolymer hydrogel was synthesized. The viscosity of 15 wt% hydrogel is 0.03 Pa*s at 25 °C (liquid form) and 34.37 Pa*s at 37 °C (gel form). Baseline and US-responsive in vitro release profile of a small molecule (doxorubicin) and that of a large molecule (FITC-dextran), from the hydrogel, was tested. A constant baseline release was observed in vitro for 7 d. When triggered by US (1 MHz, continuous, 0.4 W/cm²), the release rate increased by approximately 70 times. Without US, the release rate returned to baseline. Baseline and US-responsive in vivo release profile of doxorubicin was tested by subcutaneous injection in the back of mice and rats. Following injection into the subcutaneous layer, in vivo results also suggested that the hydrogels remained in situ and provided a steady release for at least 7 d; in the presence of the US-trigger, in vivo release from the hydrogel increased by approximately 10 times. Therefore, the mPEG-PLGA-BOX block copolymer hydrogel may serve as an injectable, biocompatible, and thermosensitive hydrogel system that is applicable for US-triggered drug release.