Hypoblast from human pluripotent stem cells regulates epiblast development.

Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study of human embryos1-8. Despite the importance of human embryology, ethical and legal restrictions have limited post-implantation-stage studies. Thus, recent efforts have focused on developing in vitro self-organizing models using human stem cells9-17. Here, we report genetic and non-genetic approaches to generate authentic hypoblast cells (naive hPSC-derived hypoblast-like cells (nHyCs))-known to give rise to one of the two extraembryonic tissues essential for embryonic development-from naive human pluripotent stem cells (hPSCs). Our nHyCs spontaneously assemble with naive hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity. In the presence of additional naive hPSC-derived analogues of the second extraembryonic tissue, the trophectoderm, the efficiency of bilaminoid formation increases from 20% to 40%, and the epiblast within the bilaminoids continues to develop in response to trophectoderm-secreted IL-6. Furthermore, we show that bilaminoids robustly recapitulate the patterning of the anterior-posterior axis and the formation of cells reflecting the pregastrula stage, the emergence of which can be shaped by genetically manipulating the DKK1/OTX2 hypoblast-like domain. We have therefore successfully modelled and identified the mechanisms by which the two extraembryonic tissues efficiently guide the stage-specific growth and progression of the epiblast as it establishes the post-implantation landmarks of human embryogenesis.

Functional calcium-responsive parathyroid glands generated using single-step blastocyst complementation.

Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid gland cells generated from pluripotent stem cells in vitro to date cannot mimic the physiological responses to extracellular calcium that are essential for calcium homeostasis. We thus hypothesized that blastocyst complementation (BC) could be a better strategy for generating functional PTG cells and compensating loss of parathyroid function. We here describe generation of fully functional PTGs from mouse embryonic stem cells (mESCs) with single-step BC. Using CRISPR-Cas9 knockout of Glial cells missing2 (Gcm2), we efficiently produced aparathyroid embryos for BC. In these embryos, mESCs differentiated into endocrinologically mature PTGs that rescued Gcm2-/- mice from neonatal death. The mESC-derived PTGs responded to extracellular calcium, restoring calcium homeostasis on transplantation into mice surgically rendered hypoparathyroid. We also successfully generated functional interspecies PTGs in Gcm2-/- rat neonates, an accomplishment with potential for future human PTG therapy using xenogeneic animal BC. Our results demonstrate that BC can produce functional endocrine organs and constitute a concept in treatment of hypoparathyroidism.

Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells.

The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative medicine. Mouse wild-type PSCs injected into Pdx1(-/-) (pancreatogenesis-disabled) mouse blastocysts developmentally compensated vacancy of the pancreatic "developmental niche," generating almost entirely PSC-derived pancreas. To examine the potential for xenogenic approaches in blastocyst complementation, we injected mouse or rat PSCs into rat or mouse blastocysts, respectively, generating interspecific chimeras and thus confirming that PSCs can contribute to xenogenic development between mouse and rat. The development of these mouse/rat chimeras was primarily influenced by host blastocyst and/or foster mother, evident by body size and species-specific organogenesis. We further injected rat wild-type PSCs into Pdx1(-/-) mouse blastocysts, generating normally functioning rat pancreas in Pdx1(-/-) mice. These data constitute proof of principle for interspecific blastocyst complementation and for generation in vivo of organs derived from donor PSCs using a xenogenic environment.

Usefulness of Ag Additional Filter on Image Quality and Radiation Dose for Low-Dose Chest Computed Tomography.

OBJECTIVE: This study aimed to evaluate the effect of a silver (Ag) additional filter on dose characteristics and image quality in low-dose chest computed tomography (CT). METHODS: A dose evaluation phantom, physical evaluation phantom, and chest phantom were scanned with and without an Ag additional filter. The doses were adjusted so that the displayed the volume CT dose indexes (CTDI vol ) were from 0.3 to 1.6 mGy. For dose characteristics, the spectrum of photon energies and the measured CTDI vol were calculated for each scanning condition. For task-based image quality analysis, task transfer function, noise power spectrum, and system performance were evaluated. Streak artifacts, image noise, and contrast-to-noise ratio were quantified using a chest phantom. RESULTS: With the Ag additional filter, mean energy was 22% higher and the CTDI vol was approximately 30% lower than those without the Ag additional filter. The task transfer function and noise power spectrum with the Ag additional filter were lower than those without the Ag additional filter. The system performance with the Ag additional filter was similar to that without the Ag additional filter. The Ag additional filter reduced streak artifact near the lung apex and image noise in the lung fields. The contrast-to-noise ratio was slightly higher with the Ag additional filter than that without the Ag additional filter. CONCLUSIONS: The output dose and spatial resolution with the Ag additional filter were lower than those without the Ag additional filter. However, this filter helped reduce the radiation dose, image noise, and streak artifacts, particularly when scanning at ultralow doses.

Pharmacokinetic control of orally dosed cyclosporine A with mucosal drug delivery system.

This study aimed to control the oral absorption of cyclosporine A (CsA) with the use of a mucosal drug delivery system (mDDS). Mucopenetrating nanocarriers (MP/NCs) and mucoadhesive nanocarriers (MA/NCs) were prepared by flash nanoprecipitation employing polystyrene-block-poly(ethylene glycol) and polystyrene-block-poly(N,N-dimethyl aminoethyl methacrylate), respectively. Their particle distribution in the rat gastrointestinal tract were visualized by fluorescent imaging. Plasma concentrations were monitored after oral administration of CsA-loaded MP/NCs (MP/CsA) and MA/NCs (MA/CsA) to rats. MP/NCs and MA/NCs had a particle size below 200 nm and ζ-potentials of 4 and 40 mV, respectively. The results from in vitro experiments demonstrated mucopenetration of MP/NCs and mucoadhesion of MA/NCs. Confocal laser scanning microscopic images showed diffusion of MP/NCs in the gastrointestinal mucus towards epithelial cells and localization of MA/NCs on the surface of the gastrointestinal mucus layer. In a pH 6.8 solution, rapid and sustained release of CsA were observed for MP/CsA and MA/CsA, respectively. After oral dosing (10 mg-CsA/kg) to rats, amorphous CsA powder exhibited a time to maximum plasma concentration (Tmax) of 3.4 h, maximum plasma concentration (Cmax) of 0.12 µg/mL, and bioavailability of 0.7%. Compared with amorphous CsA powder, MP/CsA shortened Tmax by 1.1 to 2.3 h and increased the bioavailability by 43-fold to 30.1%, while MA/CsA prolonged Tmax by 3.4 to 6.8 h with Cmax and bioavailability of 0.65 µg/mL and 11.7%, respectively. These pharmacokinetic behaviors would be explained by their diffusion and release properties modulated by polymeric surface modification. The mDDS approach is a promising strategy for the pharmacokinetic control of orally administered CsA.

Nanocarriers with long-term retention in the respiratory system for prolonged drug exposure.

This study was the first attempt to visualize pulmonary retention of nanocarriers (NCs) with the use of the P2 probe, a new water-initiated aggregation-caused fluorescent-quenching (ACQ) dye, for the development of NCs with long-lasting retention in the respiratory system (RS). Flash nanoprecipitation was used to fabricate mucopenetrating NCs (MP/NCs) and mucoadhesive NCs (MA/NCs). Both NCs were labeled with the P2 probe, and their distribution and retention in RS were visualized after intratracheal administration to rats. MP/NCs and MA/NCs had a mean diameter below 200 nm and ζ-potential of 0 and 48 mV, respectively. MA/NCs showed three times stronger interactions with mucin than MP/NCs, resulting in significantly lower diffusiveness in mucus. The P2 probe exhibited an ACQ effect with negligible rekindling in simulated lung fluid, and the spectroscopic data suggested applicability to reliable imaging of insufflated NCs. In confocal laser scanning microscopic and in vivo imaging system images of the rat RS, MA/NCs were locally deposited in the respiratory tract and transported toward the pharynx by mucocilliary clearance (MCC). In contrast, MP/NCs diffused in the respiratory mucus were less subject to the influence of MCC. Based on the results from the bioimaging study using the P2 probe, MP/NCs could offer enhanced pulmonary retention of drugs compared with MA/NCs.

Benchmarking Refined and Unrefined AlphaFold2 Structures for Hit Discovery.

The recently developed AlphaFold2 (AF2) algorithm predicts proteins' 3D structures from amino acid sequences. The open AlphaFold protein structure database covers the complete human proteome. Using an industry-leading molecular docking method (Glide), we investigated the virtual screening performance of 37 common drug targets, each with an AF2 structure and known holo and apo structures from the DUD-E data set. In a subset of 27 targets where the AF2 structures are suitable for refinement, the AF2 structures show comparable early enrichment of known active compounds (avg. EF 1%: 13.0) to apo structures (avg. EF 1%: 11.4) while falling behind early enrichment of the holo structures (avg. EF 1%: 24.2). With an induced-fit protocol (IFD-MD), we can refine the AF2 structures using an aligned known binding ligand as the template to improve the performance in structure-based virtual screening (avg. EF 1%: 18.9). Glide-generated docking poses of known binding ligands can also be used as templates for IFD-MD, achieving similar improvements (avg. EF 1% 18.0). Thus, with proper preparation and refinement, AF2 structures show considerable promise for in silico hit identification.

Interspecies organogenesis generates autologous functional islets.

Islet transplantation is an established therapy for diabetes. We have previously shown that rat pancreata can be created from rat pluripotent stem cells (PSCs) in mice through interspecies blastocyst complementation. Although they were functional and composed of rat-derived cells, the resulting pancreata were of mouse size, rendering them insufficient for isolating the numbers of islets required to treat diabetes in a rat model. Here, by performing the reverse experiment, injecting mouse PSCs into Pdx-1-deficient rat blastocysts, we generated rat-sized pancreata composed of mouse-PSC-derived cells. Islets subsequently prepared from these mouse-rat chimaeric pancreata were transplanted into mice with streptozotocin-induced diabetes. The transplanted islets successfully normalized and maintained host blood glucose levels for over 370 days in the absence of immunosuppression (excluding the first 5 days after transplant). These data provide proof-of-principle evidence for the therapeutic potential of PSC-derived islets generated by blastocyst complementation in a xenogeneic host.

Dual-energy CT imaging of atherosclerotic plaque using novel ultrasmall superparamagnetic iron oxide in hyperlipidemic rabbits.

BACKGROUND: A study using magnetic resonance imaging (MRI) revealed that ultra-small superparamagnetic iron oxide is phagocytosed by macrophages. However, MRI has limitations in obtaining clear images due to its poor spatial and temporal resolutions. PURPOSE: To examine whether the use of dual-energy computed tomography (DECT) facilitated the visualization of carboxymethyl-diethylaminoethyl dextran magnetite ultra-small superparamagnetic iron oxide (CMEADM-U) accumulation in arteriosclerotic lesions using hyperlipidemic rabbits. MATERIAL AND METHODS: CMEADM-U at 0.5 mmol Fe/kg was administered to Watanabe hereditary atherosclerotic (WHHL) rabbits (n = 6, 24 sections) and New Zealand white (NZW) rabbits (n = 2, 6 sections). After 72 h, DECT was performed to prepare virtual monochromatic images (35 keV, 70 keV) and an iron-based map. Subsequently, the aorta was collected along with hematoxylin and eosin staining, Berlin blue (BB) staining, and RAM11 immunostaining. RESULTS: In the WHHL rabbits, CMEADM-U accumulation was not observed at 70 keV. However, CMEADM-U accumulation consistent with an arteriosclerotic lesion was observed at 35 keV and the iron-based map. On the other hand, in the NZW rabbits, there was no accumulation of CMEADM-U in any images. Further, there were significant differences in the iron-based map value at the site of accumulation among the grades of expression on BB staining and RAM11 immunostaining. In addition, there was a good correlation at 35 kev and iron-based map value (r = 0.42; P < 0.05). CONCLUSION: DECT imaging for CMEADM-U facilitated the assessment of macrophage accumulation in atherosclerotic lesions in an in vivo study using a rabbit model of induced aortic atherosclerosis.

Self-micellizing solid dispersion of tacrolimus: Physicochemical and pharmacokinetic characterization.

The present study was undertaken to develop a self-micellizing solid dispersion (SMSD) of tacrolimus (TAC) to improve the biopharmaceutical properties of TAC. An SMSD formulation of TAC (SMSD/TAC) and amorphous solid dispersion formulation of TAC (ASD/TAC) were prepared with Soluplus® , an amphiphilic copolymer, and hydroxypropyl cellulose, respectively. Physicochemical properties were characterized in terms of morphology, crystallinity, storage stability, interaction of TAC with Soluplus® , and micelle-forming potency; pharmacokinetic behavior was also evaluated in rats. Tacrolimus in both formulations was in an amorphous state. After storage at 40°C/75% relativity humidity for 4 weeks, there were no significant changes in the crystallinity of TAC between nonaged and aged SMSD/TAC, whereas slight recrystallization was observed in aged ASD/TAC. The results of circular dichroism (CD) and infrared spectroscopic analyses were indicative of the potent drug-polymer interaction in SMSD/TAC, possibly leading to the prevention of recrystallization. Compared with other TAC samples, SMSD/TAC exhibited significant improvement in the dissolution behavior of TAC through the immediate formation of fine micelles. After the oral administration of TAC samples (10 mg TAC/kg) to rats, there was marked enhancement in systemic exposure to TAC with both formulations; in particular, SMSD/TAC achieved an increase in bioavailability ca. 20-fold higher than crystalline TAC. The SMSD approach might provide an effective dosage form for TAC with enhanced physicochemical stability and oral absorption.

Celecoxib-Loaded Self-micellizing Solid Dispersion Suppresses Its Delayed Absorption in Rats with Impaired Gastrointestinal Motility.

The aim of this study was to develop a self-micellizing solid dispersion of celecoxib (SMSD/CEL) with enhanced dissolution to suppress a delay in absorption under impairment of gastrointestinal (GI) secretion and motility induced by severe pain. Soluplus®-based SMSD/CEL was prepared by lyophilization and physiochemically characterized. A pharmacokinetic study of orally-dosed CEL samples was carried out in rats with propantheline (PPT)-induced the impairment of GI secretion and motility. SMSD/CEL was micellized in aqueous media with a mean diameter of 153 nm, and it showed improved dissolution behavior of CEL under acidic conditions with 2.1-fold higher dissolved CEL at 120 min than crystalline CEL. SMSD/CEL was found to be in an amorphous state, and there was no significant crystallization even after storage under accelerated conditions for 8 weeks, indicating relatively high storage stability of the amorphous form. Orally-dosed crystalline CEL in PPT-treated rats showed a delayed mean absorption time (MAT) and area under the curve of plasma concentration versus time from 0 to 4 h (AUC0-4) was reduced to 12% compared with that in normal rats, whereas SMSD/CEL suppressed the delay and decrease of absorption in PPT-treated rats. From these findings, SMSD/CEL might be efficacious to suppress poor and delayed absorption of CEL for better pain medication in the presence of impaired GI secretion and motility associated with severe pain.

Polylysine-Containing Hydrogel Formulation of Fuzapladib, Inhibitor of Leukocyte-Function Associated Antigen-1 (LFA-1) Activation, for Sustained Release.

The aim of the present study was to develop an injectable hydrogel (HG) formulation of fuzapladib sodium (FZP), an animal drug for acute pancreatitis (AP), with the use of polyethyleneoxide (PEO) and polylysine (pLys), a cationic polymer. A mixture of pLys and FZP was added to PEO to prepare an HG formulation, and the formulation was optimized by release test and viscosity measurements. Circular dichroism (CD) and infrared absorption (IR) spectral analyses were applied to clarify the intermolecular interactions between FZP and pLys. The pharmacokinetic behavior of FZP was evaluated after a subcutaneous administration of FZP samples (2.0 mg-FZP/kg) to rats. Although the immediate release of FZP was observed for the HG formulation, the addition of pLys at a 20-fold amount of FZP or higher led to the sustained release of FZP. Considering release behavior, the concentration of pLys was optimized as 100-fold that of FZP in the HG formulation. CD and IR spectroscopic analyses of FZP and/or pLys demonstrated an intermolecular interaction between FZP and pLys, as evidenced by the slight spectral transition. After a subcutaneous administration of HG formulation containing pLys to rats, compared with FZP alone, significant differences were observed in the pharmacokinetic behavior with a decrease of Cmax from 2.3 to 0.9 mg/mL and slower elimination kinetics. HG formulation using pLys might be a viable dosage option for FZP for the treatment of AP in animals.

Lysophosphatidylcholine-based liposome to improve oral absorption and nephroprotective effects of astaxanthin.

BACKGROUND: The present study was aimed to develop astaxanthin (AX)-loaded liposomes by the utilization of soybean phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) to improve the nutraceutical properties of AX. AX-loaded liposomes consisting of PC (PC/AX) and LPC (LPC/AX) were evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. RESULTS: PC/AX and LPC/AX had uniform size distributions with a mean particle size of 254 and 148 nm, respectively. Under pH 6.8 conditions, both liposomes exhibited improved dissolution behavior of AX compared with crystalline AX (cAX). In particular, LPC/AX showed a sevenfold higher release of AX than PC/AX. After the oral administration of LPC/AX (33.2 mg AX kg-1 ) to rats, there was a significant increase in systemic exposure to AX, as evidenced by a 15-fold higher AUC0-24 h than PC/AX. However, the oral absorption of AX in the cAX group was negligible. Based on the results of histological analysis and measurement of plasma biomarkers, LPC/AX exhibited improved nephroprotective effects of AX in the rat model of kidney injury. CONCLUSION: From these observations, a strategic application of the LPC-based liposomal approach might be a promising option to improve the nutraceutical properties of AX. © 2022 Society of Chemical Industry.

Solid lipid nanoparticles of lutein with improved dissolution behavior and oral absorption.

The present study aimed to develop solid lipid nanoparticles of lutein (SLN/LT) with improved dissolution behavior and oral absorption. SLN/LT were prepared by a flash nanoprecipitation method using a multi-inlet vortex mixer, and their physicochemical, photochemical, and pharmacokinetic properties were evaluated. The mean particle size of SLN/LT re-dispersed in water was 237 nm, and small spherical particles with no significant aggregation were observed. LT significantly generated singlet oxygen upon exposure to pseudo-sunlight (250 W/m2, 1 h), suggesting its high photoreactivity. The remaining LT in LT solution, crystalline LT, and SLN/LT after irradiation with pseudo-sunlight (250 W/m2, 2 h) were 56.3, 86.7, and 101%, respectively. SLN/LT showed improved dissolution behavior of LT in simulated intestinal fluid, and the dissolved amounts of LT at 2 h were at least 50 times higher than that of crystalline LT. Orally administered SLN/LT (100 mg-LT/kg) exhibited enhanced oral absorption of LT, as evidenced by a relative bioavailability of 3.7 to crystalline LT in rats. SLN/LT may be a promising dosage form for orally available LT supplements, possibly leading to enhanced nutritional functions of LT.

Development of Poly(lipoic acid) Nanoparticles with Improved Oral Bioavailability and Hepatoprotective Effects of Quercetin.

Quercetin (QUE)-loaded poly(lipoic acid) nanoparticles (QUE/pLA) were developed to improve chemical stability in the gastrointestinal (GI) tract, oral bioavailability (BA), and pharmacological properties of QUE. QUE/pLA was prepared by emulsion solvent evaporation with ultrasonication followed by freeze-drying. Its mean particle size was 185 nm, with a high encapsulation efficiency of QUE (84.8%). QUE/pLA exhibited sustained release of QUE with improved dissolution compared with crystalline QUE and significantly enhanced chemical stability under physiological pH in the GI tract. Orally dosed QUE/pLA (50 mg QUE/kg) in rats exhibited significantly prolonged systemic exposure, possibly due to the sustained release of QUE. The oral BAs of QUE in QUE/pLA and crystalline QUE groups were 29 and 0.19%, respectively, suggesting significant enhancement of oral absorbability, likely due to the improved stability and dissolution property of QUE in the GI tracts. In hepatic injury model rats, QUE/pLA (50 mg QUE/kg) led to marked reductions in the plasma biomarker levels of alanine aminotransferase and aspartate aminotransferase by 70 and 46%, respectively, compared with the vehicle group. QUE/pLA also showed improved antioxidant potential as evidenced by the enhanced activities of hepatic glutathione, superoxide dismutase, and a decrease in the level of malondialdehyde, a marker of lipid peroxidation. Based on these findings, QUE/pLA might be a promising option to improve both the nutraceutical and pharmaceutical properties of QUE.

Comparison of erector spinae fatigability between female patients with Parkinson's disease and healthy individuals: a cross sectional pilot study.

BACKGROUND: Postural abnormality is one of the main symptoms of Parkinson's disease (PD). The erector spinae muscles play an important role in maintaining an upright posture, but the fatigability of the erector spinae in patients with PD is unknown. The purpose of this study was to compare the trunk extension maximum voluntary contraction (MVC) and the fatigability of the erector spinae between female patients with PD and healthy volunteers. METHODS: Th participants of this cross-sectional pilot study comprised 19 patients with PD and nine healthy volunteers matched for sex, age, and physical characteristics as a control group. The MVC of all participants was measured, and after sufficient rest, the Sørensen back endurance test was conducted to the point of exhaustion. The muscle activity of the erector spinae during the Sørensen back endurance test was measured using surface electromyography. The median frequency (MF) slope, which is an index of fatigability, was calculated from the recorded surface muscle activity by means of power spectrum analysis using a Fast Fourier transformation. RESULTS: Nine of the 19 patients with PD were unable to perform the Sørensen back endurance test, and a lower proportion of the PD group were able to perform it compared with the control group. The MVC of those patients with PD who were able to perform the Sørensen back endurance test was lower than that of the control group, and the time for which the pose could be maintained was shorter. There was no significant difference between the MF slope on the left and right side in the PD group, and it was higher on both sides than in the control group. CONCLUSION: This is the first study to demonstrate a reduction of maximum muscle strength and great fatigability of the erector spinae in patients with PD. This discovery strongly underlines the need for paraspinal muscle training from an early stage with the aim of preventing the progression of postural abnormality in patients with PD.

Nanocrystal solid dispersion of fuzapladib free acid with improved oral bioavailability.

This study aimed to develop an oral nanocrystal solid dispersion (nCSD) of fuzapladib (FZP) with enhanced absorbability for the treatment of acute pancreatitis (AP). The hydration properties of crystalline FZP free acid (crystalline FZP) and FZP sodium salt (FZP/Na) were assessed to select a stable crystal form. The nCSD of FZP free acid (nCSD/FZP) was prepared using a multi-inlet vortex mixer and evaluated in terms of physicochemical and pharmacokinetic properties. The results of X-ray powder diffraction analysis indicated that crystalline FZP was stable as an anhydrate, while FZP/Na was converted to its monohydrate at water activity of above 0.2. The nanocrystals in nCSD/FZP were dispersed in hydroxy propyl cellulose-SSL, and their mean particle size were 160 nm with uniform spherical shape. In dissolution testing, nCSD/FZP exhibited rapid dissolution compared with crystalline FZP and reached a saturated concentration of FZP within initial 30 min. After oral administration (2 mg-FZP/kg) to rats, the maximum plasma concentration and bioavailability were 7.3- and 5.2-fold higher for nCSD/FZP than crystalline FZP, respectively, due to improved dissolution by nanosization. In conclusion, nCSD/FZP may be a novel oral dosage form with enhanced absorbability facilitating potent therapeutic effects of FZP for the treatment of AP in animals.

Strategic application of liposomal system to R-α-lipoic acid for the improvement of nutraceutical properties.

R-α-lipoic acid (RLA) and dihydrolipoic acid (DHLA), a reduced form of RLA, are potent endogenous antioxidants that can reduce oxidative damage. Despite their numerous nutraceutical potentials, clinical applications of RLA are still limited due to its poor solubility and stability problems. This study aimed to develop an RLA-loaded liposome (LIP/RLA) for the improvement of nutraceutical properties. LIP/RLA was developed by a typical solvent injection method. Uniform liposomes of LIP/RLA were observed by transmission electron microscopy, and the mean particle size was calculated to be ∼150 nm from the data of dynamic light scattering. LIP/RLA could prevent the degradation of RLA even under acidic conditions (pH 1.2) possibly due to the encapsulation of RLA into the liposomal structure. In the release test under pH6.8 with lipase, LIP/RLA showed relatively rapid release of RLA, possibly due to the lipolysis of phospholipids by lipase. After the oral administration of LIP/RLA (10 mg-RLA/kg, p.o.) in rats, the systemic exposures of RLA and DHLA increased by 2.8- and 5.8-fold, respectively. In a rat model of acute hepatic injury induced by carbon tetrachloride (CCl4) (0.7 mL-CCl4/kg, p.o.), orally dosed LIP/RLA (3 mg-RLA/kg, p.o.) resulted in 78.7% and 86.4% reductions of plasma alanine aminotransferase, and aspartate aminotransferase, respectively; however, RLA was found to be less effective possibly due to the poor oral absorption. The RLA-loaded liposomal system might be a promising carrier for poorly water-soluble materials with poor stability under acidic conditions, as well as RLA, to improve their oral absorption and nutraceutical properties.

Correction: Sato et al. Design and Characterizations of Inhalable Poly(lactic-co-glycolic acid) Microspheres Prepared by the Fine Droplet Drying Process for a Sustained Effect of Salmon Calcitonin. Molecules 2020, 25, 1311.

The author wishes to make the following correction to this paper [...].