[The Preventive Effect of Levofloxacin Combined with G-CSF or Only G-CSF Supportive Therapy on Infection in Autologous Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor (G-CSF) or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT), and to analyze the length of hospital stay, hospitalization cost and post-transplant survival of the patients. METHODS: A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022, the febrile neutropenia, the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed. The length of hospital stay, total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared. RESULTS: A total of 102 cases were included in this study, including 57 cases of multiple myeloma, 36 cases of acute leukaemia, 7 cases of lymphoma, 3 cases of myelodysplastic syndrome, 1 case of light chain amyloidosis, and 1 case of POEMS syndrome. 47 patients received levofloxacin+ G-CSF antibacterial prophylaxis, and 55 patients received G-CSF supportive therapy. In the levofloxacin+ G-CSF group, 40 cases (85.11%) developed febrile neutropenia, and 13 cases (27.66%) were confirmed as bacterial infection. In the G-CSF group, 44 cases (80.00%) developed febrile neutropenia, and 16 cases (29.09%) were bacterial infection. There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups (χ2=0.46，P =0.50; χ2=0.03，P =0.87). The use rate of intravenous antibiotics in the levofloxacin+ G-CSF group was 85.11% (40/47), which was not statistically different from 85.45% (47/55) in the G-CSF group (χ2=0.04，P =0.84). The detection rates of levofloxacin-resistant bacteria in the levofloxacin+ G-CSF group and G-CSF group were 8.57% (3/35) and 21.43% (6/28), respectively, with no statistical difference (χ2=0.65, P >0.05). The median length and median cost of hospitalization in the levofloxacin+ G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan, with no statistically significant differences ( t =3.00，P =0.09; t =0.94，P =0.09). Within 90 days after transplantation, two cases (4.26%) died in the levofloxacin+ G-CSF group and one case (1.82%) died in the G-CSF group, with no statistically significant difference between the two groups (χ2=0.53，P =0.47). CONCLUSION: Application of levofloxacin+ G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.

Pomalidomide improves the effectiveness of CAR-T treatment in the relapsed and refractory multiple myeloma or B-cell leukemia/lymphoma with extramedullary disease.

Relapsed and refractory multiple myeloma (RRMM) and B-cell leukemia/lymphoma with extramedullary disease (EMD) have poor prognosis and high mortality, lack of effective therapeutic approaches. We reported for the first time that 6 patients with malignant hematological diseases with EMD received chimeric antigen receptor (CAR)-T treatment combined with pomalidomide, and CAR-T cells were treated with pomalidomide in vitro to determine its killing activity and cytokine secretion. Three patients with RRMM were given B cell maturation antigen (BCMA)-CAR-T therapy. All 3 patients with B-cell leukemia/lymphoma received CD19/22-CAR-T sequential infusion. There were no treatment-related deaths. The maximum overall response rate (ORR) was 100%. Median follow-up was 211.5 days (75-407 days). Three patients (50%) experienced cytokine release syndrome, all of which were grade 1, and no neurotoxicity was observed. In vitro experiments showed that the killing activity did not differ significantly between BCMA-CAR-T cells with and without pomalidomide (10, 25, or 50 µg/mL) in 8226/U266 cell cocultures (P > .05). Tumor necrosis factor (TNF)-α and interferon (IFN)-γ secretion was significantly higher from 8226 and Raji cells cocultured with BCMA-CAR-T and cluster of differentiation (CD)19-CAR-T cells (P < .05). Based on the cocultures, adding pomalidomide significantly promoted IFN-γ and TNF-α secretion (P < .05). Based on the above clinical and in vitro studies demonstrating the co-administration of pomalidomide with CAR-T cell treatment demonstrated favorable tolerability and therapeutic effectiveness in RRMM or B-cell leukemia/lymphoma.

Peripheral Blood Smears Distinguish Infective Fever after CAR-T Therapy.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy carries the risk of inducing severe and life-threatening toxicities such as cytokine release syndrome (CRS), neurotoxicity, and infection. Although CRS and infections have similar symptoms, their treatment strategies differ, and early diagnosis is very important. For CRS and infections, the fastest detection time currently takes more than 24 h, so a quick and simple method to identify a fever after CAR T-cell infusion is urgently needed. METHODS: We enrolled 27 patients with recurrent fever treated with different types of CAR T-cells, including cluster of differentiation (CD) 7, CD19, CD22, and CD19-CD22 bicistronic CAR T-cells, and evaluated the infection events occurring in these patients. We detailed the morphology of CAR T-cells in peripheral blood smears (PBS) and reported the infection events, CAR transgene copy number, and inflammatory indicators within the first month after treatment. RESULTS: Similar morphological characteristics were observed in the PBS of different CAR T-cells, namely, enlarged cell bodies, deep outside and shallow inside basophilic blue cytoplasm, and natural killer (NK) cell-like purplish red granules. There were ten infections in nine of the twenty-seven patients (33%). The percentage of atypical lymphocytes in PBS was significantly associated with CAR transgene copy number and absolute lymphocyte count in all patients. The atypical lymphocyte percentage was significantly higher in the non-infection group. CONCLUSIONS: In conclusion, the unique morphology of CAR T-cells in PBS can be used to evaluate CAR T-cell kinetics and provide reliable evidence for the rapid early identification of fever after CAR T-cell infusion. CLINICAL TRIAL REGISTRATIONS: ChiCTR-OPN-16008526; ChiCTR-OPN-16009847; ChiCTR2000038641; NCT05618041; NCT05388695.

Plasmacytoid dendritic cell expansion in myeloid neoplasms: A novel distinct subset of myeloid neoplasm?

Plasmacytoid dendritic cells (pDCs) are a specific dendritic cell type stemming from the myeloid lineage. Clinically and pathologically, neoplasms associated with pDCs are classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN), mature plasmacytoid dendritic myeloid neoplasm (MPDMN) and pDC expansion in myeloid neoplasms (MNs). BPDCN was considered a rare and aggressive neoplasm in the 2016 World Health Organization (WHO) classification. MPDMN, known as mature pDC-derived neoplasm, is closely related to MNs and was first recognized in the latest 2022 WHO classification, proposing a new concept that acute myeloid leukemia cases could show clonally expanded pDCs (pDC-AML). With the advances in detection techniques, an increasing number of pDC expansion in MNs have been reported, but whether the pathogenesis is similar to that of MPDMN remains unclear. This review focuses on patient characteristics, diagnosis and treatment of pDC expansion in MNs to gain further insight into this novel and unique provisional subtype.

Lack of surgical resection is associated with increased early mortality in hematological patients complicated with rhino-orbital-cerebral mucormycosis.

Rhino-orbital-cerebral mucormycosis (ROCM), which is an acute fatal infectious disease with a high mortality rate, is increasingly being diagnosed in patients with hematological diseases worldwide. We aimed to investigate the clinical characteristics, treatment, and prognosis of hematological diseases complicated by ROCM. Our sample comprised a total of 60 ROCM patients with hematological diseases. The most common primary disease was acute lymphoblastic leukemia (ALL) (n=27, 45.0%), while 36 patients (60.0%) were diagnosed with a clear type of pathogen, all belonging to the Mucorales, most commonly Rhizopus (41.7%). Of the 32 patients (53.3%) who died, 19 (59.3%) died of mucormycosis, and 84.2% (n=16) of those died within 1 month. Forty-eight cases (80.0%) received antifungal treatment combined with surgical therapy, 12 of whom (25.0%) died of mucormycosis, amounting to a mortality rate that was significantly lower than in patients who received antifungal therapy alone (n=7, 58.3%) (P=0.012). The median neutrophil value of patients who underwent surgery was 0.58 (0.11-2.80) 103/µL, the median platelet value was 58.00 (17.00-93.00) 103/µL, and no surgery-related deaths were reported. Multivariate analysis showed that patient's advanced age (P=0.012, OR=1.035 (1.008-1.064)) and lack of surgical treatment (P=0.030, OR=4.971 (1.173-21.074)) were independent prognostic factors.In this study, hematological diseases associated with ROCM have a high mortality rate. Lack of surgical treatment is an independent prognostic factor for death from mucormycosis. Surgery may therefore be considered in patients with hematological disease even if their neutrophil and platelet values are lower than normal.

Multidisciplinary recommendations for the management of CAR-T recipients in the post-COVID-19 pandemic era.

The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.

Simultaneous quantification of pirarubicin, doxorubicin, cyclophosphamide, and vincristine in human plasma of patients with non-Hodgkin's lymphoma by LC-MS/MS method.

Pirarubicin (THP), doxorubicin (DOX), cyclophosphamide (CTX), and vincristine (VCR) are widely used in the treatment of patients with non-Hodgkin's Lymphoma. Herein, a precise and sensitive method was developed for the determination of THP, DOX, CTX and VCR in human plasma by high-performance liquid-chromatography-tandem mass spectrometry (LC-MS/MS). Liquid-liquid extraction was applied to extract THP, DOX, CTX, VCR, and the internal standard (IS, Pioglitazone) in plasma. Agilent Eclipse XDB-C18 (3.0 mm × 100 mm) was utilized and chromatographic separation was obtained in eight minutes. Mobile phases were composed of methanol and buffer (10 mM ammonium formate containing 0.1% formic acid). The method was linear within the concentration range of 1-500 ng/mL for THP, 2-1000 ng/mL for DOX, 2.5-1250 ng/mL for CTX, and 3-1500 ng/mL for VCR. The intra- and inter-day precisions of QC samples were found to be below 9.31 and 13.66%, and accuracy ranged from -0.2 to 9.07%, respectively. THP, DOX, CTX, VCR and the internal standard were stable in several conditions. Finally, this method was successfully utilized to simultaneously determine THP, DOX, CTX and VCR in human plasma of 15 patients with non-Hodgkin's Lymphoma after intravenous administration. Finally, the method was successfully employed in the clinical determination of THP, DOX, CTX, and VCR in patients with non-Hodgkin lymphoma after administration of RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens.

[Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model. METHODS: The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established. RESULTS: 164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 µmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285). CONCLUSION: Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.

Eastern Cooperative Oncology Group, ß2-microglobulin, hemoglobin, and lactate dehydrogenase can predict early grade ≥ 3 infection in patients with newly diagnosed multiple myeloma: A real-world multicenter study.

Introduction: This research explored the clinical application of grade ≥ 3 infection predictive models for the newly diagnosed multiple myeloma (NDMM) population. Methods: It evaluated 306 patients with NDMM based on three different predictive models. The relationship between the grade ≥ 3 infection rates in NDMM and the scores was analyzed retrospectively. The cumulative incidence of early grade ≥ 3 infection was estimated using the Kaplan-Meier method and log-rank test to assess the statistical significance of the difference. To compare the predictive performance in the prediction of infection, the Receiver Operating Characteristic Curve (ROC) curve was used to show the area under the curve (AUC), and DeLong's test was used to analyze the difference in AUC. Results: The incidence of grade ≥ 3 infection within the first 4 months of NDMM was 40.20%. Concerning the FIRST score (predictors: ECOG, ß2-microglobulin, hemoglobin, and lactate dehydrogenase), GEM-PETHEMA score (predictors: albumin, male sex, ECOG, and non-IgA type MM), and Infection Risk model of Multiple Myeloma (IRMM) score (predictors: ECOG, serum ß2-microglobulin, globulin, and hemoglobin), the probability of early grade ≥ 3 infection in the different groups showed statistically significant differences (low-risk vs. high-risk: 25.81% vs. 50.00%, p < 0.001; low-risk vs. moderate-risk vs. high-risk: 35.93% vs. 41.28% vs. 60.00%, p= 0.045; low-risk vs. moderate-risk vs. high-risk: 20.00% vs. 43.75% vs. 52.04%, p < 0.001). Statistical differences existed in the probability of early grade ≥ 3 infection among the different groups by the FIRST and IRMM scores but no statistical differences in the GEM-PETHEMA score (p < 0.001, p< 0.001, and p = 0.090, respectively). The FIRST score showed good discrimination and simple calculation with highest AUC. Further subgroup analysis showed that the FIRST score could still apply for patients treated with bortezomib-based regimen and frail patients. Discussion: Our findings indicate that the FIRST score (consisting of ECOG, ß2-microglobulin, hemoglobin, and lactate dehydrogenase) is a simple and robust infection stratification tool for patients with NDMM and could be used in routine clinical work.

Carfilzomib inhibits the proliferation and apoptosis of multiple myeloma cells by inhibiting STAT1/COX-2/iNOS signaling pathway.

Background: The ubiquitin-proteasome pathway (UPP) plays a key role in the intracellular degradation of abnormal and misfolded proteins in eukaryotic cells. Multiple myeloma (MM) is a common hematologic malignancy caused by clonal expansion of malignant plasma cells. Proteasome-targeted drugs such as carfilzomib, which is a selective proteasome inhibitor (PI), could play an important role in the treatment of diseases such as MM. Methods: MM cells were treated with different concentrations of carfilzomib and apoptosis as well as the viability of MM cells were measured by flow cytometry analysis and MTT assay. We also measured the effect of carfilzomib on the proliferation of myeloma cells by DNA incorporation of the pyrimidine analog BrdU. The effect of carfilzomib on apoptosis was detected by immunofluorescence TUNEL staining and western blot. We also verified its effect on the STAT1/COX-2/iNOS pathway by western blot. Results: Carfilzomib inhibited the growth of MM cells in a concentration-dependent manner, with the strongest inhibitory activity on RPMI-8226 cells. Carfilzomib also induced apoptosis of MM cells in a concentration-dependent manner, with the strongest effect on RPMI-8226. BrdU assay was then performed with RPMI-8226 cells, and the results showed that carfilzomib inhibited cell proliferation in a concentration-dependent manner. Immunofluorescence TUNEL staining and western blot assays showed that carfilzomib induced apoptosis in a dose-dependent manner, and promoted the expression of apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-3, Bax and Bcl2. Western blot also verified that carfilzomib promoted STAT1 inhibition and subsequently inhibited COX-2 and iNOS. Conclusions: Inhibition of the STAT1/COX-2/iNOS signaling pathway by carfilzomib not only inhibited MM cell proliferation, but was also an important mechanism of inducing MM cell apoptosis.

Anti-BCMA CAR-T Cell Therapy in Relapsed or Refractory Multiple Myeloma Patients with Impaired Renal Function.

Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy is effective and well-tolerated for refractory or relapsed multiple myeloma (RRMM). The purpose of the present study was to analyze efficacy in RRMM patients with renal impairment treated by anti-BCMA CAR-T cell therapy. A total of 59 RRMM patients were selected, and divided into impaired renal function (IRF) group [baseline estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (n=18)] and normal renal function (NRF) group (baseline eGFR ≥ 90 mL/min/1.73 m2, n=41). For patients with IRF, eGFR at the 6th month post-CAR-T cells infusion was significantly higher than the baseline (P<0.05). The multivariate analysis showed that light chain type and beta-2 micro-globulin (beta-2M) were associated factors with the decrease of serum creatinine. Median progression-free survival (PFS) in the NRF group and IRF group was 266 days and 181 days respectively. Overall survival (OS) in the NRF group and IRF group was 877 days and 238 days respectively. There was no significant difference in the objective response rate (ORR) between the IRF group and the NRF group. It is suggested that CAR-T cells therapy could improve the renal function during the treatment of RRMM. The renal function could be more significantly improved in RRMM patients with light chain type than with other types.

Hepatic targeting of glycyrrhetinic acid via nanomicelles based on stearic acid-modified fenugreek gum.

This study aimed to increase the solubility of glycyrrhetinic acid (GA) in water and enhance its liver-targeting ability using self-assembling nanomicelles (NMs) based on stearic acid-modified fenugreek gum (FG-C18). The GA/FG-C18 NMs were prepared by an ultrasonication dispersion method. The nanomicelles were spherical particles with a particle size of 198.61 ± 1.58 nm and a zeta potential of -30.12 ± 0.28 mV. The drug loading and encapsulation efficiency were 13.34 ± 0.24% and 80.07 ± 1.44%, respectively. The results of differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) indicated that GA was successfully encapsulated into the nanomicelles in a molecularly dispersed state. An in vitro release test showed that GA/FG-C18 NMs possessed a slow drug release profile in PBS (pH 7.4) over 200 h. The cytotoxicity assay indicated that GA/FG-C18 NMs showed much higher inhibitory efficacy in HepG2 cells than in MCF-7 cells. Tissue section studies indicated that the accumulation of DiR-loaded FG-C18 nanomicelles in the liver of mice was higher than that of the DiR solution, and the fluorescence intensity decreased over time. GA/FG-C18 NMs showed a larger area under the curve (AUC) and mean residence time (MRT) compared with free GA after intravenous administration in mice. The in vivo studies showed that GA mainly accumulated in the liver after encapsulation by FG-C18 NMs, and the drug concentration was higher than that of free GA. These results suggested that FG-C18 NMs could serve as a potential drug delivery system for targeting GA to liver tissue.

Synthesis and evaluation of hydrophobically modified fenugreek gum for potential hepatic drug delivery.

The objective of this study was to hydrophobically modify fenugreek gum (FG) and to further evaluate the potential application of the obtained derivative in liver-targeted drug delivery system. Stearic acid (C18) was conjugated with FG (FG-C18) by a simple esterification reaction. The obtained FG-C18 was then characterized on its chemical structure by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The self-assembled nanomicelles (NMs) of FG-C18 in water were prepared by an ultrasonication method. The average diameter and zeta potential of FG-C18 NMs were 196.70 ± 6.12 nm and -31.79 ± 1.58 mV, respectively. FG-C18 NMs appeared as spherical particles under transmission electron microscopy and possessed a critical micellar concentration of 0.042 mg/ml by pyrene fluorescence probe method. A low toxicity of FG-C18 was revealed on both HepG2 and MCF-7 cells at 0.1-100 mg/ml. Haemolysis of FG-C18 was less than 5%. Cellular uptake of coumarin-6 into HepG2 cells was enhanced by treating with C6-loaded FG-C18 NMs compared to free coumarin-6. These results suggest that FG-C18 have a potential application for a liver targeted drug delivery.

Synthesis, self-assembly, and in vitro toxicity of fatty acids-modified Bletilla striata polysaccharide.

Hydrophobic modification of Bletilla striata polysaccharide (BSP) was performed by grafting fatty acids to BSP backbone and then characterized on their physicochemical properties. All neutral derivatives were able to self-assemble into spherical particles within the size range of 250-400 nm, their size and critical micelle concentration decreased with increasing hydrophobicity and substitution degree of the fatty acids. Also, the BSP-stearic acid conjugates showed a preferable performance on hemolysis test and cytotoxicity analysis on HepG2 cells, which suggested their potential application as a drug delivery vector.

Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting.

Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver.

Microenvironmental pH-modified solid dispersions to enhance the dissolution and bioavailability of poorly water-soluble weakly basic GT0918, a developing anti-prostate cancer drug: preparation, characterization and evaluation in vivo.

The aim of the present work was to design a pH-modified solid dispersion (pH(M)-SD) that can improve the dissolution and bioavailability of poorly water-soluble weakly basic GT0918, a developing anti-prostate cancer drug. To select the appropriate acidifiers, a solubility test was carried out first. Solid dispersions (SDs) containing GT0918 and polyvinylpyrrolidone (PVP) were prepared using a solvent evaporation method and were characterized using dissolution studies in different media. The solid states of the SDs were investigated using scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transformed infrared spectroscopy (FTIR). The in vivo pharmacokinetics of the pH(M)-SDs tablets were also studied in beagle dogs compared to the conventional tablets. The optimized pH(M)-SD (GT0918/PVP/citric acid, 1:2:2 weight ratio) exhibited a significant improvement in the dissolution behavior compared to both the physical mixture and the binary SDs. Solid-state characterization revealed that the amorphous formation of GT0918 in the SDs and the strong H-bonding were only found in the pH(M)-SDs containing citric acid. Furthermore, the GT0918-loaded pH(M)-SD tablets showed a higher AUC and a lower tmax compared to the conventional tablets. Accordingly, the pH(M)-SD might be an efficient route for enhancing the dissolution and bioavailability of poorly water-soluble GT0918.