Reexamining the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin.

Higher drug loading employed in nanoscale delivery platforms is a goal that researchers have long sought after. But such viewpoint remains controversial because the impacts that nanocarriers bring about on bodies have been seriously overlooked. In the present study we investigated the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin (PLD). We prepared PLDs with two different drug loading rates: high drug loading rate, H-Dox, 12.9% w/w Dox/HSPC; low drug loading rate, L-Dox, 2.4% w/w Dox/HSPC (L-Dox had about 5 folds drug carriers of H-Dox at the same Dox dose). The pharmaceutical properties and biological effects of H-Dox and L-Dox were compared in mice, rats or 4T1 subcutaneous tumor-bearing mice. We showed that the lowering of doxorubicin loading did not cause substantial shifts to the pharmaceutical properties of PLDs such as in vitro and in vivo stability (stable), anti-tumor effect (equivalent effective), as well as tissue and cellular distribution. Moreover, it was even more beneficial for mitigating the undesired biological effects caused by PLDs, through prolonging blood circulation and alleviating cutaneous accumulation in the presence of pre-existing anti-PEG Abs due to less opsonins (e.g. IgM and C3) deposition on per particle. Our results warn that the effects of drug loading would be much more convoluted than expected due to the complex intermediation between nanocarriers and bodies, urging independent investigation for each individual delivery platform to facilitate clinical translation and application.

In vivo delivery process and regulating mechanisms of lipid-based nanomedicines / 药学学报

Lipid-based nanocarrier is a classic drug delivery system with great biocompatibility and biodegradability. It can effectively reduce the toxicity of anti-tumor and anti-infective drugs in clinical practice. However, it has not yet met the clinical demand for enhanced therapeutic efficacy, and the clinical application is still very limited. The complex in vivo delivery process of lipid-based nanomedicine and the reciprocal interactions with body lead to unexpected changes in in vivo performance of nanomedicine and seriously hinder clinical translation. Therefore, the in-depth study of the relationships among intrinsic properties of lipid-based nanomedicine, the in vivo delivery process, and the regulatory mechanisms will not only provide guidance for the rational design of nanocarriers, but also promote the clinical translation and precision medicine of new lipid-based nanomedicine. In this review, we summarize the in vivo delivery process, regulating factors and intervention strategies for the in vivo delivery of lipid-based nanomedicine.

Clinicopathological Significance of AKT1 and PLK1 Expression in Oral Squamous Cell Carcinoma.

Purpose: Oral squamous cell carcinoma (OSCC) is the sixth leading cause of cancer-related death worldwide and is characterized by metastasis and recurrence. We aimed to evaluate the expression of AKT1 and PLK1 in OSCC and identify their correlation with the clinical and histological features and prognosis of patients with OSCC. Methods: Tissue samples were collected from 70 patients with OSCC and 50 patients with normal oral mucosa. The expression levels of AKT1 and PLK1 in OSCC tissues and normal oral mucosa were detected by immunohistochemistry. The chi-square test was used to identify correlations between the expression levels of AKT1 and PLK1 with patients' clinicopathologic characteristics. Survival analysis was assessed by the Kaplan-Meier method. Spearman's rank correlation test was used to determine the relationships between AKT1 and PLK1 expressions. The bioinformatics database GEPIA was used to verify the experimental results. Results: The chi-square test and Fisher's exact test showed that the positive expression rate of AKT1 and PLK1 in OSCC tissue was significantly higher than that in the normal oral mucosa (P < 0.05). PLK1 expression levels were significantly correlated with tumor stage and size (P < 0.05). Kaplan-Meier analysis showed that the survival time of AKT1 and PLK1 with high expression was significantly shorter than that of patients with low expression (P < 0.05). Spearman's rank correlation test showed a strong correlation between AKT1 and PLK1 expression in OSCC tissue (R = 0.53; P < 0.05). GEPIA bioinformatics database analysis results show that the expression and overall survival of AKT1 and PLK1 analysis and the correlation analysis of AKT1 and PLK1 were consistent with experimental results. Conclusion: AKT1 and PLK1 expressions are associated with the occurrence and progression of OSCC and may be used as diagnostic and prognostic indicators of OSCC. There may be a correlation between AKT1 and PLK1 in OSCC tissue.

Comparison of submucosal resection and radiofrequency turbinate volume reduction for inferior turbinate hypertrophy: evaluation by magnetic resonance imaging.

Inferior turbinate hypertrophy is a frequent cause of nasal airway obstruction and drastically impairs patients' quality of life. Surgical reduction of the inferior turbinates can be used for patients who did not respond to medical therapy. A number of studies have been performed to identify the most effective technique. The aim of this study was to compare the effectiveness of submucosal resection (SMR) and radiofrequency turbinate volume reduction (RFTVR) in patients with inferior turbinate hypertrophy. A prospective, randomized case-control study was conducted. Sixty patients with inferior turbinate hypertrophy refractory to medical therapy were prospectively and randomly assigned to two groups: SMR and RFTVR. A visual analog scale (VAS) and the nasal inspiratory peak flow (NPIF) were analyzed pre- and postoperatively at the first week and second month. Magnetic resonance imaging was performed pre- and postoperatively at the second month. The surgical outcomes were compared statistically using subjective and objective measures. Significant turbinate volume reduction was achieved in both the SMR and RFTVR groups. However, turbinate volume reduction was significantly greater in the SMR than in the RFTVR group at the second month postoperatively. NIPF and VAS scores were improved after both procedures at the second month postoperatively. Beside this, surgical outcomes were significantly better after SMR in terms of NIPF and VAS scores. In this study, we demonstrated that both SMR and RFTVR are effective for inferior turbinate hypertrophy. Turbinate volume reduction, improvement of subjective nasal obstruction symptoms, and NIPF after SMR were significantly superior to those after RFTVR.