No abstract

The oral administration of water-soluble chemotherapeutical agents is limited by their serious gastrointestinal side effects, instability at intestinal pH, and poor absorption. Aiming to solve these problems, we chose topotecan (TPT) as a model drug and developed a novel lipid formulation containing core-shell lipid nanoparticle (CLN) that makes the water-soluble drug to 'dissolve' in oil. TPT molecules can be encapsulated into nanoparticles surrounded by oil barrier while avoiding the direct contact with intestinal environment, thus easing the intestinal hydrolytic degradation and gastrointestinal (GI) irritation. Microstructure and mean particle size of TPT-CLN were characterized by Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS), respectively. The average size of nanoparticles was approximately 60 nm with a homogeneous distribution in shapes of spheres or ellipsoid. According to in vitro stability studies, more initial form of TPT was observed in presence of lipid nanoparticle compared with free topotecan solution in artificial intestinal juice (pH 6.5). After oral administration of TPT-CLN in rats, AUC and C of TPT were all increased compared with free TPT, indicating significant enhancement of oral absorption. Intestinal lymphatic transport was confirmed as the major way for CLN to enhance oral absorption of TPT by the treatment of blocking chylomicron flow. Lower GI irritation of TPT-CLN was observed in the gastrointestinal damage studies. The in vivo antitumor activity of TPT-CLN showed an improved antitumor efficacy by oral treatment of TPT-CLN compared to free TPT. From the obtained data, the systems appear an attractive progress in oral administration of topotecan.

Intratumoral injection of anticancer drugs directly delivers chemotherapeutics to the tumor region, offering an alternative strategy for cancer treatment. However, most hydrophilic drugs spread quickly from the injection site into systemic circulation, leading to inferior antitumor activity and adverse effects in patients. Therefore, we developed novel reversed lipid-based nanoparticles (RLBN) as a nanoscale drug carrier. RLBNs differ from traditional nanoscale drug carriers in that they possess a reversed structure consisting of a polar core and lipophilic periphery, leading to excellent solubility and stability in hydrophobic liquids; therefore, hydrophilic drugs can be entrapped in RLBNs and dispersed in oil. In vivo studies in tumor-bearing Balb/c nude mice indicated remarkable antitumor activity of RLBN-DOX after a single injection, with effective tumor growth inhibition for at least 17 days; the inhibition rate was $80%. These results can be attributed to the long-term retention and sustained drug release of RLBN-DOX in the tumor region. In contrast, intratumoral injection of free DOX showed weaker antitumor activity than RLBN-DOX did, with the tumor size doubling by day 11 and tripling by day 17. Further, the initial burst of drug released from free DOX could produce detrimental systemic effects, such as weight loss. Histological analyses by TUNEL staining showed apoptosis after treatment with RLBN-DOX, whereas tumor cell viability was high in the free DOX group. Current results indicate that RLBNs show sustained delivery of hydrophilic agents to local areas resulting in therapeutic efficacy, and they may be a promising drug delivery system suitable for intratumoral chemotherapy. ARTICLE HISTORY

Transarterial chemoembolization (TACE) is a promising treatment for patients suffering from unresectable liver malignancy. A coarse emulsion of doxorubicin solution and iodized oil is widely used in clinical practice. However, this coarse emulsion lacks sufficient physical stability and can split into water and oil very quickly. Furthermore, most chemotherapeutics are quickly released into systematic circulation, causing serious adverse effects. In this study, we aimed to prepare reversed lipid-based nanoparticles (RLBNs) dispersed in iodized oil as nanocarriers for the delivery of hydrophilic chemotherapeutics. Unlike a simple mixture of drug solution and oil, RLBN is a homogenous system and possesses a hydrophobic nanostructure that has high dispersibility in oils. Hydrophilic chemotherapeutics were entrapped in the polar core juxtaposed by highly biocompatible lipid materials, such as egg phospholipids. A sustained drug-release profile was observed in both in vitro and in vivo pharmacokinetics studies. The results of computed tomography showed that RLBN–doxorubicin–iodized oil could remain in the tumor region for more than 14 days and that the growth of tumors was effectively suppressed. Thus, the current results suggest that RLBN is a promising drug delivery system and is compatible with TACE treatment.

Wuhan was the first large city where the initial breakout of COVID-19 took numerous lives. A group of social workers and mental health specialists coordinated the “Be Together Program” (BTP), a psychosocial grief intervention program to help a group of Wuhan COVID-19 bereaved people. Under the Dual-process model framework, BTP used the internet and social media as the main tools, combined with group and individual intervention. Additionally, it employed a “Supermarket Mode” with abundant intervention themes and approaches for BTP participants to choose according to their special needs. Additionally, Chinese cultural elements are integrated into the program. At the end of the program, the grief scores of participants in the qualified sample reduced significantly, and the prevalence of the potential Prolonged Grief Disorder diagnosis reduced from 75% to 12%. The study also found that the BTP was especially effective for those who had high levels of grief reaction.