Portable and automated analyzer for rapid and high precision in vitro dissolution of drugs

We developed a novel portable and automated dissolution test analyzer for rapid and high precision in vitro dissolution testing of drugs.The analyzer consists of a flow-through-cell drug dissolution system,an automated sequential sampling system,a high-speed capillary electrophoresis(HSCE)system,and a data acquisition system.Combining the high-temporal resolution flow-gating sampling approach with HSCE,which has outstanding advantages of efficient separation and resolution,the analyzer can achieve rapid analysis and exhibits the ability in miniaturization for on-site assessment of different active pharmaceutical ingredients.To integrate the flow-through-cell dissolution system with HSCE,a specially designed flow-gating-injection(FGI)interface was employed.The performance of the analyzer was investigated by analyzing the dissolution of immediate-release drugs including single dose(amoxicillin dispersible tablets)and fixed dose combination(amoxicillin and clavulanate potassium)drug tablets with the high-temporal resolutions of 12 s and 20 s,respectively.The dissolution profiles of different active pharmaceutical ingredients could be simultaneously and automatically monitored with high repeatability and accuracy.The analyzer was successfully utilized for the pharmaceutical quality control and bio-relevant dissolution testing,as well as in vivo-in vitro correlation analysis.Our portable analyzer is miniaturized,convenient and of low-cost,and will provide a valuable tool for dissolution testing in pharmaceutical research and development.

HIGH DOSE INTRA-ARTERIAL HEPATIC INFUSIONAL CHEMOTHERAPY WITH DRUG FILTRATION (HAI-F) FOR PRIMARY LIVER CANCER(A PRELIMINARY REPORT)

Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.

Squishy Clockwork Biobot Could Dose You with Drugs from the Inside

Soft and 3D-printed micromachines can be implanted in the body to deliver doses of a chemo drug.This strange new biobot uses neither battery nor wires,and can be controlled from outside the body to deliver a dose on command.It’s a gadget well suited for this new era of personalized medicine.

A system for determining maximum tolerated dose in clinical trial

Toxicity study,especially in determining the maximum tolerated dose(MTD)in phase I clinical trial,is an important step in developing new life-saving drugs.In practice,toxicity levels may be categorised as binary grades,multiple grades,or in a more generalised case,continuous grades.In this study,we propose an overall MTD framework that includes all the aforementioned cases for a single toxicity outcome(response).The mechanism of determining MTD involves a function that is predetermined by user.Analytic properties of such a system are investigated and simu-lation studies are performed for various scenarios.The concept of the continual reassessment method(CRM)is also implied in the framework and Bayesian analysis,including Markov chain Monte Carlo(MCMC)methods are used in estimating the model parameters.

Role of antibiotic therapy in bacterial disease：A mathematical study

Pathogenic bacteria in human system mature through the bin-synthesis of protective layer known as cell wall. This bacterial cell wall growth occurs in the presence of enzyme released by it. After maturation by the cell wall formation, pathogenic bacteria become harmful for human body as they are responsible for different diseases. Antibiotics or drugs are employed for curing bacterial diseases through the inhibition of this maturation process and it occurs by the binding progression of antibiotics with the released enzyme. But nowadays, drugs or antibiotics like β-lactum family （Amoxcillin） which are generally used for inhibition of bin-synthesis of cell wall become ineffective due to evolution of antibiotic resistance by the bacteria. Antibiotic resistance occurs when an antibiotic has lost its ability to effectively control or kill bacterial growth. As a result, the bacteria becomes ＂resistant＂ and continue to multiply for the generation of robust pathogenic bacteria in spite of drug administration. This is due to the release of another type of enzyme by the resistant bacteria which binds with the active antibiotic or drug making it ineffective. Hence, another type of drug （Clauvanic acid） is combined to resist the activity of drug hydrolyzing enzyme so that the initial drug can act effectively. Hence a combination of drug therapy is applied to cure the bacterial diseases successfully. We developed a mathematical model based on the bacterial enzyme and bacterial cell wall proliferation mechanism and showed how we can reduce the bacterial infection in the resistant cases with application of combination drugs （Amoxcillin and Clauvanic acid） to restore normal health. Based on the enzymatic activity and individual drug dynamics we studied the overall system under the single drug and combinational drug administra- tion through our formulated model analysis. We also demonstrated the different dosing time interval and dosing concentration to evaluate the optimized drug administration for arresting the cell wall formation completely. Sensitivity of the different kinetic rate constant also has been performed with subject to drug hydrolyzing enzyme. Our analytical and numerical studies also confirm the efficiency of the combinational drug treatment compared to single drug treatment being more effective in drug resistant cases providing recovery from bacterial disease.

Combination therapy using low‐dose anlotinib and immune checkpoint inhibitors for extensive‐stage small cell lung cancer

Background:This study evaluated the efficacy and safety of low‐dose anlotinib combined with immune checkpoint inhibitors as second‐line or later treatment for extensive‐stage small cell lung cancer(ES‐SCLC).Methods:The study included 42 patients with ES‐SCLC who were treated with low‐dose anlotinib combined with programmed cell death protein 1/programmed cell death‐ligand 1 inhibitors at Henan Cancer Hospital between March 2019 and August 2022.We retrospectively analyzed the efficacy and safety data for these patients.Indicators assessed included progression‐free survival(PFS),overall survival(OS),the overall response rate(ORR),the disease control rate(DCR),and adverse events(AEs).Prognostic factors were identified in univariate and multivariate analyses.Results:Median PFS was 11.0 months(95%CI:7.868–14.132)and median OS was 17.3 months(95%CI:11.517–23.083).The ORR was 28.5%and the DCR was 95.2%.Treatment‐related AEs were noted in 27 patients(64.3%),the most common of which was thyroid dysfunction(26.2%).Grade 3/4 treatmentrelated AEs were observed in two patients(4.8%).Conclusions:A combination of low‐dose anlotinib and immune checkpoint inhibitors as second‐line or later treatment for ES‐SCLC may achieve longer PFS and OS and have manageable AEs.