The effectiveness of liposomal doxorubicin hydrochloride in combination with cyclophosphan in the treatment of breast cancer in an experiment

Purpose of the study. To evaluate the antitumor efficacy of liposomal doxorubicin hydrochloride in combination with tamoxifen in the treatment of breast cancer.Materials and methods. The study included mongrel white rats (n = 30). A model of carcinogenesis (Walker 256 tumors) was created for all animals. Then we divided these rats into 3 equal groups: 1 control group (n = 10) - animals were monitored without treatment; 2 group (n = 10) - animals received neoadjuvant therapy: liposomal doxorubicin hydrochloride + cyclophosphan; 3 group (n = 10) - animals received neoadjuvant therapy with doxorubicin hydrochloride (non-liposomal) and cyclophosphan. Animals of the second and third groups received two cycles of neoadjuvant therapy. All animals were monitored for 1.5 months. We evaluated the effectiveness of antitumor therapy by measuring the size of tumors, the dynamics of their regression, and counting the number of metastases in the lungs. The toxic effects of doxorubicin hydrochloride were assessed by blood parameters: platelet and lymphocyte levels.Results. We recorded a significant inhibition of the growth of tumor nodes in the second group of rats on the 25th day from the start of the experiment compared with the first and third groups: 36004.7, 86112.1 and 38962.4 mm3, respectively. By the end of the 3rd week of the experiment, we also noted the formation of a tumor regression trend in the 2nd and 3rd groups of animals, which was reliably maintained until the end of the observation. At the end of the experiment, the number of metastases in the first group of animals was 3 times more, in the third group almost 1.5 times more than in the second (p < 0.05)Conclusion. The treatment of Walker 256 tumor with liposomal doxorubicin showed better efficacy and safety in comparison with non-liposomal doxorubicin. The tumor volume becomes smaller against the background of neoadjuvant chemotherapy with liposomal doxorubicin hydrochloride compared with its non-liposomal form, while there is no pronounced decrease in platelets and lymphocytes. We also recorded a significantly lower number of lung metastases in animals of the second group compared to other groups.

Design and characterisation of calcium carbonate microspheres for anticancer drug delivery

The development of delivery systems providing prolonged release of antitumor drugs represents one of the challenges in designing and optimization of novel tools for cancer therapy. The employment of spherical inorganic microparticles, in particular, calcium carbonate vaterite microspheres, as microcarriers appears promising because of their porous, matrix structure, biocompatibility, and biodegradability. Here, we summarize the results of the development of the approaches to synthesis of calcium carbonate vaterite microspheres with narrowed size distribution and microencapsulation of low-molecular-weight anticancer drugs, such as doxorubicin hydrochloride into obtained microspheres. Supplementing the reaction mixture with a thickener defines fabrication of homogeneous vaterite microparticles with a spherical shape and an average size of 2 to 3 μm. Synthesised microspheres ensure prolonged release of doxorubicin at physiological pH values and can be used as a delivery system and as a structural component for development of a theranostic platform for tumour treatment and diagnosis.

Irinotecan Plus Doxorubicin Hydrochloride Liposomes for Relapsed or Refractory Wilms Tumor

PurposeThe prognosis of relapsed or refractory pediatric Wilms tumor (WT) is dismal, and new salvage therapies are needed. This study aimed to evaluate the efficacy of the combination of irinotecan and a doxorubicin hydrochloride liposome regimen for relapsed or refractory pediatric WT.Patients and MethodsThe present study enrolled relapsed or refractory pediatric WT patients who were treated with the AI regimen (doxorubicin hydrochloride liposomes 40 mg/m2 per day, day 1, and irinotecan 50 mg/m2 per day with 90-min infusion, days 1–5; this regimen was repeated every 3 weeks) at Sun Yat-sen University Cancer Center from July 2018 to September 2020. The response was defined as the best-observed response after at least two cycles according to the Response Evaluation Criteria of Solid Tumors (RECIST 1.1), and toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 4.03).ResultsA total of 16 patients (male:female, 8:8) with a median age of 4.2 years (0.5–11 years) with relapsed or refractory disease were enrolled in this study, including 14 patients with relapsed disease and two patients with refractory disease. These patients received 1–8 courses (median, 3 courses) of the AI regimen. Fourteen patients were assessable for response: two with complete response (CR), five with partial response (PR), two with stable disease (SD), and five with progressive disease (PD). The objective response rate was 50% (two CR, five PR), and the disease control rate was 64% (two CR, five PR, and two SD). Seven out of 14 patients (50%) were alive at the last follow-up, ranging from 2.6 to 32.4 months. The median progression-free survival and median overall survival were 3.5 months (range 0.5–12 months) and 8 months (range 1–28 months), respectively. Sixteen patients were assessable for toxicity, with the most common grade 3 or 4 adverse events being alopecia (62%), leukopenia (40%), abdominal pain (38%), diarrhea (23%), and mucositis (16%), etc. No fatal adverse events have been observed, and modest adverse effects can be administered.ConclusionIrinotecan and doxorubicin hydrochloride liposome regimens have positive efficacy on relapsed or refractory pediatric WT with well-tolerated toxicity. A prospective clinical trial is warranted.

Optical Properties of Doxorubicin Hydrochloride Load and Release on Silica Nanoparticle Platform

Silica nanoparticles (SiO2 NPs) synthesized by the Stober method were used as drug delivery vehicles. Doxorubicin hydrochloride (DOX·HCl) is a chemo-drug absorbed onto the SiO2 NPs surfaces. The DOX·HCl loading onto and release from the SiO2 NPs was monitored via UV-VIS and fluorescence spectra. Alternatively, the zeta potential was also used to monitor and evaluate the DOX·HCl loading process. The results showed that nearly 98% of DOX·HCl was effectively loaded onto the SiO2 NPs’ surfaces by electrostatic interaction. The pH-dependence of the process wherein DOX·HCl release out of DOX·HCl-SiO2 NPs was investigated as well. For comparison, both the free DOX·HCl molecules and DOX·HCl-SiO2 NPs were used as the labels for cultured cancer cells. Confocal laser scanning microscopy images showed that the DOX·HCl-SiO2 NPs were better delivered to cancer cells which are more acidic than healthy cells. We propose that engineered DOX·HCl-SiO2 systems are good candidates for drug delivery and clinical applications.