In vitro and circulation kinetic studies on π-π-stacked poly (ɛ-caprolactone)-based micelles loaded with olaparib
2024-05-22
(Press-News.org) Background and Aims
Olaparib is a selective poly (ADP-ribose) polymerase inhibitor. However, its clinical application is hindered by low solubility and undesired pharmacokinetic profiles (e.g., relatively short circulation). Therefore, the present study aims to exploit polymeric micelles as a safe solubilizer and nanocarrier of olaparib, in order to improve its solubility and pharmacokinetics.
Methods
Poly (ε-caprolactone)-co-poly (benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate), i.e., benzyl-functionalized trimethylene carbonate)-b-poly (ethylene glycol) (P(CL-co-TMC-Bz)-PEG), was synthesized by ring-opening polymerization, and used to prepare the π-π-stacked polymeric micelles for olaparib encapsulation. A series of olaparib-loaded micelles with different polymer concentrations and wt% loadings were prepared using different methods to investigate the effect of formulation variables on the size of polymeric micelles and drug loadings. In addition, the in vitro release of olaparib from the micelles, and the cytotoxicity of micellar olaparib formulations on the SKOV3 tumor cell line were evaluated by UV spectrophotometry and CCK-8 assay, respectively. Finally, the blood circulation kinetics and side effects of the incorporated olaparib in the micelles and free olaparib were investigated in SD rats using ultra-high performance liquid chromatography analysis and H&E staining, respectively.
Results
It was found that P(CL11-co-TMC-Bz5)-PEG micelles served as a safe and excellent solubilizer for olaparib, and that the solubilization capacity was easily tailored by adjusting the polymer concentration. In addition, when loaded in micelles, olaparib exhibited a sustained release behavior in vitro, and obvious cytotoxicity on SKOV3 cells. The in vivo studies revealed that olaparib incorporated in P(CL11-co-TMC-Bz5)-PEG polymeric micelles exhibited prolonged circulation (t1/2 = 2.00 hours), when compared to free olaparib (t1/2 ≤ 0.25 hours), and excellent safety. However, in terms of taking advantage of the EPR effect of the micelle delivery system to achieve the targeted olaparib delivery, the circulation time of olaparib in the micelles remained rather short.
Conclusions
The present study revealed that polymeric micelles based on P(CL11-co-TMC-Bz5)-PEG can improve the solubility of olaparib to up to 4 mg/mL in water, and that the solubilization capacity can be further improved by adjusting the polymer concentration, as needed. Therefore, P(CL11-co-TMC-Bz5)-PEG polymeric micelles can be considered as a safe solubilizer for olaparib. In addition, olaparib-loaded micelles had a good sustained release ability of olaparib in vitro, and had obvious cytotoxicity on SKOV3 cells. Furthermore, the in vivo pharmacokinetic studies revealed the prolonged blood circulation of olaparib incorporated in the micelles, when compared to free olaparib. However, in terms of taking advantage of the EPR effect of the micelle delivery system to achieve targeted olaparib delivery, the circulation time of olaparib in the micelles remained rather short. Therefore, further optimization by e.g. chemical crosslinking and drug conjugation, is needed to improve the retention of olaparib-loaded polymeric micelles in the blood circulation, and benefit from these as carriers, in order to achieve the targeted delivery of the payload in pathological tissues.
Full text
https://www.xiahepublishing.com/2996-3427/OnA-2023-00009
The study was recently published in the Oncology Advances.
Oncology Advances is dedicated to improving the diagnosis and treatment of human malignancies, advancing the understanding of molecular mechanisms underlying oncogenesis, and promoting translation from bench to bedside of oncological sciences. The aim of Oncology Advances is to publish peer-reviewed, high-quality articles in all aspects of translational and clinical studies on human cancers, as well as cutting-edge preclinical and clinical research of novel cancer therapies.
Follow us on X: @xiahepublishing
Follow us on LinkedIn: Xia & He Publishing Inc.
END
ELSE PRESS RELEASES FROM THIS DATE:
2024-05-22
Background and Aims
Clinical unmet need in managing nonalcoholic fatty liver disease (NAFLD), a common liver disorder affecting 25–30% of American adults is to develop noninvasive and robust biomarkers.
Methods
We re-measured liver AC by placing a region of interest (ROI, 3 cm tall and 3 cm wide) at 4.5 cm, 6 cm, and 7.5 cm from the skin and a large ROI (6.0 cm tall and 7.3 cm wide) on pre-recorded ATI images from 117 participants screened for NAFLD. The difference in AC value at variable ROI depths was tested using one-way ANOVA (analysis of variance). Diagnostic ...
2024-05-22
A new study – published in the Human-Animal Interactions journal – reveals that cows who are cuddled as therapy animals showed a strong preference for interactions with women when compared to men.
In turn, the research, which opens a new era on whether some therapies may be initially stronger based upon gender and not procedure, highlighted that the women also reported greater attachment behaviours towards the steers.
Dr Katherine Compitus, Clinical Assistant Professor at New York University, and Dr Sonya Bierbower, Associate Professor at United States Military Academy West Point, conducted the research using the ...
2024-05-22
I’m not touching you! When another person’s finger hovers over your skin, you may get the sense that they’re touching you, feeling not necessarily contact, but their proximity. Similarly, researchers reporting in ACS Applied Materials & Interfaces have designed a soft, flexible film that senses the presence of nearby objects without physically touching them. The study features the new sensor technology to detect eyelash proximity in blink-tracking glasses.
Noncontact sensors can identify or measure an object without directly touching it. Examples of these devices include ...
2024-05-22
Discoveries and progress in materials science often lay the foundation for technological breakthroughs that reshape many industrial and commercial fields, including medicine, consumer electronics, and energy generation, to name a few. Yet, the development of experimental techniques crucially underpins the exploration of new materials, paving the way for groundbreaking discoveries. These techniques allow scientists to delve into a material’s chemical and physical properties, unlocking insights essential for realizing their potential applications.
In a recent study ...
2024-05-22
Toronto, ON, May 22, 2024 – A new study published in the journal Psychological Medicine estimates that teens using cannabis are at 11 times higher risk of developing a psychotic disorder compared to teens not using cannabis.
This finding suggests that the association between cannabis and psychotic disorders may be stronger than indicated by previous research, which has relied largely on older data when cannabis was less potent than today. For context, the average THC potency of cannabis in Canada has increased from roughly 1% in 1980 to 20% in 2018.
Researchers from the University of Toronto, the Centre for Addiction and Mental ...
2024-05-22
Background and objectives
Patients with newly diagnosed prostate cancer (PCA) face the critical decision of whether to undergo treatment with curative intent (TCI, surgery or radiation) or conservative treatment on the background of a cancer where the potential for over-treatment and under-treatment is real. This study aimed to investigate the influence of cancer- and patient-related factors on the initial treatment decision for men with a new diagnosis of PCA and to evaluate treatment decisions against relevant guidelines.
Methods
This study undertook a retrospective ...
2024-05-22
Background and objectives
Fine needle aspiration cytology (FNAC) is a cost-efficient technique for the management of thyroid nodules. Changes in the World Health Organization classification of thyroid tumors can influence reliability of cytology. The 2023 Bethesda System for Reporting Thyroid Cytopathology has adapted cytological nomenclature to these changes. The aim of this paper was to review the management of atypia of undetermined significance (AUS) in our institution.
https://www.xiahepublishing.com/2771-165X/JCTP-2023-00062
Methods
Retrospective review of thyroid FNAC diagnosed with AUS in a single hospital between 2014 and 2022. We analyzed the management ...
2024-05-22
As much as 70% of California was covered by wildfire smoke during parts of 2020 and 2021, according to a study from the University of California, Davis. The study, published today in the journal Communications: Earth & Environment, combined lake-based sensors with satellite imagery to find that maximum smoke cover has increased by about 116,000 square miles since 2006.
The study measured lake responses to wildfire smoke in 2018, 2020 and 2021 — the three largest fire seasons on record in California. It found the lakes were exposed ...
2024-05-22
Embargoed for release: Wednesday, May 22, 2024, 5:00 AM ET
Key points:
In a large, multinational investigation of the link between extreme temperatures and stroke mortality, researchers found that of every 1,000 ischemic or hemorrhagic stroke deaths, about 11 were attributable to extreme cold and hot days.
The study also found that low-income countries bore a higher burden of heat-related hemorrhagic stroke mortality than high-income countries.
The researchers foresee an increase in fatal strokes, as well as a widening disparity ...
2024-05-22
Osaka, Japan – Part of what makes us human is our ability to think about people, places, or events that aren’t currently present—but we still don’t know exactly how our brains do this. Now, researchers from Osaka University have identified a specific kind of brain activity linked with these kinds of thoughts, such as when we daydream or let our minds wander.
When we think about things that aren’t actually happening, like when we daydream, the brain is essentially making up information rather than receiving and ...
LAST 30 PRESS RELEASES:
[Press-News.org] In vitro and circulation kinetic studies on π-π-stacked poly (ɛ-caprolactone)-based micelles loaded with olaparib
