Search

[Display omitted] Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec® technology is based on amphiphilic methoxy-poly(ethylene glycol)- b -poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG- b -pHPMAmLac n) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM). Key features of CCPM are a prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in the majority of healthy tissues. Proprietary hydrolysable linkers allow for tunable and sustained release of entrapped API, including hydrophobic and hydrophilic small molecules, as well as peptides and oligonucleotides. Preclinical imaging experiments provided valuable information on their tumor and tissue accumulation and distribution, as well as on uptake by cancer, healthy and immune cells. The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models. In the clinic, CPC634 also demonstrated favorable pharmacokinetics, good tolerability, signs of efficacy, and enhanced localization in tumor tissue as compared to conventional docetaxel. PET imaging of radiolabeled CPC634 showed quantifiable accumulation in ∼50 % of tumors and metastases in advanced-stage cancer patients, and demonstrated potential for use in a theranostic setting even when applied at a companion diagnostic dose. Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG- b -pHPMAmLac n CCPM based on CriPec® technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy. [ABSTRACT FROM AUTHOR]

Objective: To assess the glycoform distribution patterns of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during the menstrual cycle at different ages and FSH levels, after menopause, and with premature ovarian failure (POF). Design: Controlled clinical study. Setting: Healthy volunteers in an academic research environment. Patient(s): Women aged 20 to 25 years with normal early follicular (EF) serum FSH (<10 IU/L), women aged 40 to 45 years with normal or increased EF serum FSH, postmenopausal women, and women with POF. Intervention(s): None. Main Outcome Measure(s): FSH and LH glycoform distributions as assessed by chromatofocusing. Result(s): In both postmenopausal and in women with POF, more acidic FSH glycoforms were found compared with young cyclic premenopausal women. In women aged 40 to 45 years with normal FSH levels, these acidic glycoform profiles already showed a statistically significant difference from the younger women. This difference was to attributable to the early follicular and luteal cycle phases. Overall, during aging and after ovarian failure, FSH becomes more acidic, a difference that is already statistically significantly detectable in premenopausal, older women before FSH rises. This is not seen for LH glycoforms. Conclusion(s): The occurrence of postmenopausal-like acidic FSH isoforms precedes the rise of FSH before menopause. [Copyright &y& Elsevier]