Nanocrystalline chloroxine possesses broad-spectrum antimicrobial activities and excellent skin tolerability in mice

Background: Antimicrobial submicrometer particles are being studied as promising interventions against a wide range of skin conditions, such as fungal or bacterial infections. Aims: To submicronize chloroxine, the crystalline compound 5,7-dichloro-8-hydroxyquinoline, by nanoprecipitation and characterize the resulting assemblies. Methods: The chloroxine particles were stabilized by a nonionic surfactant and were studied by a broth microdilution assay against 20 medically important bacteria and fungi. The intervention was studied using a murine model of skin irritation. Results & conclusions: Chloroxine nanoparticles with a diameter of 600–800 nm exhibit good tolerability in terms of skin irritation in vivo and good antimicrobial activity. Thus, the fabricated formulation shows great promise for interventions for both cutaneous infection control and prophylaxis.

BergaCare SmartLipids: commercial lipophilic active concentrates for improved performance of dermal products

SmartLipids are the latest generation of dermal lipid nanoparticles with solid particle matrix. Their characteristic properties resulting from the “chaotic” and disordered particle matrix structure are reviewed. These properties are high loading and firm inclusion of active agents, physical stability of the particle matrix lipid modification (primarily α, β′), and related to these three properties the improved chemical stabilization of labile active agents. Exemplarily data for these effects are shown and underlying mechanisms are discussed. Further, general properties of lipid nanoparticles, which are also exhibited by the SmartLipids, are reviewed. These include the restauration of the protective lipid skin barrier (anti-pollution effect), penetration enhancement by occlusion (invisible patch effect) and the option to control the release of active agents for optimized biological effect and reduction of side effects (e.g., skin irritation through sensitizing active agents), which improves the skin tolerability. Regulatory aspects, such as submicron particle status, excipients, and certifications, are also discussed.

A phase I dose-finding and pharmacokinetics study of CPC634 (nanoparticle entrapped docetaxel) in patients with advanced solid tumors.

3026 Background: CPC634 is a novel product with docetaxel temporarily entrapped within stabilized CriPec nanoparticles. We performed the first-in-human study with CPC634 (NCT02442531). Methods: Patients (≥18 years) received CPC634 intravenously either 3-weekly (Q3W) (part 1, 15-100 mg/m2), 2-weekly (Q2W) (part 2, 45 mg/m2) or Q3W with dexamethasone premedication (part 3) following a 3+3 design. Primary objectives were to assess safety, establish the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and to evaluate the pharmacokinetic (PK) profile of CPC634. Results: Thirty-three patients (part 1; n = 24, part 2; n = 3, part 3; n = 6) were treated. Skin toxicity was dose limiting at doses > 60 mg/m2 in part 1, and at a 45 mg/m2 dose in part 2. Skin toxicity was cumulative but resolved after ceasing treatment. The MTD in part 1 was set at 70 mg/m2. In part 3, the 60 mg/m2 was explored which resulted in improved skin tolerability even after repeated administrations without dose limiting toxicities. The RP2D was therefore set at 60 mg/m2 with dexamethasone premedication. Grade ≥3 adverse events (CTCAE version 4.03) were skin toxicity (21%), fatigue (8%), neutropenia (6%), peripheral sensory (8%) and motor neuropathy (4%), stomatitis (4%), infections (4%) and hypomagnesemia (3%). Alopecia grade 1 was reported in 15% of patients. CPC634 exhibited a dose-proportional PK profile. One partial response and sixteen cases of stable disease (RECIST 1.1) were confirmed in part 1 and in part 3 as best response. Conclusions: CPC634 could be administered safely but showed cumulative, though reversible skin toxicity at high doses. The RP2D was set at 60 mg/m2 Q3W with dexamethasone premedication. Additional studies assessing the intratumoral exposure to CPC634 (NCT0371243) and a phase II efficacy study of CPC634 in patients with platinum resistant ovarian cancer (NCT03742713) is currently ongoing. Clinical trial information: NCT02442531.