BackgroundInhibitors of hyaluronidase are potent agents that maintain hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and anti-microbial agents. Sodium copper chlorophyllin complex is being used therapeutically as a component in anti-aging cosmeceuticals, and has been shown to have anti-hyaluronidase activity. In this study we evaluated various commercial lots of sodium copper chlorophyllin complex to identify the primary small molecule constituents, and to test various sodium copper chlorophyllin complexes and their small molecule analog compounds for hyaluronidase inhibitory activity in vitro. Ascorbate analogs were tested in combination with copper chlorophyllin complexes for potential additive or synergistic activity.Materials and methodsFor hyaluronidase activity assays, dilutions of test materials were evaluated for hydrolytic activity of hyaluronidase by precipitation of non-digested hyaluronate by measuring related turbidity at 595 nm. High-performance liquid chromatography and mass spectroscopy was used to analyze and identify the primary small molecule constituents in various old and new commercial lots of sodium copper chlorophyllin complex.ResultsThe most active small molecule component of sodium copper chlorophyllin complex was disodium copper isochlorin e4, followed by oxidized disodium copper isochlorin e4. Sodium copper chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase inhibitory activity down to 10 µg/mL. The oxidized form of copper isochlorin e4 disodium salt had substantial hyaluronidase inhibitory activity at 100 µg/mL but not at 10 µg/mL. Ascorbate derivatives did not enhance the hyaluronidase inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs were always the dominant components of the small molecule content of the commercial lots tested; oxidized copper isochlorin e4 was found in increased concentrations in older compared to newer lots tested.ConclusionThese results support the concept of using the hyaluronidase inhibitory activity of sodium copper chlorophyllin complex to increase the hyaluronic acid level of the dermal extracellular matrix for the improvement of the appearance of aging facial skin.

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Coenzyme Q₁₀ (CoQ₁₀) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. The aim of this research was to develop a suitable formulation for pulmonary delivery of this anticancer agent. An appropriate selection of excipients (phospholipids) and a suitable device (Aeroneb Pro® vibrating-mesh nebulizer) were selected initially after reviewing the literature. After characterization of the bulk drug, a feasible manufacturing process was selected to obtain small particle size dispersions of CoQ₁₀. Following selection of an appropriate process, the parameters affecting drug particle size were studied. Using LD and gravimetrical analysis, nebulization was evaluated to assess the performance of the inhalation system triad: drug-excipients-device. CoQ₁₀ powder studied was crystalline with a melting point approximately at 51 °C and with a particle size of 30 µm. Microfluidization was found to be a suitable method to prepare submicron drug particles in aqueous dispersions. Increasing microfluidization processing to more than 50 passes did not provide further particle downsizing for both soya phosphatidylcholine (lecithin) and dipalmitoyl phosphatidylcholine (DPPC) dispersions of CoQ₁₀, presenting Z-average values of approximately 130 and 70 nm, respectively. Nebulization performance of lecithin-stabilized CoQ₁₀ dispersions varied according to number of passes in the microfluidizer. Formulations processed with 10 passes presented steadier nebulization over time and different rheological behavior compared to those processed with 30 or 50 passes. In conclusion, aqueous dispersions of CoQ₁₀ were adequately produced using a microfluidizer with characteristics that were suitable for pulmonary delivery with an Aeroneb Pro® nebulizer. Furthermore, the rheology of these dispersions appeared to play a significant role in the aerosol generation from the active vibrating-mesh nebulizer used.

PurposeTo examine the effect of sodium copper chlorophyllin complex on the expression of biomarkers of photoaged dermal extracellular matrix indicative of skin repair.Patients and methodsFollowing a previously published 12-day clinical assessment model, skin biopsy samples from the forearms of four healthy females with signs of photoaged skin were obtained and samples were analyzed by immunohistochemistry for key biomarkers of aging skin after each subject was treated with a test material consisting of a gel containing a liposomal dispersion of sodium copper chlorophyllin complex 0.05%, a positive control of tretinoin cream 0.025%, and an untreated negative control.ResultsThere was a statistically significantly greater amount of fibrillin/amyloid P and epidermal mucins found for skin treated with the test material containing 0.05% sodium copper chlorophyllin complex and the reference control tretinoin 0.025% cream compared to the negative control (untreated site). Expression of procollagen 1 and dermal mucin also showed a greater presence in the samples treated with the test material and the reference control compared to the negative control, though the differences were not statistically significant. No adverse events were observed or reported by the subjects during the course of the study.ConclusionThe results of this human biopsy study suggest that both retinoids and sodium copper chlorophyllin complex have beneficial effects on biomarkers of photoaged skin. Products containing both sodium copper chlorophyllin complex and retinols may provide a dual approach to reversing age-related decreases in hyaluronic acid (HA) in the skin: inhibition of the breakdown of HA via sodium copper chlorophyllin complex by inhibition of hyaluronidase, and stimulation of HA synthases by retinol.

Pancreatic Carcinoma is one of the deadliest types of cancers and certainly one that is most clinically difficult to manage given that most diagnoses occur in late-stage disease. Gemcitabine is among the few FDA approved drugs used alone and in combination with other antineoplastic agents for pancreatic cancer. API 31510, a novel intravenous formulation of Ubidecarone, induced superior cell death kinetics in pancreatic carcinoma cell line, MiaPaca alone or in combination with gemcitabine. In addition, the study employed an in vivo model of pancreatic cancer to assess the translation of the cell-based data of combination gemcitabine and API 31510. Animals were randomized into 4 groups of 30 rats each; group 1 received no treatment, group 2 received gemcitabine (150 mg/kg weekly for 3 weeks with one week rest), group 3 were injected with API 31510 (50 mg/kg daily), and group 4 received a combination of daily API 31510 (50kg/mg) and gemcitabine at the aforementioned regimen. The untreated group exhibited steep death rates, whereas in API 31510, gemcitabine alone and the combination of API 31510 resulted in prolongation of life. API 31510 alone had significantly greater impact than gemcitabine alone. Animals treated with gemcitabine + API 31510 exhibited prolonged survival and elicited long-term remission that was statistically significant compared to other groups. In addition, palpable tumors were decreased in the groups treated with API 31510, and to a greater degree, in those treated with gemcitabine in combination with API 31510. It is noteworthy that tumor histology demonstrated a hallmark disruption in tumor vasculature with use if API 31510. Taken together, these findings suggest that API 31510 offers a new approach to treatment and management of pancreatic cancer alone and combination with established chemotherapy regimens that include gemcitabine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3735. doi:1538-7445.AM2012-3735