A liposome-based formulation containing equol, dihomo-γ-linolenic acid and propionyl-l-carnitine to prevent and treat hair loss: A prospective investigation.

Hair loss is a common aesthetic disorder that can be triggered by genetic, inflammatory, hormonal, and environmental factors acting on hair follicles and their life cycle. There are several types of hair loss that differ in causes, symptoms, and spatial and temporal progression. Androgenic alopecia, a common form of hair loss, is the consequence of a decreased microcirculation of the scalp as well as the toxic action of elevated dihydrotestosterone levels on the hair bulbs.

[Hydrating cleansing: efficacy and tolerability of new formulations with hyaluronic acid 0.2% for intimate hygiene in the woman in fertile age and menopause].

Dehydration of genital areas, known as vaginal dryness, frequently affects woman's life, from fertile to postmenopausal period, and must be treated with specific products, including proper intimate cleansing. Based on that, two new cleanser formulations, characterized by Hyaluronic Acid 0.2% as main ingredient, have been developed (Hyalo Gyn® Intimo Active and Hyalo Gyn® Intimo Advance), with the aim to provide an effective hydration of the vaginal, vulvar, perianal and anal areas beyond guaranteeing daily intimate hygiene.

A site-selective hyaluronan-interferonα2a conjugate for the treatment of ovarian cancer.

While interferon alpha (IFNα) is used in several viral and cancer contexts, its efficacy against ovarian cancer (OC) is far from being incontrovertibly demonstrated and, more importantly, is hindered by heavy systemic side effects. To overcome these issues, here we propose a strategy that allows a targeted delivery of the cytokine, by conjugating IFNα2a with an aldehyde-modified form of hyaluronic acid (HA). The resulting HA-IFNα2a bioconjugate was biochemically and biologically characterized.

Drug conjugation to hyaluronan widens therapeutic indications for ovarian cancer.

Management of ovarian cancer still requires improvements in therapeutic options. A drug delivery strategy was tested that allows specific targeting of tumor cells in combination with a controlled release of a cytotoxic molecule. To this aim, the efficacy of a loco-regional intraperitoneal treatment with a bioconjugate (ONCOFID-S) derived by chemical linking of SN-38, the active metabolite of irinotecan (CPT-11), to hyaluronan was assessed in a mouse model of ovarian carcinomatosis.

Hyaluronic Acid as a Protein Polymeric Carrier: An Overview and a Report on Human Growth Hormone.

Hyaluronic acid (HA) is a natural polysaccharide primarily present in the vitreous humor and in cartilages where it plays a key structural role in organizing the cartilage extracellular matrix. HA is used in a wide range of applications including treatment of arthritis (as a viscosupplementation agent for joints) and in a variety of cosmetic injectable products. Its safety profile is thus well established.

Peritoneal tumor carcinomatosis: pharmacological targeting with hyaluronan-based bioconjugates overcomes therapeutic indications of current drugs.

Peritoneal carcinomatosis still lacks reliable therapeutic options. We aimed at testing a drug delivery strategy allowing a controlled release of cytotoxic molecules and selective targeting of tumor cells. We comparatively assessed the efficacy of a loco-regional intraperitoneal treatment in immunocompromised mice with bioconjugates formed by chemical linking of paclitaxel or SN-38 to hyaluronan, against three models of peritoneal carcinomatosis derived from human colorectal, gastric and esophageal tumor cell xenografts.

A hyaluronic acid-salmon calcitonin conjugate for the local treatment of osteoarthritis: chondro-protective effect in a rabbit model of early OA.

Osteoarthritis (OA) is characterized by chronic degeneration of joints, involving mainly the articular cartilage and the underlying bone, and severely impairing the quality of life of the patient. Although with limited efficacy, currently available pharmacological treatments for OA aim to control pain and to retard disease progression. Salmon calcitonin (sCT) is a drug which has been shown to have therapeutic effects in experimental arthritis by inhibiting both bone turnover and cartilage degradation and reducing the activities of matrix metalloproteinases (MMP).

The role of the conformational profile of polysaccharides on skin penetration: the case of hyaluronan and its sulfates.

The literature data suggest the capacity of biomacromolecules to permeate the human skin, even though such a transdermal permeation appears to be governed by physicochemical parameters which are significantly different compared to those ruling the skin permeation of small molecules. On these grounds, the present study was undertaken to investigate the in vitro diffusion properties through the human epidermis of hyaluronic acid and their sulfates. Low- and medium-molecular-weight hyaluronic acids and the corresponding derivatives at two degrees of sulfation were then tested.

Conjugation of hyaluronan to proteins.

Polymer conjugation has been widely exploited to prolong half-life and reduce immunogenicity of therapeutic proteins. Here, the potentials of hyaluronic acid (HA) have been investigated by studying the conjugates with two model enzymes, trypsin and RNase A, and with insulin. As the direct coupling of proteins to the HA's carboxylic groups can cause cross-linking problems, a hyaluronan-aldehyde derivative has been synthesized for N-terminal site-selective conjugation.

Paclitaxel-hyaluronan hydrosoluble bioconjugate: mechanism of action in human bladder cancer cell lines.

Objectives: A previously described hydrosoluble paclitaxel-hyaluronan bioconjugate appears particularly well suited for treatment of superficial bladder cancer because of its in vitro cytotoxic profile against urothelial carcinoma (UC) cell lines and in vivo biocompatibility. The aim of this work was to assess the mechanism of action of the bioconjugate in UC cells.

Materials And Methods: Expression of CD44 and RHAMM hyaluronan-binding receptors in RT-4 and RT-112/84 UC cell lines, interaction of fluorochrome-labeled bioconjugate with tumor cells, CD44 modulation upon incubation with the compound or free hyaluronan, and caspase activation were assessed by flow cytometry.

Pharmacokinetic profile of Oncofid-S after intraperitoneal and intravenous administration in the rat.

Objectives: Oncofid-S is a bio-conjugate molecule obtained from the binding of campthotecin, SN-38, to hyaluronic acid. In view of a possible clinical development for loco-regional treatment of peritoneal carcinomatosis, this study aimed to establish the pharmacokinetic profile of Oncofid-S after single intraperitoneal or intravenous administration in the rat.

Methods: Single-dose intraperitoneal or intravenous administrations of Oncofid-S were performed.

CD44-targeting for antitumor drug delivery: a new SN-38-hyaluronan bioconjugate for locoregional treatment of peritoneal carcinomatosis.

An innovative approach for cancer therapy implies the use of drugs covalently conjugated to macromolecular carriers that specifically target molecules over-expressed on tumor cells. This drug delivery strategy may allow a controlled release of the drug and a high targeting selectivity on tumor cells, increasing drug cytotoxicity and decreasing its undesirable side effects. We provide in vitro and in vivo preclinical data on the antitumor efficacy of ONCOFID™-S, a new bioconjugate of hyaluronic acid (HA) with SN-38 (the CPT11 active metabolite), that support the validity of the drug delivery strategy implying the use of HA as macromolecular carrier of antineoplastic drugs, an approach based on the over-expression of its target CD44 (the receptor for HA-mediated motility) in a wide variety of cancers.

Synthesis, characterization and in vitro cytotoxicity studies of a macromolecular conjugate of paclitaxel bearing oxytocin as targeting moiety.

The present study describes the experimental synthetic procedure and the characterization of a new polyaspartamide macromolecular prodrug of paclitaxel, bearing oxytocin residues as targeting moieties. In vitro stability studies of bioconjugate, performed in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.

Reversibly stable thiopolyplexes for intracellular delivery of genes.

Novel polyaspartamide non-viral carriers for gene therapy were synthesized by introducing, on the same polymer backbone, positively charged groups, for electrostatic interactions with DNA, and thiol groups for the formation of disulfide bridges between polymer chains. The introduction of thiols was aimed to have a vector with low redox potential sensitivity: disulfide crosslinking in fact, being stable in extracellular environment, allowed either to have stable complexes in plasma, that can protect DNA from metabolism, or to be reduced inside the cell, where the excess of glutathion in reduced form maintains a low redox potential. The consequent destabilization of the complex after disulfide cleavage can release DNA selectively inside the cells.

Synthesis and characterization of polyaminoacidic polycations for gene delivery.

The properties as non viral gene vector of a protein-like polymer, the alpha,beta-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) were exploited after its derivatization with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) as molecule bearing a cationic group, in order to obtain stable polycations able to condense DNA. PHEA was firstly functionalized with aminic pendant groups by reaction with ethylenediamine (EDA) obtaining the alpha,beta-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide (PHEA-EDA) copolymer. We demonstrated that polymer functionalization degree is easily modulable by varying reaction conditions, so allowing to produce two PHEA-EDA derivatives at different molar percentage of amine groups.