The Uniqueness of Albumin as a Carrier in Nanodrug Delivery.

Albumin is an appealing carrier in nanomedicine because of its unique features. First, it is the most abundant protein in plasma, endowing high biocompatibility, biodegradability, nonimmunogenicity, and safety for its clinical application. Second, albumin chemical structure and conformation allows interaction with many different drugs, potentially protecting them from elimination and metabolism in vivo, thus improving their pharmacokinetic properties. Finally, albumin can interact with receptors overexpressed in many diseased tissues and cells, providing a unique feature for active targeting of the disease site without the addition of specific ligands to the nanocarrier. For this reason, albumin, characterized by an extended serum half-life of around 19 days, has the potential of promoting half-life extension and targeted delivery of drugs. Therefore, this article focuses on the importance of albumin as a nanodrug delivery carrier for hydrophobic drugs, taking advantage of the passive as well as active targeting potential of this nanocarrier. Particular attention is paid to the breakthrough NAB-Technology, with emphasis on the advantages of Nab-Paclitaxel (Abraxane), compared to the solvent-based formulations of Paclitaxel, i.e., CrEL-paclitaxel (Taxol) in a clinical setting. Finally, the role of albumin in carrying anticancer compounds is depicted, with a particular focus on the albumin-based formulations that are currently undergoing clinical trials. The article sheds light on the power of an endogenous substance, such as albumin, as a drug delivery system, signifies the importance of the drug vehicle in drug performance in the biological systems, and highlights the possible future trends in the use of this drug delivery system.

Design and evaluation of albumin nanoparticles for the delivery of a novel ß-tubulin polymerization inhibitor.

PURPOSE: The ultimate goal of this study is to develop a novel delivery system for a new potent cytotoxic compound, CCI-001, with anti-b tubulin activity, so that the drug can be effectively administered and at the same time its harmful side effects can be reduced. METHODS: In the current study, CCI-001 was loaded into serum albumin (SA), using a modified desolvation method, generating CCI-001-SA nanoparticles. Both bovine and human SA were used for the encapsulation of this drug candidate. Optimum conditions for drug loading were achieved when already formed and crosslinked albumin nanoparticles were incubated overnight at 37°C with CCI-001 solutions. The CCI-001-loaded albumin nanoparticles were assessed for average particle diameter and polydispersity, zeta potential, drug loading, in vitro release, morphology and cell toxicity against SW620 and HCT116 colorectal cancer cells. RESULTS: The spherical nanoparticles obtained were negatively charged (~ -30 mV) and had an average diameter of ~ 130 nm, with a narrow size distribution. The in vitro release of CCI-001 from the albumin nanoparticles showed a sustained release pattern over 24 hours without any initial burst release, compared to the fast release of the free drug under experimental conditions. No difference between the SA from the two species in terms of CCI-001 loading was observed. However, a significant difference was observed between the release profiles of CCI-001 from drug-loaded HSA and drug-loaded BSA nanoparticles with HSA nanoparticles showing slower drug release (mean release time, MRT, values of 5.14 ± 0.33 h and 6.88 ± 0.15 h for BSA-NPs and HSA-NPs, respectively, P < 0.01). Cellular toxicity studies showed higher cytotoxicity for CCI-001-SA compared to the free drug (IC50s of 0.62 ± 0.31 nM vs 2.06 ± 0.29 nM in SW620 cells and 0.9 ± 0.1 nM vs 4.2 ± 0.2 nM in HCT116 cells, for CCI-001-HSA NPs and free drug, respectively). Therefore, despite the low drug content level in the HSA nanoparticles of CCI-001, the formulation provides relevant concentrations for further in vivo studies in animal models due to high drug potency. CONCLUSIONS: The data support the potential use of albumin as a nanocarrier for CCI-001 in biological systems.

Modulating the Surface Properties of Lithium Niobate Nanoparticles by Multifunctional Coatings Using Water-in-Oil Microemulsions.

Inorganic nanoparticles (NPs) have emerged as promising tools in biomedical applications, owing to their inherent physicochemical properties and their ease of functionalization. In all potential applications, the surface functionalization strategy is a key step to ensure that NPs are able to overcome the barriers encountered in physiological media, while introducing specific reactive moieties to enable post-functionalization. Silanization appears as a versatile NP-coating strategy, due to the biocompatibility and stability of silica, thus justifying the need for robust and well controlled silanization protocols. Herein, we describe a procedure for the silica coating of harmonic metal oxide NPs (LiNbO3, LNO) using a water-in-oil microemulsion (W/O ME) approach. Through optimized ME conditions, the silanization of LNO NPs was achieved by the condensation of silica precursors (TEOS, APTES derivatives) on the oxide surface, resulting in the formation of coated NPs displaying carboxyl (LNO@COOH) or azide (LNO@N3) reactive moieties. LNO@COOH NPs were further conjugated to an unnatural azido-containing small peptide to obtain silica-coated LNO NPs (LNO@Talys), displaying both azide and carboxyl moieties, which are well suited for biomedical applications due to the orthogonality of their surface functional groups, their colloidal stability in aqueous medium, and their anti-fouling properties.

Primary ovarian pregnancy and its management.

Primary ovarian ectopic pregnancy, i.e., the implantation of the gestational sac in the ovary, is one of the rarest forms of ectopic pregnancy. Its incidence after natural conception ranges from 1 in 2000 to 1 in 60 000 deliveries and accounts for 3% of all ectopic pregnancies. The diagnosis is intricate and based on surgical and histopathological observations. The management is, in spite of medical improvement, based on surgery. We present a case of a 10-wk ectopic ovarian pregnancy managed laparoscopically, and we describe, through a review of the literature, the specific symptomatology, diagnostic criteria, and treatment of this particular pathology.

[Physical activity in the prevention and control of diabetes]. / L'activité physique dans la prévention et le contrôle du diabète.

Retrospective analyses in the general population habits show that regular exercise is a protection factor for the metabolic syndrome and type 2 diabetes, among many other diseases. Randomized controlled studies in at-risk population have investigated the impact of lifestyle programs, including diet and physical training, on the incidence of diabetes, confirming physical exercise as a cornerstone in the strategy of the prevention and treatment of type 2 diabetes. Although public health recommendations regarding regular physical activity are available, however often little is done by governments to implement them. Finally, the general practitioner is pivotal in counseling patients regarding their lifestyle and therefore in affecting a large number of people.

Molecular biological analysis of the heterogeneous prostate cancer group Gleason score 7.

BACKGROUND: On the basis of a multicolor-FISH test we aimed at verifying whether there is any molecular biological background for the different behavior of Gleason Score 7 prostate cancer (PCa). PATIENTS AND METHODS: Biopsies of 44 patients with histological verified PCa, 20 with Gleason score 3 + 4 (group A) and 24 with 4 + 3 (group B), were analyzed using FISH. RESULTS: In group A, FISH detected a unique gain of 8q24 in 2 patients (10.0%) and a unique loss of 8p22 in 9 patients (45.0%). No concurrent loss and gain of both sites were found in this group. Of group B (4 + 3) a unique loss of 8p22 was observed in 14 patients (58.3%) and a concurrent loss of 8p22 and gain of 8q24 in 6 patients (25.0%). CONCLUSION: Different molecular genetic patterns could explain the different biological behavior of the 2 groups. The analysis of chromosomal aberrations could therefore influence the clinical decision process in the future.