Studies on the skin penetration mechanisms of liposomal formulations

Liposomes have also been shown to enhance the penetration of a variety of drugs in the skin. When drug substances are applied on the skin in solution form, drug penetration mainly depends on the physicochemical properties of the drug however, incorporation of drugs in the liposomes results in a rather complex interaction between the stratum corneum, phospholipid membrane and drug. Studies in this thesis were designed to probe the interactions between the stratum corneum and invasomes in order to gain a better understanding of the mechanisms involved in the drug delivery to skin from invasomes. Confocal Raman microscopy was employed to study the co-diffusion of liposomally entrapped drugs and the phospholipids forming the liposomal bilayers. The study was based on a premise that if diffusion patterns of both, drug and phospholipid could be studied in the skin then it might allow us to comment on the underlying mechanism responsible for penetration of drug as each mechanism should give rise to a different diffusion profile. A method was developed to obtain non-invasive Raman depth profiles in ex vivo human skin. Optical biopsies of untreated skin were measured along with diffusion profiles of skin treated with beta-carotene and deuterated water. Tip-enhanced Raman scattering (TERS) was the tool of choice as TERS is not limited by the Abbe’s resolution limit and is an excellent tool for providing chemical and structural information. Conventional tape stripping technique was adopted to allow application of TERS. In vivo human skin was treated with deuterated invasomes and the stratum corneum was progressively removed. TERS and atomic force microscopy measurements revealed that intact invasome vesicles did penetrate the stratum corneum. For the first time spectroscopic evidence along with high resolution imaging confirmed that intact liposomes can penetrate the human stratum corneum

Stimulating brain recovery after stroke using theranostic albumin nanocarriers loaded with nerve growth factor in combination therapy

For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter the central nervous system. In the present study, nerve growth factor and ultrasmall particles of iron oxide were co-encapsulated into a chemically crosslinked albumin nanocarrier matrix which was modified on the surface with apolipoprotein E. These biodegradable nanoparticles with a size of 212 ± 1 nm exhibited monodisperse size distribution and low toxicity. They delivered NGF through an artificial blood brain barrier and were able to induce neurite outgrowth in PC12 cells in vitro. In an animal model of stroke, the infarct size was significantly reduced compared to the vehicle control. The combination therapy of NGF and the small-molecular MEK inhibitor U0126 showed a slight but not significant difference compared to U0126 alone. However, further in vivo evidence suggests that successful delivery of the neuropeptide is possible as well as the synergism between those two treatments

Nanomaterials - Tiny particles and big challenges

After decades of research, nanotechnology has been used in a broad array of biomedical products including medical devices, drug products, drug substances, and pharmaceutical-grade excipients. But like many great achievements in science, there is a fine balance between the risks and opportunities of this new technology. Some materials and surface structures in the nanosize range can exert unexpected toxicities and merit a more detailed safety assessment. Regulatory agencies such as the United States Food and Drug Administration or the European Medicines Agency have started dealing with the potential risks posed by nanomaterials. Considering that a thorough characterization is one of the key aspects of controlling such risks this review presents the regulatory background of nanosafety assessment and provides some practical advice on how to characterize nanomaterials and drug formulations. Further, the challenges of how to maintain and monitor pharmaceutical quality through a highly complex production processes will be discussed.JRC.F.2-Consumer Products Safet