Evaluation of oxidative stress mechanisms and the effects of phytotherapic extracts on Parkinson's disease Drosophila PINK1B9 model.

Oxidative stress is commonly observed in both idiopathic and genetic cases of Parkinson's disease (PD). It plays an important role in the degeneration of dopaminergic neurons, and it has been associated with altered telomere length (TL). There is currently no cure for PD, and extracts of antioxidative plant, such as Mucuna pruriens and Withania somnifera, are commonly used in Ayurveda to treat patients with PD. In this study, we evaluated 2 enzymatic markers of oxidative stress, glutathione (GSH) system and superoxide dismutase (SOD), and TL in a Drosophila melanogaster model for PD [phosphatase and tensin homolog-induced putative kinase 1 (PINK1)B9]. This evaluation was also performed after treatment with the phytoextracts. PINK1B9 mutants showed a decrease in GSH amount and SOD activity and unexpected longer telomeres compared with wild-type flies. M. pruriens treatment seemed to have a beneficial effect on the oxidative stress conditions. On the other hand, W. somnifera treatment did not show any improvements in the studied oxidative stress mechanisms and even seemed to favor the selection of flies with longer telomeres. In summary, our study suggests the importance of testing antioxidant phytoextracts in a PINK1B9 model to identify beneficial effects for PD.-Baroli, B., Loi, E., Solari, P., Kasture, A., Moi, L., Muroni, P., Kasture, S., Setzu, M. D., Liscia, A., Zavattari, P. Evaluation of oxidative stress mechanisms and the effects of phytotherapic extracts on Parkinson's disease Drosophila PINK1B9 model.

Beclomethasone loaded liposomes enriched with mucin: A suitable approach for the control of skin disorders.

Inflammatory skin disorders are the fourth leading cause of chronic non-fatal conditions, which have a serious impact on the patient quality of life. Due to their treatment with conventional corticosteroids, which often result in poor therapeutic efficacy, relapses and systemic side effects from prolonged therapy, these diseases represent a global burden that negatively impacts the global economy. To avoid these problems and optimize corticosteroid benefits, beclomethasone was loaded into liposome formulations specifically tailored for skin delivery. These formulations were enhanced with mucin (0.1 and 0.5 % w/v) to further ensure prolonged formulation permanence at the site of application. The addition of 0.5 % w/v mucin resulted in the formation of small unilamellar vesicles and multicompartment vesicles. Liposomes and 1mucin-liposomes were smaller (∼48 and ∼61 nm, respectively) and more monodispersed (PI ∼ 0.14 and ∼ 0.17, respectively) than 5mucin-liposomes, which were larger (∼137 nm), slightly polydispersed (PI ∼ 0.23), and less stable during storage (4 months in the dark at 25 °C). Liposomes were negatively charged (∼ -79 mV) irrespective of their composition, and capable of incorporating high amount of beclomethasone (∼ 80 %). In vitro studies on skin fibroblasts and keratinocytes confirmed the high biocompatibility of all formulations (viability ≥ 95 %). However, the use of mucin-liposomes resulted in higher efficacy against nitric oxide production and free radical damage. Finally, topical applications using 12-O-tetradecanoylphorbol-13-acetate-injured skin in vivo experiments showed that only the mucin-enriched formulations could restore healthy conditions within 4 days, underscoring promise as a treatment for skin disorders.

The imbalance of serotonergic circuitry impairing the crop supercontractile muscle activity and the mitochondrial morphology of PD PINK1B9Drosophila melanogaster are rescued by Mucuna pruriens.

Despite its great potentiality, little attention has been paid to modelling gastrointestinal symptoms of Parkinson's disease (PD) in Drosophila melanogaster (Dm). Our previous studies on standardized Mucuna pruriens extract (Mpe) have shown usefulness in the Drosophila model of PD. In this communication, we provide new information on the effect of Mpe on basal and serotonin treated contractions in the crop (i.e., an important and essential part of the gut) in Drosophila PD mutant for PTEN-induced putative kinase 1 (PINK1B9) gene. The effect of Mpe on PINK1B9 supplied with standard diet to larvae and/or adults, were assayed on 10-15 days old flies. Conversely from what we observed in the wild type flies, recordings demonstrated that exogenous applications of serotonin on crop muscles of untreated PINK1B9 affect neither the frequency nor the amplitude of the crop contraction, while the same muscle parameters are enhanced following brain injections of serotonin, thus suggesting that PINK1B9 mutants may likely have an impairment in the serotonergic pathways. Also, the mitochondrial morphology in the crop muscles is strongly compromised, as demonstrated by the transmission electron microscopy analysis. The Mpe treatment rescued the crop muscle parameters and also the mitochondrial morphology when supplied to both larvae and adults. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the gastrointestinal symptoms in PD and also confirms the useful employment of M. pruriens for PD treatment.

Hydrogels for tissue engineering and delivery of tissue-inducing substances.

This manuscript presents hydrogels (HGs) from a tissue engineering perspective being especially written for those who are approaching this field by offering a concise but inclusive review of hydrogel synthesis, properties, characterization methods, and applications.

Penetration of nanoparticles and nanomaterials in the skin: fiction or reality?

The advent of nanotechnological products in the market, while holding great promise, is raising concerns in consumers. Therefore, this contribution will attempt to compare different particulate formulations and to answer whether their passive penetration into, and potential permeation through the skin may be possible or not. To this end, skin structure, composition, and penetration paths will be concisely reviewed. Parameters generally cited to affect skin absorption will be resumed and commented on from the perspective of potentially penetrating nanosized agents. These sections will provide the basis to understand what is fiction and what is reality.

Skin absorption and potential toxicity of nanoparticulate nanomaterials.

Nanotechnology is going to change our lives in many different ways since its applications span from electronics to medical treatments. However, great concerns about nanomaterials' hazardous effects on the environment and human health are increasing as nanotechnology flourishes. Besides the benefits promoted by intentional use, worries mainly concern misuse or, worse, non-intentional exposure. In this contribution we would like to briefly summarize findings on skin penetration of nanoparticulate nanomaterials, herein indicated as nanotechnological nanoparticles, and to brain-storm on their potential ability to generate toxic effects.

From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges.

Tissue engineering is an emerging multidisciplinary field of investigation focused on the regeneration of diseased or injured tissues through the delivery of appropriate molecular and mechanical signals. Therefore, bone tissue engineering covers all the attempts to reestablish a normal physiology or to speed up healing of bone in all musculoskeletal disorders and injuries that are lashing modern societies. This article attempts to give a pharmaceutical perspective on the production of engineered man-made bone grafts that are described as implantable tissue engineering therapeutics, and to highlight the importance of understanding bone composition and structure, as well as osteogenesis and bone healing processes, to improve the design and development of such implants. In addition, special emphasis is given to pharmaceutical aspects that are frequently minimized, but that, instead, may be useful for formulation developments and in vitro/in vivo correlations.

Penetration of metallic nanoparticles in human full-thickness skin.

The potential and benefits of nanoparticles in nanobiotechnology have been enthusiastically discussed in recent literature; however, little is known about the potential risks of contamination by accidental contact during production or use. Although theories of transdermal drug delivery suggest that skin structure and composition do not allow the penetration of materials larger than 600 Da, some articles on particle penetration into the skin have been recently published. Consequently, we wanted to evaluate whether metallic nanoparticles smaller than 10 nm could penetrate and eventually permeate the skin. Two different stabilized nanoparticle dispersions were applied to excised human skin samples using vertical diffusion cells. At established time points, solutions in receiving chambers were quantified for nanoparticle concentration, and skin was processed for light transmission and electron microscope examination. The results of this study showed that nanoparticles were able to penetrate the hair follicle and stratum corneum (SC), occasionally reaching the viable epidermis. Yet, nanoparticles were unable to permeate the skin. These results represent a breakthrough in skin penetration because it is early evidence where rigid nanoparticles have been shown to passively reach the viable epidermis through the SC lipidic matrix.