The Formulation of a Bone Targeted Drug Delivery System of Poly(Glycolic Acid)-Poly(Ethylene Glycol) Coated Hydroxyapatite Nanoparticles for the Delivery of Statins

Bone is a form of mineralized connective tissue that provides strength and rigidity to the skeleton. The two primary components within bone tissue are an organic extracellular matrix, containing type I collagen, and an inorganic mineral component composed mainly of calcium phosphate hydroxyapatite crystals. Over time the microarchitecture of bone can break down due to a variety of different factors, mainly the onset of osteoporosis in post-menopausal women, Paget\u27s disease, and the experience of a loss of gravity during space flight. Currently there are about ten million people in the United States alone suffering from osteoporosis. The prevention of further damage as well as the replacement of lost bone tissue is the focus of many therapeutic approaches. A large number of available treatments rely on the concept of blocking further bone loss by inhibiting the natural resorption process. Bisphosphonates are the most popular drug therapy in this category. But there are many other treatments that strive to prevent further bone resorption such as hormone therapy, estrogen agonist / antagonists, calcitonin, and denosumab. Other therapies approach the problem of bone loss by inducing the formation of new bone tissue to replace that lost to these pathologies. These include teriparatide, strontium ranelate, and statins, which are the focus of this research. The goal of this research was to formulate a targeted nanoparticle drug delivery system for the treatment of bone diseases. A hydroxyapatite nanoparticle conjugated with poly(glycolic acid)-poly(ethylene glycol) diblock copolymer was created to deliver statin drugs. These drugs act as competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, for the lowering of serum cholesterol. Recently, statins have been investigated for their ability to induce bone formation by enhancing expression of bone morphogenic protein-2. In addition to formulation, studies were completed to prove the particle\u27s low toxicity, loading abilities, and release pharmacokinetics. In order to enhance the specificity with which these particles are delivered to bone, targeting peptides were tested for in vitro and in vivo targeting efficiency and exclusivity

L’uso della forza nelle relazioni tra gli stati: teoria ed evoluzioni nella prassi geo-politica

The use of force in interstate relations: theory and evolutions in geo-political practice. – The use of force in relations between states and other players on the world stage: theory, practice and developments in political geography. Based on the experiences of the twentieth century (world wars, genocides, ideological-totalitarian degenerations, de-colonization processes), the geopolitical thought of late modernity, starting from the 1960s, essentially develops in a “critical” sense. Then it assumes, among its favorite themes, the discussion on the essence of power (whether or not it is intrinsically “bad”), of the state and of politics (if they inevitably have to rely on the use of force); then it starts the development of a method targeted to regulation and prevention of conflicts, based on a process of deconstruction of alleged “false” ideas of power, to prevent the effects of escalation that have led the whole of humanity to the risk of destruction and self-destruction. These needs are translated operationally into the search for the so-called “insider” factors, that is, those that, in a certain scenario, beyond an immanent and self-evident “casus belli”, cause effects of permanent and out of control conflict, to the point of making war an element that justifies itself (an end, rather than a means). Effects that confuse any causal chain, which make it difficult to identify links and motivations, and therefore the search for a solution, and with it the pacification of crisis scenarios (which in fact tend to perpetuate themselves in areas of “endemic” conflictuality. All this proceeding on the basis of a neo-Enlightenment (possibly neo-liberal) assumption, which almost deterministically assumes the affirmation of an open society, refractory to violence, and the assimilation of “evil” to the mechanisms of democratization, to open market and capitalist prosperity. All this in a context of multilateral policy development, the establishment of international organizations, and the consolidation of a trans-national geo-economic apparatus, of civil society as an “answer to war”, with the aim of progressively limiting, up to cancel the same occasions of conflict; and this to the point that an idea of war as something obsolete spreads (perhaps in an illusory way). The latest events, however, and recent developments, seem to contradict this trend, re-proposing themes and tensions that geographic-political theory seemed to have abandoned for some time. A fact made even more evident by the current invasion of Ukraine, which leaves you dismayed, like aggression to troglodytic times, when the invasion did not need to have a justification; it seems to cause deliberate violence and destruction on a large scale, so much so as to question the entire “critical” paradigm. Putin 24th February discourse deliberately denies the right of Ukraine to survive as a national human community. Evolutions that make it necessary to rethink the practices of limitation and regulation, of the intervention and prevention devices of war, and of the same method of study of the scenarios; perhaps a return to models that, just until a few months ago, were considered outdated

Od industrijskega distrikta do industrijske simbioze: Priložnost. Primer industrijskega območja Ponte Rosso, Italija

The article highlights the importance of industrial symbiosis in the industrial ecology literature, which refers to geographically close relationships between companies in which networks and geographic proximity play a vital role. Industrial symbiosis traditionally deals with different industries in a collective approach to economic and environmental management. The research was carried out in the northeast of Italy in the autonomous region of Friuli Venezia Giulia, close to the Slovenian border. The Ponte Rosso was used as a case study. The empirical analysis served to highlight some critical aspects of the environmental, geographic-economic, and social factors that could hinder the development of industrial symbiosis in this regionČlanek prikazuje pomen bistvenega pojava v literaturi o industrijski ekologiji, ki označuje geografsko tesne odnose med podjetji, v katerih igrajo omrežja in geografska bližina ključno vlogo – industrijske simbioze. Ta se tradicionalno ukvarja z ločenimi panogami v skupnem pristopu poslovanja in ravnanja z okoljem. Raziskava je bila izvedena na severovzhodu Italije v Avtonomni deželi Furlaniji Julijski krajini, v neposredni bližini slovenske meje. Ponte Rosso je bil vzet kot primer, za katerega so značilne priznane okoljske, geografske, gospodarske in družbene koristi. Z empirično analizo izpostavljamo nekatere ključne vidike okoljskih, geografsko-ekonomskih in družbenih dejavnikov, ki so ovira razvoja industrijske simbioze v tej regiji

From industrial districts to industrial symbiosis: an opportunity. The case of Ponte Rosso area, Italy

The article highlights the importance of industrial symbiosis in the industrial ecology literature, which refers to geographically close relationships between companies in which networks and geographic proximity play a vital role. Industrial symbiosis traditionally deals with different industries in a collective approach to economic and environmental management. The research was carried out in the northeast of Italy in the autonomous region of Friuli Venezia Giulia, close to the Slovenian border. The Ponte Rosso was used as a case study. The empirical analysis served to highlight some critical aspects of the environmental, geographic-economic, and social factors that could hinder the development of industrial symbiosis in this region

Zapuščena naselja v gorskih območjih Furlanije - Julijske krajine: možnosti okrevanja Železne doline

The aim of this work is to demonstrate that new immigrations improve the appearance and socioeconomic situation of remote alpine regions. Friuli mountain villages, having become sparsely inhabited or indeed real ghost towns, are particularly suitable areas for such studies. The research builds on the one hand on analysis of the current state of the art as well as on analyses of official statistical data. It is on the other hand derived from own surveys in the course of investigative visits to all ghost towns in the research area. The results show that newcomers bring innovation and new impulses in agriculture, tourism, artistic and cultural sphere and play a key role in renovating existing buildings, reusing fallow plots of land and establishing a creative dynamic. Their activities increasingly enable the regeneration and maintenance of alpine cultural landscapes, resulting in new social and agrarian structures, which are emerging as »new farming« in the study area. The village of Dordolla in the Aupa Valley has recently established itself as a centre of innovation of these new processes and its achievements are evident in the rest of the valley, too. The regeneration processes analysed in the study area could also be transferred to other remaining partially abandoned settlements in Friuli-Venezia Giulia and broader

Monitoring pH-Triggered Drug Release from Radioluminescent Nanocapsules with X‑ray Excited Optical Luminescence

One of the greatest challenges in cancer therapy is to develop methods to deliver chemotherapy agents to tumor cells while reducing systemic toxicity to noncancerous cells. A promising approach to localizing drug release is to employ drug-loaded nanoparticles with coatings that release the drugs only in the presence of specific triggers found in the target cells such as pH, enzymes, or light. However, many parameters affect the nanoparticle distribution and drug release rate, and it is difficult to quantify drug release <i>in situ</i>. In this work, we show proof-of-principle for a “smart” radioluminescent nanocapsule with an X-ray excited optical luminescence (XEOL) spectrum that changes during release of the optically absorbing chemotherapy drug, doxorubicin. XEOL provides an almost background-free luminescent signal for measuring drug release from particles irradiated by a narrow X-ray beam. We study <i>in vitro</i> pH-triggered release rates of doxorubicin from nanocapsules coated with a pH-responsive polyelectrolyte multilayer using HPLC and XEOL spectroscopy. The doxorubicin was loaded to over 5% by weight and released from the capsule with a time constant <i>in vitro</i> of ∼36 days at pH 7.4 and 21 h at pH 5.0, respectively. The Gd₂O₂S:Eu nanocapsules are also paramagnetic at room temperature with similar magnetic susceptibility and similarly good MRI <i>T</i>₂ relaxivities to Gd₂O₃, but the sulfur increases the radioluminescence intensity and shifts the spectrum. Empty nanocapsules did not affect cell viability up to concentrations of at least 250 μg/mL. These empty nanocapsules accumulated in a mouse liver and spleen following tail vein injection and could be observed <i>in vivo</i> using XEOL. The particles are synthesized with a versatile template synthesis technique which allows for control of particle size and shape. The XEOL analysis technique opens the door to noninvasive quantification of drug release as a function of nanoparticle size, shape, surface chemistry, and tissue type