Effect of Oil Phase Lipophilicity on In Vitro Drug Release from O/W Microemulsions with Low Surfactant Content

ABSTRACT

In this work we investigated the effects of oil phase lipophilicity on in vitro drug release from topical o/w microemulsions (MEs) containing low percentages of emulsifiers. Three different lipids, isopropyl myristate (IPM), isopropyl palmitate (IPP), and isopropyl stearate (IPS), whose lipophilicity increased in the order IPM < IPP <IPS, were used as oil phase to prepare o/w MEs containing low amounts (7.7% w/w) of two surfactant/cosurfactant mixtures, isoceteth-20/glyceryl oleate (5:2) (MEs 1–3) and oleth-20/glyceryl oleate (5:2) (MEs 4–6). All the MEs were prepared using the phase inversion temperature (PIT) method.

Three active compounds (0.5% w/w), Naproxen (NAP), Idebenone (IDE), and Butylmethoxydibenzoylmethane (BMBM), were selected as model drugs and their release rates from PIT MEs were evaluated using Franz-type diffusion cells. All the MEs gave a mean droplet diameter ranging from 28 to 44 nm and showed a single peak in size distribution. The addition of IDE to MEs 1–6 did not significantly change ME droplet size. On the contrary, an increase of the droplet size beyond the ME limit (150 nm) was observed when isoceteth-20 was used as surfactant to prepare MEs containing NAP or MEs containing BMBM and IPS as oil phase. Pseudo-first order release rates were observed only for NAP from MEs 1–3, while MEs containing IDE showed an initial slow release followed by an increased release of the test compound. The release rate constants were found to be dependent on the ME composition and on the active compound incorporated. The highest release rate was observed from ME 1 containing IPM as oil phase and NAP as drug. As regards BMBM, its release rate was not calculated since no release was observed until 6 h from the beginning of the experiment. The cumulative amount of active compound released after 22 h was inversely related to drug lipophilicity (NAP Log P = 2,9; IDE Log P 3,5; BMBM Log P 4,8). These findings could be attributable to a reduced thermodynamic activity of the drugs in the vehicles containing the most lipophilic oil phase due to an increase of drug solubility which could lead to an unfavorable drug partition from the oil phase. The results of this study suggest that the choice of proper combinations of oil phase lipids and emulsifiers may allow achieving drug controlled delivery from topical o/w MEs with low emulsifier content.     

The inverse type II β-turn on D-Trp-Phe, a pharmacophoric motif for MOR agonists

Herein we propose the D ‐Trp‐Phe sequence within an inverse type II β‐turn as a new kind of pharmacophoric motif for μ‐opioid receptor (MOR) cyclopeptide agonists. Initially, we observed that c[Tyr‐D ‐Pro‐D ‐Trp‐Phe‐Gly] ( 4 ), an analogue of endomorphin‐1 (H‐Tyr‐Pro‐Trp‐Phe‐NH₂) lacking the crucial protonatable amino group of Tyr 1, is a MOR agonist with 10^?8 M affinity. Molecular docking analysis suggested that the relevant interactions with the receptor involve D ‐Trp‐Phe. The bioactive conformation of this region was investigated by selected derivatives of 4 designed to adopt an inverse type II β‐turn. These efforts led to c[Tyr‐Gly‐D ‐Trp‐Phe‐Gly] ( 14 ) and to the cyclotetrapeptide c[D ‐Asp‐1‐amide‐β‐Ala‐D ‐Trp‐Phe] ( 15 ), showing improved nanomolar affinity. Both 14 and 15 selectively bind MOR, as they have negligible affinity for the κ‐ and δ‐opioid receptors. Both 14 and 15 behave as partial MOR agonists in functional assays. Conformational and docking analyses confirm the role of the inverse β‐turn in binding. These results indicate that the D ‐Trp‐Phe inverse β‐turn structure can be used for designing non‐endomorphin‐like peptidomimetic opioid agonists in general, characterized by an atypical mechanism of interaction between ligand and receptor.     

Early development of a biodegradable energetic elastomer

The expected depletion of oil resources and a greater awareness for the environmental impact of plastic products have created a strong interest toward energetic polymers that are not only biodegradable but also obtainable from renewable resources. In this work, a copoly(ester/ether) was synthesized from polyepichlorohydrin and sebacoyl chloride using pyridine as a Lewis‐base catalyst. The chlorinated polymer was azidified with NaN₃ in dimethyl sulfoxide solutions. The success of the reaction was confirmed by ¹H‐NMR, ¹³C‐NMR, and Fourier‐transform infrared spectroscopy. Two types of polyurethane networks were synthesized from the nonenergetic and the energetic copolymers, adding polycaprolactone triol and using L ‐lysine diisocyanate as a nontoxic curing agent. The two resulting polyurethanes were soft thermoset elastomers. The polyurethanes were chemically and mechanically characterized, and their biodegradability was evaluated in compost at 55°C. The nonenergetic and the energetic polyurethanes showed a glass‐transition temperature of −14°C, and −23°C, respectively. The weight loss of the polyurethanes during the composting experiments was monitored. It increased almost linearly with time for both materials. After 20 days, the nonenergetic samples lost about 50% of their mass because of the biodegradation mechanism. Instead, the energetic elastomers lost only about 25% of their initial mass after 25 days. The experimental results revealed that the azide pendant group in the soft segment (the polyether segments) is the main factor that controls the physical, mechanical, and degradation properties of these polyurethane networks. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Advances in anodic alumina membranes thin film fuel cell: CsH2PO4 pore-filler as proton conductor at room temperature

Anodic alumina membranes (AAM) filled with cesium hydrogen phosphate proton conductor have been tested as inorganic composite electrolyte for hydrogen–oxygen thin film (≤50 μm) fuel cell (TFFC) working at low temperatures (25 °C), low humidity (T_gas = 25 °C) and low Pt loading (1 mg cm⁻²). Single module TFFC delivering a peak power of around 15–27 mW cm⁻², with open circuit voltage (OCV) of about 0.9 V and short circuit current density in the range 80–160 mA cm⁻² have been fabricated. At variance with pure solid acid electrolytes showing reproducibility problems due to the scarce mechanical resistance, the presence of porous alumina support allowed to replicate similar fuel cell performances over numerous AAM/CsH₂PO₄ assemblies. A scale-up process of the electrodic area has been optimized in order to increase the delivered peak power of AAM thin film fuel cell. Morphological, chemical and electrochemical studies on the alumina composite electrolyte have been carried out by means of scanning electron microscopy, X-ray diffractometry, Micro-Raman spectroscopy, DTA/DTG analysis, ac impedance spectroscopy and single fuel cell tests.     

On-line 2-satisfiability

We deal with the followingon-line 2-satisfiability problemP(m, n): starting fromC(0)=true, consider a sequence ofm Boolean formulasC(k) (inn variables and in conjunctive normal form), each of them being the intersection of the previous one with a single clause which is the union of two literals. Solve the sequence of 2-satisfiability problemsC(k)=true,k=1,...,m. It is well known that a 2-satisfiability problem involvingm clauses can be solved inO(m) time. Thus, by a naive approach one can solveP(m, n) in overallO(m ²) time. We present an algorithm with overallO(nm) time complexity, which for every formula not only checks its satisfiability, but also actually computes a solution (if any), and moreover, detects all forced and all identical variables. Our algorithm makes use of an efficient on-line transitive closure procedure by Italiano. We discuss two applications to the design of integrated electronic circuits and to edge classification in automated perception.To the memory of Bob Jeroslow     

Blue fish burgers: nutritional characterisation and sensory optimisation

In order to reduce waste of marine resources, valorise fishing discards and move towards fish consumption, a new ready-to-cook seafood product was developed. In particular, a chemical investigation on chub mackerel and hake was conducted to the aim of mixing the two fish species to produce nutritionally balanced fish burgers. In addition, to evaluate consumer opinion about these new fresh products and best acceptability of different proportions of mackerel and hake, focus group interviews and consumer test were also performed. The results of the chemical analyses achieved on both selected fish species gave rise to minimally processed fish products with a high amount of chub mackerel, therefore providing the desired nutritional properties and low level of hake in order to obtain firmer and wetter burgers. By means of focus group interviews, the novelty and high level of convenience of the developed fresh commodity was highlighted. Consumer test declared that the most successful sample was that with 70% chub mackerel and 30% hake.     

Investigations on the migration mode method (MMM) for reactor calculations

Current calculation codes for reactor analysis are based on the multi-group method to evaluate energy distribution of neutron flux. Usually a two energy group diffusion equation is adopted. This choice is adequate for PWRs associated to cross sections libraries tabulated versus fuel exposure and other state parameters as moderator density, fuel temperature, boron concentration. An improvement of this approach is represented by the migration mode method (MMM) by which the neutron spectrum is expanded in terms of base functions corresponding to the different modes of migration of the neutrons in the energy dimension. For a thermal reactor, three such functions may be easily identified: the Maxwellian distribution of the neutrons at thermal equilibrium with the moderator, the 1/E slowing down distribution (corrected to take into account resonance absorption effects) and the fission neutron spectrum. The (space-dependent) coefficients of the expansion are calculated by solving a differential equation which results having a structure similar to the one relevant to multi-group theory. The method can therefore be easily implemented adopting existing diffusion theory codes.     

Manufacturing personalized food for people uniqueness. An overview from traditional to emerging technologies

Abstract

Personalized nutrition means that we are unique in the way to absorb and to metabolize nutrients as a consequence of our genetic profile and the microbiome that we host in the gut. With the terminology of Personalized Food Manufacturing we want not only to stress the idea of the capability to manufacture food meeting our unique nutritional needs but – based on the idea that eating is a global experience – also to broad this to meet additional personal requirements and expectations, i.e. taste, texture, color, aspect, etc. To address this aim, traditional and advances technologies will have to be employed in new ways and new technological solutions will have to be implemented. All these considerations motivated our paper by which we want to explore and to discuss the technological options having the potential to produce personalized food. After pointing out the main diet styles, firstly we have analyzed the modern approaches of agricultural and animal nutrition in use to manufacture food for narrow group of consumers. Secondly, we have explored emerging technologies at disposal employable to manufacture customized food that meet our uniqueness. Finally the most important market products belonging in the sector of personalized food production have been considered.