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Radiochromic film digitizers
Published in Indra J. Das, Radiochromic Film, 2017
Lasers are unique light sources because they produce spatially and temporally coherent light through the process of stimulated emission. A number of different types of lasers have been used for radiochromic film densitometry, but all lasers have particular defining characteristics such as incident laser power and wavelength. The optimum laser power is found by minimizing the probability of damaging the film and inducing unintended polymerization catalysis and maximizing the incident power to provide sufficient illumination of the sample (and, hence, lower measurement noise). Red lasers (635–670 nm) in the range of 1–10 mW are commonly employed for radiochromic film densitometry, as the GAFchromic™ (Ashland Advanced Materials, Bridgewater, NJ) line of radiochromic films exhibits maximum absorption in this range. The primary advantage of laser light is its spatial coherence, which allows for very small film regions of film to be illuminated. In this way, 2D film measurements are taken as the concatenation of many ideally independent point measurements, with minimal scatter or reflections from adjacent film areas. This is not the case for fluorescent light sources, in which the diffuse nature of the light causes significant positional dependence, especially at the furthest edges of the source. Laser light also generally provides the optimal measurement sensitivity, as a very narrow bandwidth tuned to the maximum film absorption peaks can be used. Figure 4.2 shows a representative spectral measurement of a 635-nm He–Ne laser. It should be mentioned that dosimetric accuracy can be compromised if the absolute position of the film absorption peak is susceptible to changes in absorbed dose, temperature, or other factors such as scattering, reflection, Newton’s ring artifacts, polarization, and so on. For very narrow light emission bandwidths, small shifts in the spectral absorbance of the film can cause large variations in measurements. In addition, as the polydiacetylene mechanism of GAFchromic radiochromic films involves planar polarization of polymeric crystals, measurements using coherent laser light suffer from significant polarization artifacts. Scanning densitometers utilizing laser light sources with computerized translation of various optical components are discussed in Section 4.3. Due to the relatively high cost and limited availability of such scanners, use of scanning laser densitometers is not common in clinical settings. However, a number of prototype scanning systems do employ narrow bandwidth measurement light to maximize the absolute film response. Such systems will be discussed in Section 4.3.
An update on liposomes in drug delivery: a patent review (2014-2018)
Published in Expert Opinion on Therapeutic Patents, 2019
Mazen M. El-Hammadi, José L. Arias
pH-responsive LPs can be used for site-selective drug release by exploiting the fact that some pathologies are associated with different pH values from that of normal tissues, as in tumor tissues which have often slightly more acidic than healthy tissues. Destabilization of the lipid bilayers is triggered by pH changes due to protonation/deprotonation of functional groups of the liposomal membrane leading to changes in permeability. DOPE is a representative example of natural PL that exhibit such a polymorphic phase behavior. While this PL adopts a bilayer structure (Lα phase) at neutral pH, a phase transition to inverted hexagonal phase II (HII phase) occurs at a low pH. A fluorogenic unilamellar LP comprising DOPE as well as N-palmitoyl homocysteine, and cross-linked polydiacetylene lipids has been formulated to provide an instant release of the encapsulated drug at acidic pH conditions [29]. While cross-linking of the diacetylene lipids inhibits leakage and retains stability, LPs undergo rapid fusion with each other when the pH is lowered from 7 to 4. This was evident by the increase of LP size by approximately 20-fold, from around 110 to 2000 nm, as the pH was lowered. This liposomal system also enables monitoring of drug release based on a non-fluorescent-to-fluorescent transition showed by polydiacetylene as a response to conformational changes such as that induced by LP-LP fusion [81]. It is anticipated that the drug release profile under specific pH conditions could be controlled by changing the molar ratio of the lipid constituents.
Peptides, proteins and nanotechnology: a promising synergy for breast cancer targeting and treatment
Published in Expert Opinion on Drug Delivery, 2020
Anabel Sorolla, Maria Alba Sorolla, Edina Wang, Valentín Ceña
NPs can serve as carriers of highly active peptides such as those able to disrupt the cellular membrane and initiate cytolysis or those able to internalize into the cells provided by their cell penetration properties. An example of membrane disruptive peptide is melittin. Melittin constitutes the ~50% of dry weight of honeybee venom and integrates into the phospholipids of the plasmatic membrane [76]. Melittin has shown antitumoral activity in multiple cancer models including BC [77,78,79,80]. However, due to its rapid lytic effects, its integration into NPs is preferred. The studies related to the delivery of melittin with NPs started with the utilization of hecate, a synthetic 23-amino acid amphipathic α-helical peptide analogue of melittin [81]. Hecate was incorporated in magnetic NPs and efficiently killed the BC cell line MDA-MB-435S in vitro [82]. Later, more disease-relevant studies pointed out the utility of melittin-loaded NPs to regress BC in vivo such as the work done by Soman et al in which they deployed perfluorocarbon NPs to decrease the growth of MDA-MB-435 xenografts with no apparent toxicity observed [83]. More sophisticated studies made use of melittin-derived NPs such as activatable protein NPs (APNPs) embedding melittin in their backbone together with the peptide PLGLAG, a well-known substrate of metalloproteinase-2 (MMP-2) and −9 (MMP-9) [84]. Treatment of MDA-MB-231 tumors in vivo with MMP-2 disassembled the intravenously administered melittin APNPs resulting in tumor growth reduction by 27% and apoptosis induction with limited toxicity [84]. A similar concept was investigated very recently by Zhou et al. Herein, the authors used the ability of natural MMP-2 to cleave an artificial gene (proMel), containing one copy of melittin and the peptide PLGLAG, which was delivered to BC brain metastases (MDA-MB-231) by polymeric NPs targeted with AMD3100 [85], which interacts with the CXCR4 [86]. The intravenous treatment with the engineered NPs reduced tumor progression and increased mice survival with limited systemic toxicity [85]. Another study utilizing melittin-derived NPs is the one using magnetic NPs functionalized with citric acid and anchoring electrostatically melittin and doxorubicin on the NPs’ surface. This nanoformulation resulted in a synergistic effect in cell death in MCF-7 cells [87]. Moreover, polyion complex micelles targeted with estrone induced cytotoxicity and enhanced cellular uptake in ER+ cells MCF-7 cells [88]. Other lesser exploited cytolytic peptides structurally very similar to melittin are cecropins and magainins. Magainin has been proposed for cancer therapy when delivered in polydiacetylene micelles for non-small cell lung cancer [89].