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Pharmaceutical and Methodological Aspects of Microparticles
Published in Neville Willmott, John Daly, Microspheres and Regional Cancer Therapy, 2020
Yan Chen, Mark A. Burton, Bruce N. Gray
For biodegradable microparticles prepared from polyesters, degradation can be affected by the hydrophobicity and the crystallinity of the polymer98,110 and the presence of plasma proteins.111 Thus, a high degree of hydrophobicity or crystallinity can slow the process of hydration and water penetration, resulting in slow degradation. Copolymerization destroys a polymer’s crystallinity, which may produce more readily degradable matrices.110 In a systematic study of the relationship between proportion of polylactate/polyglycolate and degradation rate, it was found that the copolymer of lactic acid and glycolic acid (1:1) showed the maximal biodegradation rate in vivo.112 With regard to the presence of plasma proteins, their adsorption on the surface of poly(l-lactide) microcapsules causes an increase in H+ concentration at the surface as well as increases the solubility of the polymer. In turn, these accelerate the degradation of poly(l-lactide) microcapsules.111
Advances in stent technology
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
Smriti Saraf, Paul Bhamra-Ariza
The Ultimaster Stent is a thin-strut, CoCr, biodegradable-polymer, sirolimus-eluting coronary stent. It has an open cell two-link design with a stent strut thickness of 80 micron resulting in greater flexibility without compromising radial force. The polymer DL-lactide-co-caprolactone degrades over a period of 3–4 months and the drug is coated on the abluminal side preventing delamination. In the Century II multicentre trial, Ultimaster was compared to the Xience stent in 194 patients and no significant difference was noted in clinical outcomes at 1 year between the two arms.73
Scaffold processing
Published in Yoshinobu Onuma, Patrick W.J.C. Serruys, Bioresorbable Scaffolds, 2017
John J. Scanlon, Joseph M. Deitzel, Dieter Mairhörmann, Roland Wölzein
Poly(L-lactide) is a thermoplastic homopolymer produced by polymerization of a monomer comprised of L-lactide. Polymerization is the process of converting the L-lactide monomer molecules into a polymer. A polymer is a large molecule, or macromolecule, comprised of many repeating interconnected monomer subunits. Lactide is derived from lactic acid (2-hydroxypropanoic acid), which is formed by bacterial fermentation of dextrose. Poly(L-lactide) is produced by ring-opening polymerization using hydroxyls as initiators. The polymerized poly(L-lactide) is typically produced in the form of pellets that are converted into other shapes by extrusion, molding, or spinning processes.
Icaritin-loaded PLGA nanoparticles activate immunogenic cell death and facilitate tumor recruitment in mice with gastric cancer
Published in Drug Delivery, 2022
Yao Xiao, Wenxia Yao, Mingzhen Lin, Wei Huang, Ben Li, Bin Peng, Qinhai Ma, Xinke Zhou, Min Liang
PLGA polymers were synthesized as previously reported (Tabatabaei et al., 2016). PLGA-PEG copolymers (PEG2000) were prepared by melt polymerization under vacuum using stannous octoate [stannous 2-ethylhexanoate] as a catalyst. DL-Lactide (1.441 g), glycolide (0.285 g), and PEG2000 (0.77 g) (45%/w) were heated to 140 °C in a bottleneck flask under a nitrogen atmosphere for complete melting. The molar ratio of DL-lactide to glycolide was 3:1. Stannous octoate [0.05% (w/w)] was added, and the temperature of the reaction mixture was increased to 180 °C. This temperature was maintained for 4 h. Polymerization was performed under vacuum. The copolymer was recovered by dissolution in methylene chloride, followed by precipitation in ice-cold diethyl ether. After 24 h, PLGA-PEG was purified by washing with ethanol and drying under vacuum. Icaritin (0.5 mg) was dissolved in 500 μL dimethyl sulfoxide and mixed with 5 mg of PLGA-PEG in the drug solution. The drug-polymer mixture was added dropwise to 10 mL of deionized water while stirring and stirred for 24 h at room temperature in a beaker. PLGA@Icaritin was obtained, dialyzed to remove the organic solvent, and freeze-dried.
An overview of PLGA in-situ forming implants based on solvent exchange technique: effect of formulation components and characterization
Published in Pharmaceutical Development and Technology, 2021
Tarek Metwally Ibrahim, Nagia Ahmed El-Megrab, Hanan Mohammed El-Nahas
The choice of PLGA grade may be considered as the key factor in the process of modifying the drug release from PLGA-ISFI systems. Where, the polymer degradation, phase inversion dynamics and polymeric matrix erosion are strongly influenced by proper selection of PLGA type and grade (Ahmed et al. 2014; Woodard and Grunlan 2018). The composition of PLGA is a critical point for controlling drug delivery through ISFI systems. The proportion and distribution of both lactide and glycolide inside the PLGA chains are fundamental parameters to modulate the system’s hydrophobicity and crystallinity and to influence the solvent-water exchange rate and degradation (Jerbić 2018). Glycolide has a slightly higher hydrophilic nature than lactide. This can represent more labile glycolide-lactide bonds into the polymeric backbone. Where, the increment of the content of glycolide can promote the rate of hydrolysis. Kamaly et al. (2016) reported that the decrement of the number of lactic acid monomers and increment of glycolic acid monomers would promote the water uptake into the ISFI system. This could be ascribed to the high exposure of ester bonds to hydrolysis and the low content of methyl groups on the lactic acid moieties. Hence, an accelerated degradation rate could be exhibited.
Triggering receptor expressed on myeloid cells-1 (TREM-1) as a therapeutic target in infectious and noninfectious disease: a critical review
Published in International Reviews of Immunology, 2020
Pedro Henrique dos Santos Dantas, Amanda de Oliveira Matos, Ernandes da Silva Filho, Marcelle Silva-Sales, Helioswilton Sales-Campos
These results suggest LR12 as a prominent molecule in the treatment of inflammatory diseases in which TREM-1 plays a pivotal role. Interestingly, pharmacokinetics and different formulations of LR12 have been tested in vivo [102]. LR12 was administered in rats by in situ implants of poly-lactide-co-glycolide and poly-lactide (that provided sustained release of the peptide) for seven days, and presented good bioavailability [102]. This peptide is now commercially known as Nangibotide®, and was tested through continuous intravenous administration in humans, showing to be safe and well tolerated even at high doses (6 milligrams/kg, uninterruptedly during 7 h and 45 minutes) [103]. Furthermore, patients treated with Nangibotide® displayed few adverse events, and did not develop any side effects 28 days after its administration [103]. Hence, LR12 may be safely used in humans due to good pharmacokinetic parameters, tolerability and stability.