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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
The effect of the chemical nature of the drug on the release characteristics of microspheres was demonstrated by Goedemoed et al.50 They reported that poly-phosphazene microspheres containing melphalan methyl ester showed sustained release, whereas the melphalan-loaded microspheres prepared from the same polymer exhibited high initial release that was not sustained. For a given matrix material, this illustrates the significant role the chemical properties of a drug play.
Injectable Scaffolds for Bone Tissue Repair and Augmentation
Published in Naznin Sultana, Sanchita Bandyopadhyay-Ghosh, Chin Fhong Soon, Tissue Engineering Strategies for Organ Regeneration, 2020
Subrata Bandhu Ghosh, Kapender Phogat, Sanchita Bandyopadhyay-Ghosh
Several synthetic (man-made) polymer based composite materials have also shown promise as injectable materials. Injectable formulations are often prepared from highly hydrated synthetic polymers which self-regulate to form hydrogels by physical or chemical cross-linking mechanisms (Hasnain et al. 2019). Synthetic polymers that have been employed as injectable carriers for tissue-engineering applications comprise of a variety of hydrophilic/hydrophobic copolymer combinations of poly (lactic acid) (PLA), poly (lactic-co-glycolic) acid (PLGA), poly (ethylene glycol) (PEG), poly (glycolic acid) (PGA), poly (vinyl alcohol) (PVA), poly (glutamic acid) (PGA) poly (N-isopropylacrylamide) (PNIPAM), poly (phosphazenes) (PPZ) etc. and copolymers of poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO), under the commercial names of Pluronics and Polyoxamer (Migliaresi et al. 2007, Tan and Marra 2010, Tian et al. 2012, Rojo et al. 2014). Polypropylene fumarate, poly (hydroxyethyl methacrylate) (PHEMA) have also been used as an injectable polymer to fill bone defects, particularly in cancellous bone. The material can be injected at the targeted site, degrade with respect to time and are cross-linkable in situ. In another example, porous PLGA/Ca-P cement composites have exhibited osteoinductive properties and bone-like mineralization, when used assubcutaneous implants (Migliaresi et al. 2007, Ruhé et al. 2006).
Otitis Media with Effusion
Published in John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed, Paediatrics, The Ear, Skull Base, 2018
In the future, both biofilm formation with infective complications and persistent perforation may be reduced or abolished by a currently experimental biodegradable, absorbable ventilation tube manufactured from poly-bis (ethylanate) phosphazene.151
Polymeric nanostructure vaccines: applications and challenges
Published in Expert Opinion on Drug Delivery, 2020
Rosana Simón-Vázquez, Mercedes Peleteiro, África González-Fernández
Polyphosphazenes (PPZs), with a nitrogen-phosphorous backbone and grafted organic side groups, are another example of polymers that might have self-adjuvant properties, such as the case of poly[di(carboxylatophenoxy)phosphazene] (PCPP) or poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP). PCPP induces a predominantly T helper 2 (Th2) immune response, mediated by interleukin 4 (IL-4) release, while PCEP induces a balanced Th1/Th2 immune response, associated with the production of both interferon gamma (IFNγ) and IL-4 [80]. These polymers can form a complex with the Ag or be used to synthesize other nanostructures, such as NPs or hydrogels [81].
Regioselective approach to colchiceine tropolone ring functionalization at C(9) and C(10) yielding new anticancer hybrid derivatives containing heterocyclic structural motifs
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Krystian Pyta, Natalia Skrzypczak, Piotr Ruszkowski, Franz Bartl, Piotr Przybylski
In order to functionalise 2 towards linkers for the construction of hybrids, we performed SN2-type etherifications of the tropolone hydroxyl group (Figure 2, Tables 1 and 1S; Supplemental Material). Regarding the tautomerization process of 2, the influence of base type, solvent, and substituent structure on the reaction course with the competitive formation of the two 3- or 4-type products (Figure 2) was tested. We focussed first on benzyl bromide as a reactant (Table 1). The most favourable conditions for the formation of the 3-type products were found using the inorganic bases NaH or K2CO3. Under those conditions the privileged formation of C(9)-ether derivative occurred (∼70%). The presence of THF as a solvent contributes to the highest ratio of C(9)/C(10) products (Table 1). The change of the inorganic base into the organic one (MTBD) in THF evokes the lack of regioselectivity because a nearly equimolar mixture of 3 with 4 was formed. A similar result was obtained when acetonitrile, acetone, and DMF were used as solvents. Favourable formation of C(10) products [ratio C(9)/C(10) was 30/70] took place when MTBD was dissolved in aromatic-type solvents (xylene or toluene). The use of other organic bases such as TMG, phosphazene-base P1-H, TMGN, or TBD yielded predominantly the 4-type product. The phosphazene base allowed to obtain a similar C(9)/C(10) ratio, as for MTBD, whereas the best regioselectivity towards the formation of the 4-type product (75%) was achieved with TMG. Thus, as indicated above, the use of the inorganic base/THF system is beneficial for the formation of C(9) analogues (of 3-type), whereas application of the organic base/toluene system alters the regioselectivity towards the favourable formation of C(10) analogues (of 4-type). In the next step, the influence of the alkyl bromide structure on the etherification site within 2 was studied (Table 1). With the NaH/THF-DMF system the highest regioselectivity was observed for cinnamyl bromide (up to 77% 3c, Table 1S; Supplemental Material). In turn, the use of propargyl bromide and ethyl bromoacetate limited the regioselectivity of the reaction. The use of the MTBD/toluene system with propargyl bromide and ethyl bromoacetate was quite beneficial (>70% of 4f, 4g) whereas the use of cinnamyl and 4-iodobenzyl bromides led to a less favourable formation of 4-type product (Table S1).