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Lysosomes

Lysosomes are considered to be final organelles in endocytic as well as autophagocytic pathways. These vesicles are the final destination for numerous components [38]. Lysosomes can influence biochemical events such as expression of surface receptors and inhibition of microbial infections [39,40]. Microscopic examinations demonstrate that the structure and volume of lysosomes are nonuniform. The internal environment of lysosomes is acidic in nature with a pH of 4.6—5 [41]. This acidity is created and maintained by numerous H+ ATPases. The lysosomal membrane is degraded following treatment of cells with pH-sensitive chitosan nanoparticles encapsulating methotrexate (MTX). Fig. 8.5 depicts the effect of MTX-loaded nanoparticle on lysosomal membrane. This process has been investigated with acridine orange (AO) relocation technique [42]. While designing nanoformulations, investigators need to be careful that the target of the drug delivery system is not the lysosome. These particles need to undergo endosomal escape before formation of lysosome. Once the nanostructures are engulfed by lysosome the particles are degraded and are unable to deliver their payload ifthe target is nucleus, mitochondria, or some other organelle.

Assessment of the effects of chitosan nanoparticles

Figure 8.5 Assessment of the effects of chitosan nanoparticles (NPs) encapsulating methotrexate (MTX) (MTX-CS-NPs) on lysosomal membrane permeabilization in HeLa cells as visualized via AO staining. In untreated control cells, lysosomes can be seen as red—orange granules and cytoplasm shows a diffuse green fluorescence. In cells with lysosomal membrane damage (HeLa cells treated with 50 mg/mL MTX-CS-NPs) is evident [42].

 
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