PEGylated and poloxamer-modified chitosan nanoparticles incorporating a lysine-based surfactant for pH-triggered doxorubicin release

Abstract

28The growing demand for efficient chemotherapy in many cancers requires novel approaches in 29 target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have 30 potential ability to selectively release the encapsulated molecules by sensing the acidic tumor 31 microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)-32 and poloxamer-modified nanocarriers have been gaining attention regarding their potential to 33 improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive 34 nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these 35 modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and 36 tripolyphosphate were selected to form NPs by the interaction of oppositely charged 37 compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. 38The strong dependence of 77KS ionization with pH makes this compound an interesting 39 candidate to be used for the design of pH-sensitive devices. The physicochemical 40 characterization of all NPs has been performed, and it was shown that the presence of 77KS 41 clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of 42 DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG 43 or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs 44 improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown 45 the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest 46 that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and 47 intracellular environments, rendering them promising DOX carrier systems for cancer therapy. 48 Keywords: chitosan nanoparticles; doxorubicin; in vitro release; in vitro cytotoxicity; lysine-49 based surfactant; pH-sensitivity 50

Increased ROS Scavenging and Antioxidant Efficiency of Chlorogenic Acid Compound Delivered via a Chitosan Nanoparticulate System for Efficient In Vitro Visualization and Accumulation in Human Renal Adenocarcinoma Cells

“…In in vitro studies, cultured cells propagated in media are exposed to high levels of lactic acid, which may decrease the intracellular pH environments. This lower pH condition protonates more amine groups of CNP° causing its encapsulated contents to be dissociated and released intracellularly [103,104,105]. Hypothetically, in in vivo condition the degradation of the vector likely be aided by the lysozyme activity or swell under the influence of endosome or lysosome pH [106,107,108,109].…”

Leakage-free DOX/PEGylated chitosan micelles fabricated via facile one-step assembly for tumor intracellular pH-triggered release

“…Recently, chitosan and its derivatives in the forms of nanoparticles and micelles have been widely investigated for tumor chemotherapy and diagnosis due to their unique characteristics, such as biocompatibility, biodegradability, remarkable cell membrane penetrability, pH-dependent therapeutic unloading, ease to multi-functionalization, and so on [21], especially the PEGylated chitosan copolymers [22]. And for most of the chitosan and its derivatives-based nanoparticles and micelles, the drug carriers were fabricated at first, and then the drugs were loaded [23][24][25][26]. Because of it nature of polycation, the targeted pH-mediated intracellular release of methotrexate disodium (MTX) has been reported with the crosslinked chitosan microgels as vehicle, benefiting from the swelling of chitosan in different media [27].…”

A Micelle Self-Assembled from Doxorubicin-Arabinoxylan Conjugates with pH-Cleavable Bond for Synergistic Antitumor Therapy

“…The AX-DOX micelles are stability in neutral solution, limiting the release of DOX. However, the micelles can dissolve into the acidic media, which promotes hydrogen bonds cleavage [ 23 ], therefore the micelles are disintegrated and promote the release of DOX.

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“…After incubation for 1 h, the absorption of the samples in each well was measured using a BIO-TEK ELx800 Universal Microplate Reader (Bio-Tek, VT, USA) at wavelengths of 450 and 630 nm. The cell survival rate was calculated with the following formula: [( A E − A B )/( A C − A B )] × 100%, where A E , A C , and A B represent the absorbance of the experimental cells [ 23 ], control cells, and background, respectively.…”