<p>Fabricating β-cyclodextrin based pH-responsive nanotheranostics as a programmable polymeric nanocapsule for simultaneous diagnosis and therapy</p>

Abstract

Background Fabrication of a smart drug delivery system that could dramatically increase the efficiency of chemotherapeutic drugs and reduce the side effects is still a challenge for pharmaceutical researchers. By the emergence of nanotechnology, a huge window was opened towards this goal, and a wide type of nanocarriers were introduced for delivering the chemotherapeutic to the cancer cells, among them are cyclodextrins with the ability to host different types of hydrophobic bioactive molecules through inclusion complexation process. Aim The aim of this study is to design and fabricate a pH-responsive theranostic nanocapsule based on cyclodextrin supramolecular nano-structure. Materials and methods This nanostructure contains iron oxide nanoparticles in the core surrounded with three polymeric layers including polymeric β-cyclodextrin, polyacrylic acid conjugated to sulfadiazine, and polyethylenimine functionalized with β-cyclodextrin. Sulfadiazine is a pH-responsive hydrophobic component capable of making inclusion complex with β-cyclodextrin available in the first and third layers. Doxorubicin, as an anti-cancer drug model, was chosen and the drug loading and release pattern were determined at normal and acidic pH. Moreover, the biocompatibility of the nanocapsule (with/without drug component) was examined using different techniques such as MTT assay, complement activation, coagulation assay, and hemolysis. Results The results revealed the successful preparation of a spherical nanocapsule with mean size 43±1.5 nm and negatively charge of −43 mV that show 160% loading efficacy. Moreover, the nanocapsule has an on/off switching release pattern in response to pH that leads to drug released in low acidic pH. The results of the biocompatibility tests indicated that this nano drug delivery system had no effect on blood and immune components while it could affect cancer cells even at very low concentrations (0.3 μg mL −1 ). Conclusion The obtained results suggest that this is a “switchable” theranostic nanocapsule with potential application as an ideal delivery system for simultaneous cancer diagnosis and therapy.

Naringenin Nano-Delivery Systems and Their Therapeutic Applications

“…They also allow controlled release and targeting to specific organs or tissues, improving their performance via increasing their bioavailability and reducing their undesirable side effects. The nanosize of these components and their engineered surface helps them pass through the vessels to reach a specific organ [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. Thus, nanocarriers have been extensively used for the encapsulation of different phytochemicals, including NRG or naringin which is its glycosidic form [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ].…”

Stimuli-responsive cyclodextrin-based supramolecular assemblies as drug carriers

“…47 In addition to pH-responsive units or polymer chains, pH-responsive guest molecules such as benzimidazole (BM) and sulfadiazine are employed. 48,49 The protonation and deprotonation of BM can regulate the formation of inclusion complexes. At physiological pH of 7.4, the hydrophobic nature of BM benefits the formation of the BMCD inclusion complex.…”

Cyclodextrin Modified Block Polymer for Oral Chemotherapy

“…Although, intravenous path of cancer treatment is more popular than other methods, oral medication is considered to be a cornerstone in potential treatment [4]. The oral path permits pain free self-medication through the patient's point of view and therefore is the crucial practical path.…”

“…Iron oxide (Fe 2 O 3 ) was synthesized by a known co-precipitation method, wherein FeCl 2 .4H 2 O and FeCl 3 .6H 2 O were dissolved in 0.5 M of degassed HCl followed by frequent addition in 300 ml of 0.5 M ammonia solution to obtain a reaction solution and was mechanical stirred in nitrogen environment for 25 minutes at 50 degree celsius with 9.5 pH to obtain nanoparticles [4]. The nanoparticles were further collected and washed with deionized water and ethanol followed by freeze drying.…”

“…All the prepared samples can be identified as having a pH-responsive activity in the release sequence. In addition, release approach describes a continuous release pattern to allow for release rate also after 2 weeks [4].…”