Polymeric nanocapsules embedded with ultra-small silver nanoclusters for synergistic pharmacology and improved oral delivery of Docetaxel

Abstract

Despite of the remarkable cytotoxic and imaging potential of ultra-small metal nanoclusters, their toxicity-free and targeted delivery to cancerous cells remains a substantial challenge that hinders their clinical applications. In this study, a polymeric scaffold was first synthesized by grafting folic acid and thiol groups to chitosan (CS) for cancer cell targeting and improved gastric permeation. Furthermore, silver nanocluster (Ag NCs) were synthesized in situ, within CS scaffold by microwave irradiation and core-shell nanocapsules (NCPs) were prepared with hydrophobic docetaxel (DTX) in the core and Ag NCs embedded CS in the shell. A significant cytotoxicity synergism (~300 folds) was observed for DTX with co-delivery of Ag NCs against breast cancer MDA-MB-231 cells. Following oral administration, the DTX-Ag-NCPs increased bioavailability due to enhanced drug transport across gut (9 times), circulation half-life (~6.8 times) and mean residence time (~6.7 times), as compared to the control DTX suspension. Moreover, 14 days acute oral toxicity of the DTX-Ag-NCPs was performed in mice and evaluated for changes in blood biochemistry parameters, organ to body weight index and histopathology of liver and kidney tissues that revealed no significant evidence of toxicity suggesting the safety and efficiency of the DTX-Ag-NCPs as hybrid nanocarrier for biocompatible delivery of metal nanoclusters.

Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Improved Oral Bioavailability of Chlorpromazine: In Vitro and In Vivo Evaluation

“…PK Solver (a free Microsoft Excel Add-in) was used to calculate the area under the curve from concentration versus time curve to last measured time (AUC 0–24 ) and other pharmacokinetic parameters. Absolute bioavailability was calculated from absolute dose and areas under curves (AUC) for oral against intravenous administration [20].…”

Chitosan-Based Nanomaterials for Drug Delivery

“…Based on the physiochemical characters of CS, proven approaches such as ionic gelation, covalently crosslinked, and self-assembly have been developed to fabricate different forms of nanomaterials. Furthermore, the combination of CS with special inorganic nanoparticles (mesoporous silica and magnetic and gold nanoparticles) has also been used for well-controlled drug delivery [ 20 ]. In addition, the nanomaterials of different sizes and morphology have been generated using methods earlier described.…”

“…Oral administration (OD) is the preferred dosage form for the development of new drugs because of its convenience, safety, and patient tolerance [ 3 ]. Drugs are absorbed into the blood circulation through the gastrointestinal epithelial cells after reaching the gastrointestinal tract, then their therapeutic effects are imparted to tissue and organs [ 20 , 133 ]. However, the OD method of drug administration is generally slow, and some drugs may be damaged by gastric acid or irritate the gastrointestinal tract [ 134 ].…”

“…Nanoparticle geometry could significantly affect the rate of drug loading and drug transport, and the balance between the size and geometry is critical to the efficiency of drug delivery. In addition, drugs wrapped by nanomaterials prolong their circulation time, thereby improving their biodistribution and pharmacodynamics [ 4 , 20 ]. Lastly, nanomaterials modified by other bioactive molecules would exhibit distinct functions, including specific targeting or the characteristics of environmental responsiveness, thereby facilitating in drug accumulation and better reaching its effective dose [ 21 , 22 ].…”

Evaluation of Turmeric Nanoparticles as Anti-Gout Agent: Modernization of a Traditional Drug

“…The samples were analyzed at 20 kV, focusing at 500 nm scale. Moreover, energy-dispersive X-ray (EDX) was performed to quantify the elements in T-NPs [27].…”