Functionalized bacterial cellulose nanowhiskers as long‐lasting drug nanocarrier for antibiotics and anticancer drugs

Abstract

A nano drug carrier based on sustainable and biocompatible nanocellulose was developed for use in prolonged drug releases. The grafting of β-cyclodextrin (βCD) on bacterial cellulose nanowhiskers (BCNC) using citric acid (CA) as a green linker was performed. This led to the formation of functionalized BCNC-grafted-βCD (BCNC-g-βCD). Broad-spectrum antibiotic Ciprofloxacin (CIP) and anticancer drugs Doxorubicin (DOX) and Paclitaxel (PTX) were used as model drugs. These model drugs were conjugated to BCNC-g-βCD to form the drug-nanocarrier systems (BCNC-g-βCD-drug). The change in the nanowhiskers' surface chemistry, morphology, and crystallinity was characterized by FTIR, solid-state 13 C NMR, scanning electron microscopy (SEM), atomic force microscopy (AFM), and x-ray diffraction (XRD). The functionalized nanowhiskers showed a significant increase in the drug payloads, which ranged from 495 ±4-810 ±7 μg/mg, along with a radical improvement in the drug release profiles. For all of the developed drug-conjugated nanocarriers, the initial burst releases were reduced effectively. The observed drug releases showed a sustained and controlled manner, with cumulative releases of 75-90 % over 5-5.5 days. Nevertheless, an improved drug release performance was observed in the acidic pH of 6.4 that mimicked extracellular tumor cells. In vitro drug release data were fitted zero-order kinetic model with drug release constants (K 0 ) of 0.68, 0.74, and 0.79 μg drug/h (at pH 6.4 and 37°C) for BCNC-g-βCD-CIP, BCNC-g-βCD-DOX, and BCNC-g-βCD-PTX nanosystems, respectively. The observed higher payloads along with the slow releases of drugs from the developed nanocarrier suggests its promising potential for reducing the frequent daily dosing and minimizing systemic toxicity of loaded drugs.

Cytotoxicity of metformin against HT29 colon cancer cells contributes to mitochondrial Sirt3 upregulation

“…Some antidiabetic drugs were evaluated as anticancer and cytotoxic agents, which showed positive results. [ 26,27 ] Although metformin is a first‐line drug for type 2 diabetes, due to its mitochondrial effects, it is also under investigation as an anticancer agent. Our previous studies have indicated that some herbal medicines used traditionally for both cancer and diabetes, including Capparis spinose, Teucrium polium , and Prosopis farcta , induced a significant cytotoxicity in HT‐29 cells and regulated the mitochondrial function (i.e., mitochondrial membrane potential collapse and ROS overproduction) and cell death.…”

Application or function of citric acid in drug delivery platforms

“…For all of the drug‐loaded nanocarriers, the observed slow drug release results were fitted with a zero‐order kinetic model. The output of this study approved the potential of this method for preparation of the efficient systems with reducing frequent daily dosing 197 …”

“…The output of this study approved the potential of this method for preparation of the efficient systems with reducing frequent daily dosing. 197 Guan et al designed the CA-modified poly(lactic acid)-poly(L-lysine) (PLA-PLL)/FA to evaluate its performance as DDS for drug delivery. In the system, micellar poly(lactic acid) (PLA) was employed as the hydrophobic portion, and poly(L-lysine) (PLL) was used as the hydrophilic portion.…”

Issue Highlights

“…Moreover, promoted drug release profiles were pragmatic in an acidic pH of 6.4 at 37°C, which mimics the tumour environment. The obtained observations demonstrate versatile medical applications for the obtained nanocarriers in localized and long‐lasting drug delivery …”