Alzheimer’s disease is a neurodegenerative disorder that is caused by the accumulation of beta‐amyloid plaques in the brain. Currently, there is no definitive cure available to treat Alzheimer’s disease. The available medication in the market has the ability to only slow down its progression. However, nanotechnology has shown its superiority that can be applied for medical usage and it has a great potential in the therapy of Alzheimer’s disease, specifically in the disease diagnosis and providing an alternative approach to treat Alzheimer’s disease. This is done by increasing the efficiency of drug delivery by penetrating and overcoming the blood‐brain barrier. Having said that, there are limitations that need to be further investigated and researched in order to minimize the adverse effects and potential toxicity and to improve drug bioavailability. The recent advances in the treatment of Alzheimer’s disease using nanotechnology include the regeneration of stem cells, nanomedicine, and neuroprotection. In this review, we will discuss the advancement of nanotechnology which helps in the diagnosis and treatment of neurodegenerative disorders such as Alzheimer’s disease as well as its challenges.
Curcumin (CUR), a curcuminoid originating from turmeric root, possesses diverse pharmacological applications, including potent anticancer properties. However, the use of this efficacious agent in cancer therapy has been limited due to low water solubility and poor bioavailability. To overcome these problems, a drug delivery system was established as an excipient allowing improved dispersion in aqueous media coupled with enhanced in vitro anticancer effects. Different analyses such as UV–vis spectroscopy, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), solubility and dissolution assays were determined to monitor the successful encapsulation of CUR within the inner cavity of a β-cyclodextrin (β-CD) complex. The results indicated that water solubility was improved by 205.75-fold compared to pure CUR. Based on cytotoxicity data obtained from MTT assays, the inclusion complex exhibited a greater decrease in cancer cell viability compared to pure CUR. Moreover, cancer cell migration rates were decreased by 75.5% and 38.92%, invasion rates were decreased by 37.7% and 35.7%, while apoptosis rates were increased by 26.3% and 14.2%, and both caused caspase 3 activation toward colorectal cancer cells (SW480 and HCT116 cells). This efficacious formulation that enables improved aqueous dispersion is potentially useful and can be extended for various chemotherapeutic applications. Preliminary toxicity evaluation also indicated that its composition can be safely used in humans for cancer therapy.
Curcuminoids originating from turmeric roots are renowned for their diverse pharmacological applications, particularly as a natural anticancer agent. Unfortunately, harnessing the full potential of curcumin derivatives in cancer therapy has been impeded by its inherent limitations, specifically instabilities owing to poor solubility, leading to low systemic bioavailability under normal physiological circumstances. To circumvent this, a novel organic-based drug delivery system employing physically adsorbed β-cyclodextrin (βCD) as an excipient was developed in this study. This resulted in improved aqueous dispersion coupled with anticancer enhancements of tetrahydrocurcumin (THC) at a molar ratio of 2:1. Encapsulation of this agent was confirmed by physicochemical characterisation using UV–vis spectroscopy, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and both in vitro and in vivo approaches. Through the presence of an inclusion complex, a higher aqueous dispersion (65-fold) resulting in a higher drug content and an elevated release profile was achieved. Athymic nude (Nu/Nu) mice exposed to this treatment displayed improvements in tumour regression compared to stand-alone agents, consistent with in vitro cytotoxicity assays with an SI value > 10. The inclusion complex further enhanced apoptosis, as well as anti-migration and anti-invasion rates. Mechanistically, this formulation was consistent in terms of caspase 3 activation. Furthermore, the inclusion complex exhibited reduced systemic toxicity, including reduced inflammation in vital organs as examined by hematoxylin and eosin (H&E) staining. This study also revealed a notable sequential reduction in serum levels of tumour markers, including carcinoembryonic antigen (CEA) and mouse Cytochrome P450 1A2 (CYP1A2), correlating with a significant decrease in tumour bulk volume upon treatment commencement. These compelling findings highlight the potential of this formulation to empower insoluble or poorly soluble hydrophobic agents, thus offering promising prospects for their effective utilisation in colorectal cancer (CRC) chemotherapy.
27 June 2022 in Asia-Pacific Journal of Molecular Biology and Biotechnology
One of the drivers for early carcinogenesis involves specific somatic point substitution mutations in the KRAS gene which damages its ability to conduct signal transduction. Although antibodies can be used for the targeting of KRAS antigen, their localization along the cell’s inner membrane serves as a barrier against the accessibility of the antibodies. This study describes the evaluation of two internalization strategies, namely the endocytosis-based cell penetrating peptide (CPP) approach and the adenoviral-based intrabody (IB) approach, for the delivery of an anti-mutant KRAS single-chain variable fragment (scFv) into the cell. Splicing by overhang extension polymerase chain reaction (SOE-PCR) was used for the fusion of scFv with an enhanced green fluorescence protein (eGFP) and Antennapedia-PTD (Antp), a cell penetrating signal peptide. The fused construct (Antp-scFv-eGFP) at a concentration of 0.085 mg/ml was expressed in E. coli (BL21), while recombinant adenoviral particles containing the scFv-eGFP gene were harvested from HEK 293 cells. Both SW480 and HeLa cells were treated with Antp-scFv-eGFP and recombinant adenoviral particles, and their eGFP localization and intensity were compared to determine their scFv binding efficiencies. The IB approach was shown to exhibit a 3-fold higher fluorescence signal intensity compared to the CPP approach. This proof-of-concept study demonstrated that both antigens for either screening, diagnostic approaches can be potentially adopted when targeting various intracellular or therapeutic purposes.