Abstract
The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are attractive nanocarriers due to their biodegradable, biocompatible, and relative malleable porous frameworks that can be functionalized for enhanced targeting and delivery in a variety of disease models. The optimal formulation of an MSN with polyethylene glycol (2% and 5%) and chitosan was undertaken, to produce sterically stabilized, hydrophilic MSNs, capable of efficient loading and delivery of the hydrophobic anti-neoplastic drug, doxorubicin (DOX). The pH-sensitive release kinetics of DOX, together with the anticancer, apoptosis and cell-cycle activities of DOX-loaded MSNs in selected cancer cell lines were evaluated. MSNs of 36–60 nm in size, with a pore diameter of 9.8 nm, and a cumulative surface area of 710.36 m2/g were produced. The 2% pegylated MSN formulation (PCMSN) had the highest DOX loading capacity (0.98 mgdox/mgmsn), and a sustained release profile over 72 h. Pegylated-drug nanoconjugates were effective at a concentration range between 20–50 μg/mL, inducing apoptosis in cancer cells, and affirming their potential as effective drug delivery vehicles.
Highlights
Nanotherapeutics postulates the use of nanotechnology for the alleviation of a variety of diseases, by diversifying treatment options and reducing conventional treatment- associated side effects [1]
Tetraethyl orthosilicate (TEOS, Si(OCH2CH3)4), Triton X-100 (TX100), cetyltrimethyl-ammonium bromide (CTAB, 99%), polyethyleneglycol2000 (PEG2000 ), chitosan (75–85 % deacetylated), sodium tripolyphosphate (TPP), Tween 20, ammonia solution (28–30%), sulphuric acid, sodium carbonate (Na2 CO3 ), doxorubicin hydrochloride (DOX, Mw: 579.98 g mol−1 ), and deuterium oxide, were all purchased from Sigma Aldrich (St Louis, MO, USA)
A hydrophilic mesoporous matrix was designed for the optimal loading capacity of the hydrophobic drug, DOX. These Mesoporous silica nanoparticles (MSNs) showed optimal DOX loading and were able to release the drug with moderate efficacy, with no erosion or friction affecting the release behaviour
Summary
Nanotherapeutics postulates the use of nanotechnology for the alleviation of a variety of diseases, by diversifying treatment options and reducing conventional treatment- associated side effects [1] This has inspired the design of various nanocarriers that aim to reduce pure drug concentrations and dosing frequencies, commonly associated with the onset of toxicities and drug resistance, by providing a therapeutically efficient, biocompatible administration route [2,3]. The appeal of nanoparticles (NPs) extends to their size, relative biosafety and multi-functionality that can be adapted for disease-specific models [4,5] They are optimally designed to cross physiological barriers with ease, are classed as generally immunological compliant, and can access a variety of tissues [6,7]. They allow for the reformulation and stabilisation of toxic drugs, diagnostic elements, and corrective genes, making them clinically and commercially beneficial [4].
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