Thiolated Silica Nanoparticles Research Articles

Thiolated and PEGylated silica nanoparticle delivery to hair follicles.

Targeting drug delivery to hair follicles is valuable to treat conditions such as alopecia's and acne, and this shunt route may also allow drug delivery to deeper skin layers and the systemic circulation by avoiding the intact stratum corneum. Here, we investigated the effects of nanoparticle surface chemistry on their delivery into hair follicles by synthesizing fluorescent thiolated silica nanoparticles and functionalizing with 750Da and 5000Da methoxypolyethylene glycol maleimide (PEG). The stability of the nanoparticles in skin homogenate was verified before tape stripping of porcine-dosed tissue showed the distribution of the free fluorescent dye and different nanoparticles in the skin. Analysis of microscopic images of the skin sections revealed penetration of nanoparticles functionalized with PEG into the appendages whereas thiolated nanoparticles stayed on the surface of the skin and were removed by tape stripping. Nanoparticles functionalized with PEG 5000Da penetrated deeper into the hair follicles compared to counterparts functionalized with PEG 750Da. PEGylation can thus enhance targeted delivery of nanoparticulates into hair follicles.

Synthesis of thiolated, PEGylated and POZylated silica nanoparticles and evaluation of their retention on rat intestinal mucosa in vitro

In this study, we synthesised thiolated silica nanoparticles using 3-mercaptopropyltrimethoxysilane and functionalised them with either 5 kDa methoxy polyethylene glycol maleimide (PEG) or 5 kDa alkyne-terminated poly(2-ethyl-2-oxazoline) (POZ). The main objectives of this study are to investigate the effects of pH on the size and ξ-potential of these nanoparticles and evaluate their mucoadhesive properties ex vivo using rat intestinal mucosa. The sizes of thiolated, PEGylated and POZylated silica nanoparticles were 53 ± 1, 68 ± 1 and 59 ± 1 nm, respectively. The size of both thiolated and POZylated nanoparticles significantly increased at pH ≤ 2, whereas no size change was observed at pH 2.5–9 for both these two types of nanoparticles. On the other hand, the size of PEGylated nanoparticles did not change over the studied pH range (1.5–9). Moreover, thiolated nanoparticles were more mucoadhesive in the rat small intestine than both PEGylated and POZylated nanoparticles. After 12 cycles of washing (with a total of 20 mL of phosphate buffer solution pH 6.8), a significantly greater amount of thiolated nanoparticles remained on the intestinal mucosa than FITC-dextran (non-mucoadhesive polymer, p < 0.005) and both PEGylated and POZylated nanoparticles (p < 0.05 both). However, both PEGylated and POZylated nanoparticles showed similar retention to FITC-dextran (p > 0.1 for both). Thus, this study indicates that thiolated nanoparticles are mucoadhesive, whereas PEGylated and POZylated nanoparticles are non-mucoadhesive in the ex vivo rat intestinal mucosa model. Each of these nanoparticles has potential applications in mucosal drug delivery.

Enhancing surface immobilization of bioactive molecules via a silica nanoparticle based coating.

Surface modification is of significant interest in biomaterials, biosensors, and device biocompatibility. Immobilization of bioactive or biomimetic molecules is a common method of disguising a foreign body as host tissue to decrease the foreign body response (FBR) and/or increase device-tissue integration. For example, in neural interfacing devices, immobilization of L1, a neuron-specific adhesion molecule, has been shown to increase neuron adhesion and reduce inflammatory gliosis on and around the implants. However, the activity of modified surfaces is limited by the relatively low concentration of the immobilized component, in part due to the low surface area of flat surfaces available for modification. In this work, we demonstrate a novel method for increasing the device surface area by attaching a layer of thiolated silica nanoparticles (TNPs). This coating method results in an almost two-fold increase in the immobilized L1 protein. L1 immobilized nanotextured surfaces showed a 100% increase in neurite outgrowth than smooth L1 immobilized surfaces without increasing the adhesion of astrocytes in vitro. The increased bioactivity observed in the cell assay was determined to be mainly due to the higher protein surface density, not the increase in surface roughness. In addition, we tested immobilization of a superoxide dismutase mimic (SODm) on smooth and roughened substrates. The SODm immobilized rough surfaces demonstrated an increase of 145% in superoxide scavenging activity compared to chemically matched smooth surfaces. These results not only show promise in improving biomimetic coating for neural implants, but may also improve surface immobilization efficacy in other fields such as catalysts, protein purification, sensors, and tissue engineering devices.

Structure and characterisation of hydroxyethylcellulose-silica nanoparticles.

Functionalising nanoparticles with polymers has gained much interest in recent years, as it aids colloidal stability and manipulation of surface properties. Here, polymer-coated thiolated silica nanoparticles were synthesised by self-condensation of 3-mercaptopropyltrimethoxysilane in the presence of hydroxyethylcellulose. These nanoparticles were characterised by dynamic light scattering, small angle neutron scattering, Nanoparticle Tracking Analysis, Raman spectroscopy, FT-IR spectroscopy, thermogravimetric analysis, Ellman's assay, transmission electron microscopy and cryo-transmission electron microscopy. It was found that increasing the amount of hydroxyethylcellulose in the reaction mixture increased the nanoparticle size and reduced the number of thiol groups on their surface. Additionally, by utilising small angle neutron scattering and dynamic light scattering, it was demonstrated that higher concentrations of polymer in the reaction mixture (0.5–2% w/v) resulted in the formation of aggregates, whereby several silica nanoparticles are bridged together with macromolecules of hydroxyethylcellulose. A correlation was identified between the aggregate size and number of particles per aggregate based on size discrepancies observed between DLS and SANS measurements. This information makes it possible to control the size of aggregates during a simple one-pot synthesis; a prospect highly desirable in the design of potential drug delivery systems.

Toxicity of thiolated silica nanoparticles modified with sulfobetaine methacrylate for potential use in chemotherapy drug conjugation

Toxicity of four novel Polyhedral Oligomeric Silsesquioxane (POSS) particles used in anti-cancer drug delivery Abdulmajeed Almutary, Barbara Sanderson

Adhesion of thiolated silica nanoparticles to urinary bladder mucosa: Effects of PEGylation, thiol content and particle size

Intravesical drug administration is used to deliver cytotoxic agents through a catheter to treat bladder cancer. One major limitation of this approach is poor retention of the drug in the bladder due to periodic urine voiding. Mucoadhesive dosage forms thus offer significant potential to improve drug retention in the bladder. Here, we investigate thiolated silica nanoparticles retention on porcine bladder mucosa in vitro, quantified through Wash Out50 (WO50) values, defined as the volume of liquid necessary to remove 50% of the adhered particles from a mucosal tissue. Following irrigation with artificial urine solution, the thiolated nanoparticles demonstrate significantly greater retention (WO50 up to 36mL) compared to non-mucoadhesive dextran (WO50 7mL), but have weaker mucoadhesive properties than chitosan (WO50 89mL). PEGylation of thiolated silica reduces their mucoadhesion with WO50 values of 29 and 8mL for particles decorated with 750 and 5000Da PEG, respectively. The retention of thiolated silica nanoparticles is dependent on their thiol group contents and physical dimensions.

POZylation: a new approach to enhance nanoparticle diffusion through mucosal barriers.

The increasing use of nanoparticles in the pharmaceutical industry is generating concomitant interest in developing nanomaterials that can rapidly penetrate into, and permeate through, biological membranes to facilitate drug delivery and improve the bioavailability of active pharmaceutical ingredients. Here, we demonstrate that the permeation of thiolated silica nanoparticles through porcine gastric mucosa can be significantly enhanced by their functionalization with either 5 kDa poly(2-ethyl-2-oxazoline) or poly(ethylene glycol). Nanoparticle diffusion was assessed using two independent techniques; Nanoparticle Tracking Analysis, and fluorescence microscopy. Our results show that poly(2-ethyl-2-oxazoline) and poly(ethylene glycol) have comparable abilities to enhance diffusion of silica nanoparticles in mucin dispersions and through the gastric mucosa. These findings provide a new strategy in the design of nanomedicines, by surface modification or nanoparticle core construction, for enhanced transmucosal drug delivery.