Preparation of mucoadhesive methacrylated chitosan nanoparticles for delivery of ciprofloxacin.

Mucoadhesive polymers and their nanoparticles have attracted a lot of attention in pharmaceutical applications, especially transmucosal drug delivery (TDD). Mucoadhesive polysaccharide-based nanoparticles, particularly chitosan, and its derivatives, are widely used for TDD owing to their outstanding features such as biocompatibility, mucoadhesive, and absorption-enhancing properties. Herein, this study aimed to design potential mucoadhesive nanoparticles for the delivery of ciprofloxacin based on methacrylated chitosan (MeCHI) using the ionic gelation method in the presence of sodium tripolyphosphate (TPP) and compared them with the unmodified chitosan nanoparticles. In this study, different experimental conditions including the polymer to TPP mass ratios, NaCl, and TPP concentration were changed to achieve unmodified and MeCHI nanoparticles with the smallest particle size and lowest polydispersity index. At 4:1 polymer /TPP mass ratio, both chitosan and MeCHI nanoparticles had the smallest size (133 ± 5 nm and 206 ± 9 nm, respectively). MeCHI nanoparticles were generally larger and slightly more polydisperse than the unmodified chitosan nanoparticles. Ciprofloxacin-loaded MeCHI nanoparticles had the highest encapsulation efficiency (69 ± 13 %) at 4:1 MeCHI /TPP mass ratio and 0.5 mg/mL TPP, but similar encapsulation efficiency to that of their chitosan counterpart at 1 mg/mL TPP. They also provided a more sustained and slower drug release compared to their chitosan counterpart. Additionally, the mucoadhesion (retention) study on sheep abomasum mucosa showed that ciprofloxacin-loaded MeCHI nanoparticles with optimized TPP concentration had better retention than the unmodified chitosan counterpart. The percentage of the remained ciprofloxacin-loaded MeCHI and chitosan nanoparticles on the mucosal surface was 96 % and 88 %, respectively. Therefore, MeCHI nanoparticles have an excellent potential for applications in drug delivery.

Mucus-penetrating nanoparticles based on chitosan grafted with various non-ionic polymers: Synthesis, structural characterisation and diffusion studies.

Transmucosal administration offers numerous advantages for drug delivery as it usually helps to avoid first pass metabolism, provides rapid onset of action, and is a non-invasive route. Mucosal surfaces are covered by a viscoelastic mucus gel layer which acts as a protective barrier preventing the entrance of harmful substances into the human tissues. This function of mucus also inhibits the diffusion of drugs and nano-formulations and can result in a significant reduction of their efficacy. The design of mucus-penetrating nanoparticles can overcome the barrier function of mucus which may lead to better therapeutic outcomes. In this study, chitosan was chemically modified by grafting short chains of poly(ethylene glycol), poly(2-hydroxyethyl acrylate), poly(2-ethyl-2-oxazoline), or poly(N-vinyl pyrrolidone) and the resulting chitosan derivatives were used to prepare nanoparticles using an ionic gelation method with sodium tripolyphosphate. These nanoparticles were characterised using dynamic light scattering, transmission electron microscopy, small-angle neutron scattering and nanoparticle tracking analysis. Small-angle neutron scattering data revealed the presence of a large amount of water inside these nanoparticles and lack of a heterogeneous internal structure. The nanogel model with low crosslinking density is suggested as the most feasible model to describe the structure of these nanoparticles. The studies of the behaviour of these nanoparticles in bovine submaxillary mucin solutions and their penetration into sheep nasal mucosa indicated greater diffusivity of modified chitosan nanoparticles compared to unmodified chitosan nanoparticles with the best results achieved for the chitosan grafted with poly(N-vinyl pyrrolidone).

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 ±â€¯1, 68 ±â€¯1 and 59 ±â€¯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.