Chitosan Derivatives with Mucoadhesive and Antimicrobial Properties for Simultaneous Nanoencapsulation and Extended Ocular Release Formulations of Dexamethasone and Chloramphenicol Drugs

Abstract

The aim of this work was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with 2-acrylamido-2-methyl-1-propanesulfonic acid (AAMPS) and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSP) as appropriate nanocarriers for the simultaneous ocular administration of dexamethasone sodium phosphate (DxP) and chloramphenicol (CHL). The derivatives CS-AAMPS and CS-MEDSP have been synthesized by free-radical polymerization and their structure has been proved by Fourier-Transformed Infrared Spectroscopy (FT-IR) spectroscopy. Both derivatives exhibited low cytotoxicity, enhanced mucoadhesive properties and antimicrobial activity against Staphylococcus aureus (S.aureus) and Escherichia coli (E. coli). Encapsulation was performed via ionic crosslinking gelation using sodium tripolyphosphate (TPP) as the crosslinking agent. Dynamic light scattering measurements (DLS) showed that the prepared nanoparticles had bimodal distribution and sizes ranging from 50–200 nm and 300–800 nm. Drugs were encapsulated in their crystalline (CHL) or amorphous (DexSP) form inside nanoparticles and their release rate was dependent on the used polymer. The CHL dissolution rate was substantially enhanced compared to the neat drug and the release time was extended up to 7 days. The release rate of DexSP was much faster than that of CHL and was prolonged up to 3 days. Drug release modeling unveiled that diffusion is the main release mechanism for both drugs. Both prepared derivatives and their drug-loaded nanoparticles could be used for extended and simultaneous ocular release formulations of DexSP and CHL drugs.

Leflunomide Sustained Skin Delivery Based on Sulfobetaine-Modified Chitosan Nanoparticles Embedded in Biodegradable Polyesters Films

“…These findings indicate that the newly prepared polymer is slightly more hydrophilic than the neat CS, a feature attributed to the additional reactive groups of SDAEM embedded in the CS backbone chain. This finding is in agreement with swelling results reported previously; however, it is important to note that compared to those reports, the utilization of higher amounts of SDAEM [ 40 , 51 ] leads to a significantly lower enhancement of CS’s swelling ability, as the results in the present study show. This reduction in hydrophilicity may compromise the material’s skin adhesion ability; however, in contrast to the previous reports, the obtained drug-loaded NPs, resulting from the SDAEM-modified CS, will be embedded into a thin-film patch prepared by aliphatic polyesters (mPEG-b-PLA or PLGA), which have excellent skin adhesive properties on their own, and hence it is anticipated that the reduction in adhesion coming from the low SDAEM concentration will be compensated by the presence of the polyester matrix.…”

“…Additionally, in the case of CS-SDAEM, a small shoulder was recorded at 3431 cm −1 (attributed to the -OH vibrations of CS), two peaks at 3357 and 3294 cm −1 (attributed to hydrogen bonded –OH groups and primary amino groups, respectively), a small shoulder at 3084 cm −1 (due to the secondary amino groups), a small peak at 1720 cm −1 and another at 1650 cm −1 (due to the ester groups of CS), a small peak at 1200 cm −1 (attributed to the SO 3 − group vibrations), and a strong peak at 1027 cm −1 (attributed to the C–N absorption vibrations). These peaks, and especially the new peak at 1720 cm −1 corresponding to the ester group of the monomer, which is in agreement with previous results [ 40 , 51 ], indicate the successful grafting of CS and the formation of a CS-SDAEM, as well as the formation of intermolecular interactions (probably hydrogen bonds, HBs) between the reactive groups of the SDAEM monomer (–CO–O and SO 3 – ) and the -NH 2 or the –OH groups of CS.…”

“…In regard to the newly derived CS-SDAEM, results showed that this is also semi-crystalline in nature, with a characteristic amorphous halo and a single broad pXRD peak at 20.1 deg. It should be noted that, compared to previous results utilizing SDAEM at higher concentrations [40,51], the resultant CS-SDAEM polymer in the present study showed a similar degree of crystallinity as compared to the neat CS, indicating that at such low concentrations, SDAEM is not adequate enough to reduce CS's ability to fold and create crystallites.…”

Chitosan Nanoparticles-Insight into Properties, Functionalization and Applications in Drug Delivery and Theranostics

“…Thiolation leads to increase in mucoadhesion of chitosan by creating strong interaction (disulphide bonds) between the thiol groups and the cysteine region of the mucous glycoprotein. The functionalized derivatives of chitosan: trimethyl chitosan, carboxymethyl chitosan have been reported to enhance the mucoadhesive properties [ 7 ].…”

Polysaccharide-Based Nanomaterials for Ocular Drug Delivery: A Perspective

“…Nanoparticles, nanocapsules, and nanomicelles are typical zero-dimensional drug carriers; nanoparticles are characterized by a uniform distribution of the drug and carrier, while the drug in the latter two is encapsulated in the carrier core. These nanomaterials improve the drug solubility and enhance the corneal penetration with prolonged retention times ( Liu et al, 2019 ; Karava et al, 2020 ). One-dimensional polysaccharide-based nanomaterials are often used as excipients for their plasticity and low-encapsulation efficiency.…”