The goal of this study was the design and evaluation of a thiolated cyclodextrin providing high drug solubilizing and mucoadhesive properties for ocular drug delivery. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was thiolated via a microwave-assisted method, resulting in a degree of thiolation of 33%. Mucoadhesive properties of thiolated HP-β-CD (HP-β-CD-SH) were determined via rheological measurements and ex vivo studies on isolated porcine cornea. Due to thiolation of HP-β-CD, a 2-fold increase of mucus viscosity and a 1.4-fold increase in residence time on isolated corneal tissue were achieved. After instillation, the mean precorneal residence time and AUC of dexamethasone (DMS) eye drops were 4-fold and 11.7-fold enhanced by HP-β-CD-SH, respectively. Furthermore, in the presence of HP-β-CD-SH, a constant high level of DMS in aqueous humour between 30 and 150 min after administration was observed. These results suggest that HP-β-CD-SH is an excellent excipient for ocular formulations of poorly soluble drugs in order to prolong their ocular residence time and bioavailability.

This study was aimed to evaluate the impact of surfactants used for nanostructured lipid carriers (NLCs) to provide enzymatic protection for incorporated peptides. Insulin as a model peptide was ion paired with sodium dodecyl sulfate to improve its lipophilicity. Three NLC formulations containing polyethylene glycol ester (PEG-ester), polyethylene glycol ether (PEG-ether), and polyglycerol ester (PG-ester) surfactants were prepared by solvent diffusion method. NLCs were characterized regarding particle size, polydispersity index, and zeta potential. Biocompatibility of NLCs was assessed on Caco-2 cells via resazurin assay. In vitro lipolysis study was performed using a standard lipid digestion method. Proteolytic studies were performed in simulated gastric fluid containing pepsin and simulated intestinal fluid containing pancreatin. Lipophilicity of insulin in terms of log P_{octanol/water} was improved from −1.8 to 2.1. NLCs were in the size range of 64–217 nm with a polydispersity index of 0.2–0.5 and exhibited a negative surface charge. PG-ester NLCs were non-cytotoxic up to a concentration of 0.5%, PEG-ester NLCs up to a concentration of 0.25% and PEG-ether NLC up to a concentration of 0.125% (w/v). The lipolysis study showed the release of >90%, 70%, and 10% of free fatty acids from PEG-ester, PG-ester, and PEG-ether NLCs, respectively. Proteolysis results revealed the highest protective effect of PEG-ether NLCs followed by PG-ester and PEG-ester NLCs for incorporated insulin complex. Findings suggest that NLCs bearing substructures less susceptible to degrading enzymes on their surface can provide higher protection for incorporated peptides toward gastrointestinal proteases.