Antibody-decorated chitosan-iodoacetamide-coated nanocarriers for the potential delivery of doxorubicin to breast cancer cells.

Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti-HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.

Optimization of In Situ Gel-Forming Chlorhexidine-Encapsulated Polymeric Nanoparticles Using Design of Experiment for Periodontitis.

Periodontitis is a chronic inflammatory disease of the gums caused by pathogenic microorganisms damaging and destroying periodontal tissues. Chlorhexidine digluconate (CHX) is a commonly used antimicrobial agent for the treatment of periodontitis. However, it has many drawbacks, such as toxicity due to the high dosage required, low prolonged release, and low adhesion in the periodontal pocket. The objective of this study was to develop and optimize CHX-encapsulated polymeric nanoparticles (NPs) loaded into in situ gel-forming (ISGF) using design of experiment (DoE) to improve the treatment of periodontitis and overcome these limitations. CHX-NPs were optimized from 0.046%w/v chitosan, 0.05%w/w gelatin, and 0.25%w/w CHX. After that, the optimized of CHX-NPs was loaded into a thermosensitive ISGF, which was a mixture of 15%w/v Poloxamer 407 and 1% hydroxypropyl methylcellulose (HPMC). The optimized CHX-NPs, loaded into ISGF, was evaluated by measuring gelling temperature and time, pH, viscosity, compatibility, in vitro drug release, antibacterial activity, cytotoxicity, and stability. The results showed that the size, PDI, and zeta potential of optimized CHX-NPs were 53.07±10.17 nm, 0.36±0.02, and 27.63±4.16 mV, respectively. Moreover, the optimized ISGF loading CHX-NPs showed a gelling temperature at 34.3±1.2°C within 120.00±17.32 s with a pH value of 4.06. The viscosity of the formulations at 4°C was 54.33±0.99 cP. The DSC and FTIR showed no interaction between ingredients. The optimal formulations showed a prolonged release of up to 7 days while providing potential antibacterial activity and were safe for normal gingival fibroblast cells. Moreover, the formulations had high stability at 4°C and 25°C for 3 months. In conclusion, the study achieved the successful development of ISGF loading CHX-NPs formulations for effectiveness use in periodontal treatment.

Catechol-Functionalized Alginate Nanoparticles as Mucoadhesive Carriers for Intravesical Chemotherapy.

This research aimed to synthesize and evaluate mucoadhesive catechol-functionalized alginate (Cat-Alg) nanoparticles (NPs) for bladder cancer. Cat-Alg was synthesized using coupling chemistry, and the structure was verified using NMR and FT-IR. Cat-Alg NPs were generated by ionic gelation between the synthesized Cat-Alg and calcium chloride. Garcinia mangostana L. extract (GM extract) was entrapped into the NPs during particle formation. The physical characteristics, mucoadhesive properties, drug loading and release, cellular uptake, and anticancer activity of the GM extract-loaded NPs were investigated. The Cat-Alg NPs were spherical with sizes in the range of 155-186 nm. The slightly negative surface charge of the NPs provided them with excellent stability. The Cat-Alg NPs could be retained on a porcine bladder mucosa to a greater extent compared with unmodified Alg NPs. High loading efficiency (71.6%) and loading capacity (292 µg/mg) of GM extract in the NPs were achieved, and a constant release of GM extract was obtained for up to 8 h with zero-order kinetics. Moreover, the GM extract-loaded NPs were deposited in bladder tissue and accumulated in MB49 cells at a higher rate compared with GM extract suspension. In addition, the NPs could kill a mouse urothelial carcinoma cell line with low IC50. Therefore, these NPs have the potential to be a mucoadhesive drug delivery system for bladder cancer treatment. However, additional in vivo investigations are needed for clinical application in cancer treatment. Graphical abstract.

6-Maleimidohexanoic acid-grafted chitosan: A new generation mucoadhesive polymer.

This study aims to synthesize and evaluate a new generation mucoadhesive polymer, 6-maleimidohexanoic acid-grafted chitosan; MHA-CS, for transmucosal drug delivery compared with a well-known mucoadhesive polymer, Cys-CS. The successful synthesis was confirmed by nuclear magnetic resonance (NMR) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy. Gel permeation chromatography (GPC) was used to determine the molecular weight of the synthesized polymer. The quantity of maleimide on the polymer chain as well as the mucoadhesive properties and biocompatibility of the synthesized polymers were also assessed. The results revealed that the synthesized MHA-CS demonstrated excellent mucoadhesive properties which is superior to CS and Cys-CS. The maleimide content bound to synthesized polymer was 466 µmol per gram of the polymer. The cytotoxicity test assured the low toxicity of the synthesized polymer on the normal human gingival fibroblast cells. These data support the potential of MHA-CS as a novel material for developing mucoadhesive drug delivery system with enhanced mucoadhesive properties.