The oral administration of water-soluble chemotherapeutical agents is limited by their serious gastrointestinal side effects, instability at intestinal pH, and poor absorption. Aiming to solve these problems, we chose topotecan (TPT) as a model drug and developed a novel lipid formulation containing core-shell lipid nanoparticle (CLN) that makes the water-soluble drug to ‘dissolve’ in oil. TPT molecules can be encapsulated into nanoparticles surrounded by oil barrier while avoiding the direct contact with intestinal environment, thus easing the intestinal hydrolytic degradation and gastrointestinal (GI) irritation. Microstructure and mean particle size of TPT-CLN were characterized by Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS), respectively. The average size of nanoparticles was approximately 60 nm with a homogeneous distribution in shapes of spheres or ellipsoid. According to in vitro stability studies, more initial form of TPT was observed in presence of lipid nanoparticle compared with free topotecan solution in artificial intestinal juice (pH 6.5). After oral administration of TPT-CLN in rats, AUC and C_max of TPT were all increased compared with free TPT, indicating significant enhancement of oral absorption. Intestinal lymphatic transport was confirmed as the major way for CLN to enhance oral absorption of TPT by the treatment of blocking chylomicron flow. Lower GI irritation of TPT-CLN was observed in the gastrointestinal damage studies. The in vivo antitumor activity of TPT-CLN showed an improved antitumor efficacy by oral treatment of TPT-CLN compared to free TPT. From the obtained data, the systems appear an attractive progress in oral administration of topotecan.

Local chemotherapy is an alternative therapeutic strategy that involves direct delivery of drugs to the tumor site. This approach avoids adverse reactions caused by the systemic distribution of drugs and enhances the tumor-suppressing effect by concentrating the drugs at the tumor site. Drug-loaded microspheres are injectable sustained-release drug carriers that are highly suitable for local chemotherapy. However, a complex preparation process is one of the main technical difficulties limiting the development of microsphere formulations. In this study, core-shell structured microspheres loaded with paclitaxel (PTX; with a core-shell structure, calcium alginate outer layer, and a poly (lactic acid-co-glycolic acid) copolymer inner layer, denoted as PTX-CA/PLGA-MS) were prepared using coaxial electrostatic spray technology and evaluated in vitro and in vivo. PTX-CA/PLGA-MS exhibited a two-stage drug release profile and enhanced anti-tumor effect in animal tumor models. Importantly, the preparation method reported in this study is simple and reduces the amount of organic solvent(s) used substantially.

Bacterial infection has always been one of the most serious threats faced by humans. Bacterial targeting is a promising strategy to enhance treatment efficacy and reduce the emergence of drug resistance. However, the traditional antibiotic targeting efficiency is poor, and it is challenging to achieve therapeutic concentrations of both drugs simultaneously in the same tissue due to differences in drug metabolism. This study aims to construct bacteria-targeted liposomes to enhance antibiotic delivery. In this study, anionic liposomes were constructed using the thin-film dispersion method, and the cationic antimicrobial peptide polymyxin B (PMB) was adsorbed onto the liposome surface through anionic-cationic electrostatic interaction as a carrier for fosfomycin (FOS), enabling bacteria-targeted drug delivery. The targeted effect of polymyxin B liposomes (PMB-Lipo) on Acinetobacter baumannii was evaluated in vitro and in vivo. The bactericidal activity of polymyxin B adsorbed fosfomycin liposomes (PMB-FOS-Lipo) in vitro and in vivo was compared with PMB and FOS mixture solution (PMB-FOS-Solution), and the anti-infection and anti-inflammatory effects were assessed. We also explored the issue of PMB nephrotoxicity using a series of biochemical indicators in mice. In vitro and in vivo experiments showed that PMB-Lipo effectively targeted Acinetobacter baumannii. PMB-FOS-Lipo exhibited better therapeutic efficacy compared to free PMB and FOS. Finally, adsorbing polymyxin B onto the liposome surface significantly reduced its severe nephrotoxicity. PMB-Lipo can effectively target Acinetobacter baumannii, and the encapsulated fosfomycin in liposomes synergizes with polymyxin B, enhancing antibacterial efficacy and reducing adverse drug reactions. We believe this antibacterial strategy can provide new insights into bacteria-targeted treatment.

The increasing prevalence of wound infections caused by multidrug-resistant Gram-negative bacteria, particularly carbapenem-resistant Acinetobacter baumannii (CRAB), necessitates novel therapeutic strategies to overcome the limitations of single-agent treatments. This study presents a synergistic treatment strategy by co-delivering bacteriophages and polymyxin B loaded within a poloxamer F127-based thermosensitive hydrogel. Sodium hyaluronate (HA) was incorporated to improve the poor viscoelasticity of the pure F127 hydrogel at low temperatures, thereby enabling practical handling without compromising its thermogelling properties. In a mouse model of full-thickness wounds infected with CRAB, the hydrogel-treated group exhibited significantly accelerated wound closure and improved histopathological outcomes compared to those observed in the controls receiving monotherapies or a blank hydrogel. This study establishes a practical and effective co-delivery platform that combines enhanced material properties with a potent synergistic antimicrobial strategy for managing complex resistant wound infections.