pH-Responsive Micellar Nanoparticles for the Delivery of a Self-Amplifying ROS-Activatable Prodrug.

The objective of this study is to enhance the therapeutic efficacy of the anticancer drug, camptothecin (CPT) via a nanoparticle (NP) formulation using a novel amphiphilic biopolymer. We have designed a dimeric prodrug of CPT with the ability to self-amplify and respond to reactive oxygen species (ROS). For this, we incorporated the intracellular ROS generator cinnamaldehyde into a ROS-cleavable thioacetal (TA) linker to obtain the dimeric prodrug of CPT (DCPT(TA)). For its efficient NP delivery, a pH-responsive block copolymer of acetalated dextran and poly(2-ethyl-2-oxazoline) (AcDex-b-PEOz) was synthesized. The amphiphilic feature of the block copolymer enables its self-assembly into micellar NPs and results in high prodrug loading capacity and a rapid release of the prodrug under acidic conditions. Upon cellular uptake by HeLa cells, DCPT(TA)-loaded micellar NPs induce intracellular ROS generation, resulting in accelerated prodrug activation and enhanced cytotoxicity. These results indicate that this system holds significant potential as an effective prodrug delivery strategy in anticancer treatment.

Enhanced clearance of C. muridarum infection using azithromycin-loaded liposomes.

Chlamydia trachomatis is an intracellular bacterium which infects around 129 million people annually. Despite similar infection rates between sexes, most research investigating the effects of chlamydial infection on fertility has focused on females. There is now emerging evidence of a potential link between Chlamydia and impaired male fertility. The only treatments for chlamydial infection are antibiotics, with azithromycin (AZI) being one of the commonly used drugs. However, recent studies have suggested that optimizing the treatment regime is necessary, as higher concentrations of AZI may be required to effectively clear the infection in certain cell types, particularly testicular macrophages. To address this challenge, we have prepared liposomes consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) loaded with AZI for clearing Chlamydia. These liposomes exhibited stability over time and were readily taken up by both macrophages and epithelial cells. Moreover, they demonstrated significant enhancement of chlamydial clearance in both cell types. In a mouse model, the drug-loaded liposomes cleared Chlamydia within the penile urethra more efficiently than the same dose of unencapsulated drug. Furthermore, the liposome-drug treatment showed significant protective effects on sperm motility and morphology, suggesting potential benefits in reducing sperm damage caused by the infection.

Stability and antigenicity of Chlamydia muridarum major outer membrane protein antigen at body temperature.

Chlamydia is an obligate intracellular bacterial pathogen responsible for disease and infertility across multiple species. Currently vaccines are being studied to help reduce the prevalence of this disease. The main advantage of protein subunit vaccines is their high degree of safety although this is traded off with the requirement for multiple booster doses to achieve complete protection. Although in certain populations the booster dose can be difficult and costly to administer, development of delayed vaccine delivery techniques, such as a vaccine capsule, could be the solution to this problem. One of the main drawbacks in this technology is that the antigen must remain stable at body temperature (37 °C) until release is achieved. Here we elucidate the stability of a recombinant chlamydial major outer membrane protein (MOMP) antigen and assess its antigenic and immunogenic properties after subjecting the antigen to 37 °C for four to six weeks. Through in vitro and in vivo assessment we found that the aged chlamydial MOMP was able to produce equivalent humoral and cell-mediated immune responses when compared with the unaged vaccine. It was also found that vaccines formulated with the aged antigen conferred equivalent protection against a live infection challenge as the unaged antigen. Thus ageing chlamydial MOMP antigens at 37 °C for four to six weeks did not cause any significant structural or antigenic/immunogenic degradation and recombinant C. muridarum MOMP is suitable for use in a delayed vaccine delivery system.