pH-temperature dual-sensitive nucleolipid-containing stealth liposomes anchored with PEGylated AuNPs for triggering delivery of doxorubicin.

Liposomes (Lip) are useful nanocarriers for drug delivery and cancer nanomedicine because of their ability to efficiently encapsulate drugs with different physical and chemical properties. The pH gradient between normal and tumoral tissues, and their rapid metabolism that induces hyperthermia encourage the development of pH- and thermo-sensitive Lip for delivering anticancer drugs. Nucleolipids have been studied as scaffolding material to prepare Lip, mainly for cancer therapy. Herein, we report for the first time the use of 1,2-dipalmitoyl-sn-glycero-3-(cytidine diphosphate) (DG-CDP) to develop pH/thermo-sensitive nucleolipid-containing stealth Lip stabilized by combination with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol, anchored with NH2-PEGylated gold nanoparticles (PEG-AuNPs, 15 nm) for triggering delivery of doxorubicin (Dox). The optimal composition of DPPC, DG-CDP and cholesterol (94:3:3) was established by Langmuir isotherms. Unloaded and Dox-loaded Lip and AuNPs-Lip exhibited nano-scale sizes (415-650 nm), acceptable polydispersity indexes (<0.33), spherical shapes, and negative Z-potential (-23 to -6.6 mV) due to the phosphate groups of DG-CDP, which allowed the anchoring with positively charged AuNPs. High EE% were achieved (>78%) and although efficient control in the Dox release towards different receptor media was observed, the release of Dox from PEG-AuNPs-Lip-Dox was significantly triggered at acidic pH and hyperthermia conditions, demonstrating its responsiveness to both stimuli. Dox-loaded Lip showed high cytotoxic activity against MDA-MB-231 breast cancer cells and SK-OV-3 ovarian cancer cells, suggesting that Dox was released from these nanocarriers over time. Overall, the liposomal formulations showed promising properties as stimuli-responsive nanocarriers for cancer nanomedicine, with prospects for hyperthermia therapy.

Multiple brain abscesses caused by Fusobacterium nucleatum treated conservatively.

BACKGROUND: Multiple brain abscesses are serious neurological problems with high mortality and disabling morbidity. The frequency is rising as a result of AIDS and the increasing number of immunocompromised patients. CASE STUDY: A 59-year-old woman developed signs and symptoms of diffuse brain dysfunction including fever and neck stiffness. A brain CT scan demonstrated nine contrast-enhancing ring-shaped lesions. Analysis of the cerebrospinal fluid using PCR-technique revealed DNA of Fusobacterium nucleatum. Conservative treatment with antibiotics was successful. The patient recovered with only mild cognitive deficits. RESULTS: The experience of our patient and the review of the literature indicate that multiple brain abscesses due to Fusobacterium nucleatum are rare. The most probable source is oral infection. CONCLUSION: Multiple brain abscesses may be caused by Fusobacterium nucleatum. Cerebrospinal fluid analysis using PCR technique is helpful with diagnosis. Conservative management can be successful.