Enhanced stability and clinical absorption of a form of encapsulated vitamin A for food fortification.

Food fortification is an effective strategy to address vitamin A (VitA) deficiency, which is the leading cause of childhood blindness and drastically increases mortality from severe infections. However, VitA food fortification remains challenging due to significant degradation during storage and cooking. We utilized an FDA-approved, thermostable, and pH-responsive basic methacrylate copolymer (BMC) to encapsulate and stabilize VitA in microparticles (MPs). Encapsulation of VitA in VitA-BMC MPs greatly improved stability during simulated cooking conditions and long-term storage. VitA absorption was nine times greater from cooked MPs than from cooked free VitA in rats. In a randomized controlled cross-over study in healthy premenopausal women, VitA was readily released from MPs after consumption and had a similar absorption profile to free VitA. This VitA encapsulation technology will enable global food fortification strategies toward eliminating VitA deficiency.

Targeted Delivery of Antibiotic Therapy to Inhibit Pseudomonas aeruginosa Using Lipid-Coated Mesoporous Silica Core-Shell Nanoassembly.

Pseudomonas aeruginosa (PA) is an opportunistic pathogen, which causes serious lung infections in immunocompromised patients. Traditional oral intake of large quantities of small-molecule antibiotics to treat bacterial infections leads to off-target toxicity and development of drug-resistant species. Improved delivery systems of antibiotics to the targeted site of bacterial infections would help reduce the need for a high intake of antibiotics. Colistin (Col), an antibacterial peptide, is considered the last resort treatment for multidrug resistant (MDR)-PA. To approach the problem of development of antibacterial resistance and off-target toxicity due to the use of excessive amounts of antibiotics, we have designed a targeted drug delivery nanoassembly, which delivers antibiotics to extracellular and intracellular bacteria. The nanoassembly is composed of (1) drug (Col)-loaded mesoporous silica (MSN) core (Col@MSN), (2) liposomal shell (Col@MSN@LL), and (3) PA-targeting LL-37 peptide (Col@MSN@LL-(LL-37)). The liposomal shell prevents premature drug release before the nanoassembly approaches the targeted bacteria. The liposome bilayer degrades upon excreted lipase present in the local environment of PA, releasing encapsulated Col. There is a significant increase in Col release (∼90% release within 40 h) in the presence of bacteria compared to the absence of bacteria (only ∼75% release after 80 h). A 6.7-fold increase in the antimicrobial efficacy of Col encapsulated in Col@MSN@LL-(LL-37) was seen compared to free Col. All studies were done using a clinical strain of PA14. Col@MSN@LL-(LL-37) successfully targets and inhibits intracellular PA14 within the lung epithelial cells. Only 7% PA14 viability is seen after treating the lung epithelial cells with Col@MSN@LL-(LL-37). No significant cytotoxicity was observed with Col@MSN@LL-(LL-37). Therefore, this discussed lipid-coated targeted nanoassembly can be considered as a successful antibiotic delivery platform.

Biocompatible Semiconductor Quantum Dots as Cancer Imaging Agents.

Approximately 1.7 million new cases of cancer will be diagnosed this year in the United States leading to 600 000 deaths. Patient survival rates are highly correlated with the stage of cancer diagnosis, with localized and regional remission rates that are much higher than for metastatic cancer. The current standard of care for many solid tumors includes imaging and biopsy with histological assessment. In many cases, after tomographical imaging modalities have identified abnormal morphology consistent with cancer, surgery is performed to remove the primary tumor and evaluate the surrounding lymph nodes. Accurate identification of tumor margins and staging are critical for selecting optimal treatments to minimize recurrence. Visible, fluorescent, and radiolabeled small molecules have been used as contrast agents to improve detection during real-time intraoperative imaging. Unfortunately, current dyes lack the tissue specificity, stability, and signal penetration needed for optimal performance. Quantum dots (QDs) represent an exciting class of fluorescent probes for optical imaging with tunable optical properties, high stability, and the ability to target tumors or lymph nodes based on surface functionalization. Here, state-of-the-art biocompatible QDs are compared with current Food and Drug Administration approved fluorophores used in cancer imaging and a perspective on the pathway to clinical translation is provided.