Enhanced anticancer activity of drug nanoparticles formulated with ß-cyclodextrin.

Camptothecin (CPT) is a potent chemotherapeutic agent that shows a broad spectrum of anticancer activities. However, it is clinically inactive because of poor aqueous solubility, rapid aqueous hydrolysis, and unexpected side effects. Three strategies have extensively been adopted to improve its dissolution rate including reduction of drug particle size to a nanoscale, use of an amorphous state, and the formation of inclusion compounds. In our study, we combined these three strategies together by constructing CPT nanoparticles by creating an inclusion complex with ß-cyclodextrin (BCD). This new CPT formulation showed a rod-like structure of nanoscaled size and with semiamorphous or amorphous CPT. These BCD-CPT nanoparticles showed improved dissolution rate, stability, dispersion, and cellular uptake. When tested on cancer cells, BCD-CPT nanoparticles showed a much higher anticancer activity (IC50=14-28 µmol/l) in comparison with free CPT (IC50>500 µmol/l) and CPT nanocrystals (IC50>200 µmol/l). In addition, BCD-CPT nanoparticles can be physically mixed with CPT nanocrystals, leading to CPT formulations with tailored drug-release profiles to achieve customized therapeutics and flexible treatments in clinics.

Amebic appendicitis: a case report.

Changing the paradigm of treatment of acute appendicitis to non-operative management can miss unusual etiologies that can only be diagnosed on pathologic analysis. Presented is a case of amebic appendicitis in which antibiotic management was dictated by post-operative pathology findings.

A new targeted delivery approach by functionalizing drug nanocrystals through polydopamine coating.

Tumor target specificity via chemotherapy is widely considered to be very effective on tumor treatment. For an ideal chemotherapeutic agent like Camptothecin (CPT) (CPT is the abbreviation for Camptothecin), improved therapeutic efficacy and high selectivity are equally important. Inspired by adhesive proteins in mussels, here we developed a novel tumor targeting peptide XQ1 grafted CPT nanocrystals with polydopamine coating as a spacer. In this study, CPT nanocrystals were coated by polymerization of dopamine that was induced by plasma-activated water under an acidic environment, and then the tumor targeting peptide was grafted onto polydopamine (PDA) (PDA is the abbreviation for polydopamine) coated CPT nanocrystals through catechol chemistry. The PDA layer had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties, improved dissolution rate and drug stability by preventing water hydrolysis. More importantly, tumor targeting peptide XQ1 facilitated a rapid cross-membrane translocation of drug nanocrystals via receptor-mediated endocytosis, leading to efficient intracellular drug delivery. Moreover, this novel drug formulation demonstrated more potent anti-cancer activity against tumor cells in comparison with free CPT and naked CPT nanocrystals and exhibited high selectivity, all of which are attributed to the tumor target specificity property and inherent pH-dependent drug release behavior.

Anti-cancer activity of camptothecin nanocrystals decorated by silver nanoparticles.

The emergence of multidrug resistant cancer phenotypes dramatically attenuates the efficiency of a variety of anti-cancer drugs. Silver nanoparticles (AgNPs) display excellent anti-cancer activity and dramatic inhibitory effect on drug resistance related proteins like P-glycoprotein (Pgp). Here we developed a novel drug nanocrystal formulation of Camptothecin (CPT), a broad spectrum anti-cancer agent, decorated by AgNPs. The resulting combinational formulation of CPT and AgNPs, named as CPT/Ag nanocrystals, demonstrated excellent dispersion properties and an improved dissolution rate, drug stability and cellular uptake rate. Because CPT nanocrystals are able to bypass Pgp recognition and AgNPs inhibit both Pgp expression and activity, CPT/Ag nanocrystals showed extreme and indiscriminate cytotoxicity against a variety of both drug sensitive and drug resistant cancer cells. Moreover, the quickly and plenty of released CPT from the CPT/Ag nanocrystals triggered by the tumor microenvironment led to a relaxed and cleavable chromatin structure, facilitating DNA damage and apoptotic potential of AgNPs that were subsequently released.