Should Trackable Pill Technologies Be Used to Facilitate Adherence Among Patients Without Insight?

Aripiprazole tablets with sensor offer a new wireless trackable form of aripiprazole that represents a clear departure from existing drug delivery systems, routes, or formulations. This tracking technology raises concerns about the ethical treatment of patients with psychosis when it could introduce unintended treatment challenges. The use of "trackable" pills and other "smart" drugs or nanodrugs assumes renewed importance given that physicians are responsible for determining patients' decision-making capacity. Psychiatrists are uniquely positioned in society to advocate on behalf of vulnerable patients with mental health disorders. The case presented here focuses on guidance for capacity determination and informed consent for such nanodrugs.

Albendazole-lipid nanocapsules: Optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus granulosus.

Cystic echinococcosis (CE), which is caused during the metacestode larval stage of Echinococcus granulosus, is a life-threatening disease and is very difficult to treat. At present, the FDA-approved antihelmintic drugs are mebendazole (MBZ), albendazole (ABZ) and its principal metabolite ABZ sulfoxide (ABZSO), but as these have a therapeutic efficacy over 50%, underlining the need for new drug delivery systems. The aim of this work was the optimization and characterization of previously developed ABZ lipid nanocapsules (ABZ-LNCs) and evaluate their efficacy in mice infected with E. granulosus. LNCs were prepared by the phase inversion technique and characterized in terms of size, surface charge, drug loading, and in vitro stability followed by an in vivo proof-of-concept using a murine model infected with E. granulosus. Stable particle dispersions with a narrow size distribution and high efficiency of encapsulation (≥90%) were obtained. ABZ-LNCs showed a greater chemoprophylactic efficacy than ABZ suspension administered by the oral route as 4 out of the 10 ABZ-LNCs treated mice did not develop any cysts, whereas the infection progressed in all mice from the ABZ suspension group. Regarding the ultrastructural studies of cysts, mice treated with ABZ-LNCs or ABZ suspension revealed changes in the germinal layer. However, the extent of the damage appeared to be greater after ABZ-LNC administration compared to the suspension treatment. These results suggest that ABZ-LNCs could be a promising novel candidate for ABZ delivery to treat CE.

Importance of Encapsulation Stability of Nanocarriers with High Drug Loading Capacity for Increasing in Vivo Therapeutic Efficacy.

Current drug delivery systems are hampered by poor delivery to tumors, in part reflecting poor encapsulation stability of nanocarriers. Although nanocarriers such as polymeric micelles have high colloidal stability and do not aggregate or precipitate in bulk solution, nanocarriers with low encapsulation stability can lose their cargo during circulation in blood due to interactions with blood cells, cellular membranes, serum proteins, and other biomacromolecules. The resulting premature drug release from carriers limits the therapeutic efficacy at target sites. Herein, we report a simple and robust technique to improve encapsulation stability of drug delivery systems. Specifically, we show that installation of disulfide cross-linked noncovalent polymer gatekeepers onto mesoporous silica nanoparticles with a high loading capacity for hydrophobic drugs enhances in vivo therapeutic efficacy by preventing premature release of cargo. Subsequent release of drug cargos was triggered by cleavage of disulfide cross-linking by glutathione, leading to improved antitumor activity of doxoroubicin in mice. These findings provide novel insights into the development of nanocarriers with high encapsulation stability and improved in vivo therapeutic efficacy.

PLGA nanoparticles stabilized with cationic surfactant: safety studies and application in oral delivery of paclitaxel to treat chemical-induced breast cancer in rat.

PURPOSE: This study was carried out to formulate poly(lactide-co-glycolide) (PLGA) nanoparticles using a quaternary ammonium salt didodecyl dimethylammonium bromide (DMAB) and checking their utility to deliver paclitaxel by oral route. METHODS: Particles were prepared by emulsion solvent diffusion evaporation method. DMAB and particles stabilized with it were evaluated by MTT and LDH cytotoxicity assays. Paclitaxel was encapsulated in these nanoparticles and evaluated in a chemical carcinogenesis model in Sprague Dawley rats. RESULTS: MTT and LDH assays showed the surfactant to be safe to in vitro cell cultures at concentrations <33 microM. PLGA nanoparticles prepared using this stabilizer were also found to be non-toxic to cell lines for the duration of the study. When administered orally to rats bearing chemically induced breast cancer, nanoparticles were equally effective/better than intravenous paclitaxel in cremophor EL at 50% lower dose. CONCLUSIONS: This study proves the safety and utility of DMAB in stabilizing preformed polymers like PLGA resulting in nanoparticles. This preliminary data provides a proof of concept of enabling oral chemotherapy by efficacy enhancement for paclitaxel.