Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles

There are very few drug delivery systems that target key organs via the oral route, as oral delivery advances normally address gastrointestinal drug dissolution, permeation, and stability. Here we introduce a nanomedicine in which nanoparticles, while also protecting the drug from gastric degradation, are taken up by the gastrointestinal epithelia and transported to the lung, liver, and spleen, thus selectively enhancing drug bioavailability in these target organs and diminishing kidney exposure (relevant to nephrotoxic drugs). Our work demonstrates, for the first time, that oral particle uptake and translocation to specific organs may be used to achieve a beneficial therapeutic response. We have illustrated this using amphotericin B, a nephrotoxic drug encapsulated within <i>N</i>-palmitoyl-<i>N</i>-methyl-<i>N</i>,<i>N</i>-dimethyl-<i>N</i>,<i>N</i>,<i>N</i>-trimethyl-6-<i>O</i>-glycol chitosan (GCPQ) nanoparticles, and have evidenced our approach in three separate disease states (visceral leishmaniasis, candidiasis, and aspergillosis) using industry standard models of the disease in small animals. The oral bioavailability of AmB-GCPQ nanoparticles is 24%. In all disease models, AmB-GCPQ nanoparticles show comparable efficacy to parenteral liposomal AmB (AmBisome). Our work thus paves the way for others to use nanoparticles to achieve a specific targeted delivery of drug to key organs via the oral route. This is especially important for drugs with a narrow therapeutic index

Peroral Amphotericin B Polymer Nanoparticles Lead to Comparable or Superior In Vivo Antifungal Activity to That of Intravenous Ambisome® or Fungizone™

Background: Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70–90%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical. Methodology: Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs) were developed for oral administration. The AMB-NPs were 113±20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery. Conclusions: The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™and responds only modestly to AmBisome®

Occupational concerns associated with regular use of microscope

Objectives: Microscope work can be strenuous both to the visual system and the musculoskeletal system. Lack of awareness or indifference towards health issues may result in microscope users becoming victim to many occupational hazards. Our objective was to understand the occupational problems associated with regular use of microscope, awareness regarding the hazards, attitude and practice of microscope users towards the problems and preventive strategies. Material and Methods: A questionnaire based survey done on 50 professionals and technicians who used microscope regularly in pathology, microbiology, hematology and cytology laboratories. Results: Sixty two percent of subjects declared that they were suffering from musculoskeletal problems, most common locations being neck and back. Maximum prevalence of musculoskeletal problems was noted in those using microscope for 11–15 years and for more than 30 h/week. Sixty two percent of subjects were aware of workplace ergonomics. Fifty six percent of microscope users took regular short breaks for stretching exercises and 58% took visual breaks every 15–30 min in between microscope use sessions. As many as 94% subjects reported some form of visual problem. Fourty four percent of microscope users felt stressed with long working hours on microscope. Conclusions: The most common occupational concerns of microscope users were musculoskeletal problems of neck and back regions, eye fatigue, aggravation of ametropia, headache, stress due to long working hours and anxiety during or after microscope use. There is an immediate need for increasing awareness about the various occupational hazards and their irreversible effects to prevent them

The specific inherent optical properties of three sub-tropical and tropical water reservoirs in Queensland, Australia

The underwater light climate, which is a major influence on the ecology of aquatic systems, is affected by the absorption and scattering processes that take place within the water column. Knowledge of the Specific Inherent Optical Properties (SIOPs) of water quality parameters and their spatial variation is essential for the modelling of underwater light fields and remote sensing applications. We measured the SIOPs and water quality parameter concentrations of three large inland water impoundments in Queensland, Australia. The measurements ranged from 0.9–42.7 μgl/1 for chlorophyll a concentration, 0.9–170.4 mgl/1 for tripton concentration, 0.36–1.59 m/1 for aCDOM(440) and 0.15–2.5 m for Secchi depth. The SIOP measurements showed that there is sufficient intra-impoundment variation in the specific absorption and specific scattering of phytoplankton and tripton to require a well distributed network of measurement stations to fully characterise the SIOPs of the optical water quality parameters. While significantly different SIOP sets were measured for each of the study sites the measurements were consistent with published values in other inland waters. The multiple measurement stations were allocated into optical domains as a necessary step to parameterise a semi-analytical inversion remote sensing algorithm. This paper also addresses the paucity of published global inland water SIOP sets by contributing Australian SIOP sets to allow international and national comparison

Biodegradable nanoparticles improve oral bioavailability of Amphotericin B and shows reduced nephrotoxicity against intravenous Fungizone®

Amphotericin B (AMB), an effective antifungal and antileishmanial agent associated with low oral bioavailability (0.3%) and severe nephrotoxicity, was entrapped into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve the oral bioavailability and to minimize the adverse effects associated with it. The AMB-nanoparticles (AMB-NP) were prepared by nanoprecipitation method employing Vitamin E-TPGS as a stabilizer. In vitro release was carried out using membrane dialysis method. The in vitro hemolytic activity of AMB-NP was evaluated by incubation with red blood cells (RBCs). The acute nephrotoxicity profile and oral bioavailability of AMB-NP were evaluated in rats. The prepared AMB-NP formulation contained monodispersed particles in the size range of 165.6 ± 2.9 nm with 34.5 ± 2.1% entrapment at 10% w/w initial drug loading. AMB-NP formulation showed biphasic drug release, an initial rapid release followed by a sustained release. The AMB-NP formulation exerted lower hemolysis and nephrotoxicity as compared to Fungizone®. The relative oral bioavailability of the AMB-NP was found to be ∼800% as compared to Fungizone®. Together, these results offer a possibility of treating systemic fungal infection and leishmaniasis with oral AMB-NP, which could revolutionize the infectious disease treatment modalities