Introduction:
The benefits of mucoadhesive systems are related to the increased in situ residence and intimate contact of the delivery vehicle with the mucosa. The recent emergence of nanomedicine ...and the properties of nanoparticulate systems have created new challenges in understanding the nature and mechanisms of nanoscale mucoadhesion and in the development of methodologies for measuring its mucoadhesive potential. Even when usually regarded as an advantageous property, mucoadhesion can be an inconvenience for nanosystems, and strategies have been developed for minimizing interactions with the mucosal tissues/fluids.
Areas covered:
This article summarizes the basic concepts of mucoadhesion at the nanoscale, different techniques used for measuring the mucoadhesive potential of nanosystems and strategies for increasing/decreasing mucoadhesive interactions.
Expert opinion:
The mucoadhesion behavior of materials in bulk and at the nanoscale can significantly differ. Advances in the methodology used for studying the mucoadhesion phenomenon have contributed to its better understanding and, more importantly, the development of strategies to increase/decrease mucoadhesion. However, development of new methodologies for studying mucoadhesion at the nanoscale and the refinement of existing methodologies are still required. Also, a substantial amount of information is still lacking, particularly related to formulation issues, on how to translate lessons learnt at the bench top to the bed side.
Nanotechnology-based systems have been proposed for rectal drug delivery, often rendering promising outcomes concerning disease prophylaxis or therapeutics. However, nanocarriers often feature ...reduced colorectal retention when administered in liquid vehicles (enemas). Semi-solid platforms may be considered as alternative but usually result in limited local distribution. Thermosensitive enemas undergoing sol-gel transition just below body temperature have been used for abbreviating these issues, but the actual impact on the colorectal distribution and retention of incorporated nanosystems is not clear. We prepared and characterized a potential drug delivery platform by incorporating poly(lactic-
co
-glycolic acid)-based nanoparticles (170-180 nm mean hydrodynamic diameter) into a poloxamer 407-based thermosensitive enema (NPs-in-thermo). The system featured suitable functional properties for rectal administration such as sol-gel transition temperature of approximately 27-28 °C, sol-gel transition time of 1.6 min, and viscosity around 31 and 2100 mPa s at 20 °C and 37 °C, respectively. NPs-in-thermo presented osmolality and pH values deemed compatible with the colorectal compartment, as well as reduced toxicity to the Caco-2 colorectal cell line. The composite system was also used to incorporate the anti-HIV microbicide model drug dapivirine.
In vitro
studies showed that dapivirine-loaded NPs-in-thermo was able to provide overall faster drug release as compared to dapivirine directly dispersed into phosphate buffered saline or the thermosensitive enema base. Finally, NPs-in-thermo was tested for distribution and retention in a mouse model by
in vivo
and
ex vivo
near infrared imaging. Qualitative and semi-quantitative data indicated that NPs exhibited slower but overall wider distribution and enhanced retention in the distal colon of mice treated intrarectally with NPs-in-thermo, namely when compared to NPs dispersed in liquid phosphate buffered saline. Overall, our data support that thermosensitive enemas may provide suitable platforms for the rectal administration of polymeric NPs, namely in the context of drug delivery.
The incorporation of nanoparticles into a thermosensitive enema enhances colorectal distribution and retention.
Brewer’s spent yeast (BSY) autolysates may have potential applications as food ingredients or nutraceuticals due to their antioxidant and ACE-inhibitory activities. The impact of simulated ...gastrointestinal (GI) digestion, the interaction with intracellular sources of oxidative stress, the intestinal cell permeability of BSY peptides, and the antioxidant and ACE-inhibitory activities of BSY permeates were assayed. Gastrointestinal digestion of BSY autolysates enhanced antioxidant and ACE-inhibitory activities as measured in vitro. No cytotoxic effects were observed on Caco-2 cells after exposure to the digested BSY autolysates within a concentration range of 0.5 to 3.0 mg of peptides/mL. A protective role to induced oxidative stress was observed. The transepithelial transport assays indicate high apparent permeability coefficient (P app) values for BSY peptides across Caco-2/HT29-MTX cell monolayer (14.5–26.1 × 10–6 cm/s) and for Caco-2 cell monolayer model (12.4–20.8 × 10–6 cm/s), while the antioxidant and ACE-inhibitory activities found in flux material from the basolateral side suggest transepithelial absorption of bioactive compounds.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Nanocarriers may provide interesting delivery platforms for microbicide drugs and their characterization should be addressed early in development. Differently surface-engineered dapivirine-loaded, ...poly(epsilon-caprolactone) (PCL)-based nanoparticles (NPs) were obtained by nanoprecipitation using polyethylene oxide (PEO), sodium lauryl sulfate (SLS), or cetyltrimethylammonium bromide (CTAB) as surface modifiers. Physical–chemical properties of NP aqueous dispersions were evaluated upon storage at −20–40°C for one year. NPs presented 170–200nm in diameter, roundish-shape, low polydispersity index (≤0.18), and high drug association efficiency (≥97%) and loading (≥12.7%). NPs differed in zeta potential, depending on surface modifier (PEO: −27.9mV; SLS: −54.7mV; CTAB: +42.4mV). No interactions among formulation components were detected by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), except for SLS–PCL NPs. Colloidal properties of NPs were lost at −20°C storage. Negatively charged NPs were stable up to one year at 5–40°C; as for CTAB–PCL NPs, particle aggregation was observed from 30 to 90 days of storage depending on temperature. Colloidal instability affected the in vitro drug release of CTAB–PCL NPs after 360 days. In any case, no degradation of dapivirine was apparent. Overall, PEO–PCL and SLS–PCL NPs presented suitable properties as nanocarriers for dapivirine. Conversely, CTAB–PCL NPs require additional strategies in order to increase stability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
An evaluation was made of the effect of anthelmintic treatments on the performance of Simmental X Nellore crossbred calves before and after weaning. To this end, the calves were divided into three ...groups: (1) treated monthly with a low efficacy anthelmintic drug, ivermectin; (2) treated monthly with a highly effective anthelmintic drug, albendazole; and (3) untreated control group. All the groups in this experiment showed an average fecal egg count of less than 400 eggs per gram (EPG), and no clinical signs of parasitic gastroenteritis. The blood variables were within the normal range and no calf presented anemia. In most of the samplings, mean EPGs were significantly lower (P<0.05) in the group treated with albendazole. The calves received dietary supplementation before and after weaning, which enabled them to gain weight in every month of the experiment and reach a body weight of about 250 kg on the last sampling date, before turning one year old. The anthelmintic treatments did not affect body weight gain, leading to the conclusion that, when fed with suitable dietary supplements, Simmental X Nellore crossbred calves are not affected by gastrointestinal nematode parasites acquired by grazing.
Recent developments in materials science and specific surface functionalization of materials are providing new tools for the rational design of precisely engineered drug delivery systems. Particular ...interest has been paid to the exploitation of functionalized materials in the administration of biopharmaceuticals by the oral route, traditionally challenging and frequently compromised when using conventional pharmaceutical approaches. Using such materials for producing particulate systems is a common approach to obtain advanced drug delivery systems capable of providing stable and biocompatible environments and allowing for a targeted delivery of the associated biopharmaceuticals. This work intends to provide a thorough, up-to-date and holistic discussion on specific engineering and surface functionalization strategies of multistage platforms towards the development of novel delivery platforms for oral drug administration, with particular focus on the different materials and their interactions at the biological-material-host interface. This review will also address the safety and toxicity concerns of the resulting drug delivery systems, as well as their regulatory status and pathway towards the market approval of novel biopharmaceutical products based on particulate delivery systems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were ...a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life, and poor penetration into HIV reservoir sites, which contribute to the suboptimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review is focused on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARV to overcome biological barriers upon administration. Furthermore, a correlation between these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference (RNAi) delivery for the treatment of HIV infections were also discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Resistance to ivermectin was detected in all herds evaluated.•Efficacy estimated from pre- and post-treatment egg counts in the same group presented smaller confidence intervals.•The faecal egg ...count reduction confidence intervals were usually wider when based on data obtained using the McMaster method than when data were obtained using the FLOTAC method.
The occurrence of anthelmintic resistance to levamisole, albendazole, ivermectin and moxidectin was investigated in cattle from 10 farms located in São Paulo State, Brazil, using two techniques for counting eggs in faeces: McMaster with a sensitivity of 50 eggs per gram (EPG) and FLOTAC with a sensitivity of two EPG. We also evaluated the use of different mathematical and test design approaches to determine the efficacy of the anthelmintic treatments: one formula/design that compares post-treatment arithmetic mean EPG counts for the treated and control groups (FECRT1) and two methods to analyse data from pre- and post-treatment EPG counts in the same group (FECRT2 and FECRT3, respectively). Treatment groups received either ivermectin (0.2mg/kg of body weight (BW); moxidectin (0.2mg/kg BW); albendazole (2.5mg/kg BW); levamisole (4.7mg/kg BW); or no treatment (control group). The number of animals in each group ranged from 8 to 11. Faecal samples from each animal were collected 2 days before the treatment and again 10 and 28 days post-treatment. The FEC reduction (FECR) confidence intervals were usually wider when based on data obtained using the McMaster method than when data were obtained using the FLOTAC method. Efficacy estimated from pre- and post-treatment EPG counts in the same group presented smaller confidence intervals. Ivermectin proved to be totally ineffective in all herds evaluated. Cooperia spp. was the major parasite displaying resistance, followed by Haemonchus spp. The results also indicated the presence of Oesophagostomum spp. and Trichostrongylus spp., meaning they, too, were resistant to ivermectin. Resistance to moxidectin was found on nine of the 10 farms investigated; however, only three farms had previously used moxidectin. In contrast, albendazole and levamisole demonstrated high efficacy on the majority of farms. In surveys for anthelmintic resistance in cattle, the use of a diagnostic method with higher sensitivity to detect eggs is recommended, as is the case with the FLOTAC method. This study indicates that by using techniques with high sensitivity and by testing the same animals pre- and post-treatment, good precision can be achieved with group sizes from 8 to 11 animals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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