Geographical distribution of Ixodes persulcatus and associated pathogens: Analysis of integrated data from a China field survey and global published data.

The increasing incidence and range expansion of tick-borne diseases have caused global threats to human and animal health under the background of climate and socioeconomic changes. As an efficient vector in transmission of tick-borne diseases, a growing burden caused by Ixodes persulcatus and associated pathogens could not be underestimated. This study summarized the distribution, hosts, and pathogens of I. persulcatus, and predicted the suitable habitats of this tick species worldwide. An integrated database involving a field survey, reference book, literature review, and related website was constructed. Location records of I. persulcatus and associated pathogens were incorporated into distribution maps using ArcGIS software. Positive rates for I. persulcatus-associated agents were estimated by meta-analysis. The global distribution of the tick species was predicted using Maxent model. I. persulcatus was distributed in 14 countries across the Eurasian continent, involving Russia, China, Japan, and several Baltic Sea states, which ranged between 21°N to 66°N. The tick species fed on 46 species of hosts, and 51 tick-borne agents could be harbored by I. persulcatus. The predictive model showed that I. persulcatus could be predominantly distributed in northern Europe, western Russia, and northern China. Our study fully clarified the potential public health risks posed by I. persulcatus and I. persulcatus-borne pathogens. Surveillance and control measures of tick-borne diseases should be enhanced to promote the health of humans, animals, and ecosystems.

New insights into the impact of microbiome on horizontal and vertical transmission of a tick-borne pathogen.

BACKGROUND: The impact of host skin microbiome on horizontal transmission of tick-borne pathogens , and of pathogen associated transstadial and transovarial changes in tick microbiome are largely unknown, but are important to control increasingly emerging tick-borne diseases worldwide. METHODS: Focusing on a rickettsiosis pathogen, Rickettsia raoultii, we used R. raoultii-positive and R. raoultii-negative Dermacentor spp. tick colonies to study the involvement of skin microbiota in cutaneous infection with rickettsiae in laboratory mice, and the function of the tick microbiome on maintenance of rickettsiae through all tick developmental stages (eggs, larvae, nymphs, adults) over two generations. RESULTS: We observed changes in the skin bacteria community, such as Chlamydia, not only associated with rickettsial colonization but also with tick feeding on skin. The diversity of skin microbiome differed between paired tick-bitten and un-bitten sites. For vertical transmission, significant differences in the tick microbiota between pathogenic rickettsia-positive and -negative tick chorts was observed across all developmental stages at least over two generations, which appeared to be a common pattern not only for R. raoultii but also for another pathogenic species, Candidatus Rickettsia tarasevichiae. More importantly, bacterial differences were complemented by functional shifts primed for genetic information processing during blood feeding. Specifically, the differences in tick microbiome gene repertoire between pathogenic Rickettsia-positive and -negative progenies were enriched in pathways associated with metabolism and hormone signals during vertical transmission. CONCLUSIONS: We demonstrate that host skin microbiome might be a new factor determining the transmission of rickettsial pathogens through ticks. While pathogenic rickettsiae infect vertebrate hosts during blood-feeding by the tick, they may also manipulate the maturation of the tick through changing the functional potential of its microbiota over the tick's life stages. The findings here might spur the development of new-generation control methods for ticks and tick-borne pathogens. Video Abstract.

Microplastics extraction from wastewater treatment plants: Two-step digestion pre-treatment and application.

As the gathering place of urban wastewater, wastewater treatment plants (WWTPs) are indispensable for removing microplastics (MPs), one of the emerging contaminants of great concern, from cities into the natural environment. A reliable and efficient extraction method for MPs, especially in organic-rich matrices, such as sludge samples, is the basis for studying MPs contamination, while it is still lacking. The digestion process, which requires further optimisation, is the most important step during extraction. In this study, we developed and optimised a two-step digestion process to extract MPs and proposed a recommended dosage of digestion reagents based on the mixed liquid volatile suspended solids (MLVSS) level of the sample. Successive addition of 30% H2O2 + 1 M HNO3 (v:v = 1:1, T = 60 °C, t = 5 h + 5 h) could efficiently extract MPs from sludge samples (over 90%), and the recommended dosage of digestion reagent was 100 ml 30% H2O2+100 ml 1 M HNO3 with the sample MLVSS lower than approximately 0.43 g. This new method was also applied to examine the characteristics of MPs in two typical WWTPs (anaerobic-anoxic-oxic and biofilter processes) in Shenzhen. The concentrations of MPs in the influent, effluent and dewatered sludge were approximately 114.00 n/L, 6.00 n/L, and 126.00 n/g (dry weight) in WWTP A, whereas 404.00 n/L, 22.00 n/L, and 204.00 n/g (dry weight) in WWTP B, respectively. Rayon and polyester were the dominant polymers in both the WWTPs. Fibers accounted for the largest proportion of the influent and effluent. Sizes between 0.20-0.50 mm were most detected. This study provides a new and efficient reference method to extract MPs from WWTPs samples, especially sludge sample, with less MPs loss and more beneficial to subsequent identification.

Metavirome of 31 tick species provides a compendium of 1,801 RNA virus genomes.

The increasing prevalence and expanding distribution of tick-borne viruses globally have raised health concerns, but the full repertoire of the tick virome has not been assessed. We sequenced the meta-transcriptomes of 31 different tick species in the Ixodidae and Argasidae families from across mainland China, and identified 724 RNA viruses with distinctive virome compositions among genera. A total of 1,801 assembled and complete or nearly complete viral genomes revealed an extensive diversity of genome architectures of tick-associated viruses, highlighting ticks as a reservoir of RNA viruses. We examined the phylogenies of different virus families to investigate virome evolution and found that the most diverse tick-associated viruses are positive-strand RNA virus families that demonstrate more ancient divergence than other arboviruses. Tick-specific viruses are often associated with only a few tick species, whereas virus clades that can infect vertebrates are found in a wider range of tick species. We hypothesize that tick viruses can exhibit both 'specialist' and 'generalist' evolutionary trends. We hope that our virome dataset will enable much-needed research on vertebrate-pathogenic tick-associated viruses.

Removing microplastics from aquatic environments: A critical review.

As one of the typical emerging contaminants, microplastics exist widely in the environment because of their small size and recalcitrance, which has caused various ecological problems. This paper summarizes current adsorption and removal technologies of microplastics in typical aquatic environments, including natural freshwater, marine, drinking water treatment plants (DWTPs), and wastewater treatment plants (WWTPs), and includes abiotic and biotic degradation technologies as one of the removal technologies. Recently, numerous studies have shown that enrichment technologies have been widely used to remove microplastics in natural freshwater environments, DWTPs, and WWTPs. Efficient removal of microplastics via WWTPs is critical to reduce the release to the natural environment as a key connection point to prevent the transfer of microplastics from society to natural water systems. Photocatalytic technology has outstanding pre-degradation effects on microplastics, and the isolated microbial strains or enriched communities can degrade up to 50% or more of pre-processed microplastics. Thus, more research focusing on microplastic degradation could be carried out by combining physical and chemical pretreatment with subsequent microbial biodegradation. In addition, the current recovery technologies of microplastics are introduced in this review. This is incredibly challenging because of the small size and dispersibility of microplastics, and the related technologies still need further development. This paper will provide theoretical support and advice for preventing and controlling the ecological risks mediated by microplastics in the aquatic environment and share recommendations for future research on the removal and recovery of microplastics in various aquatic environments, including natural aquatic environments, DWTPs, and WWTPs.

Coinfection of Two Rickettsia Species in a Single Tick Species Provides New Insight into Rickettsia-Rickettsia and Rickettsia-Vector Interactions.

Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses. There is an ongoing debate as to whether established infections by one Rickettsia species preclude the maintenance of the second species in ticks. Here, we identified two Rickettsia species in inoculum from Haemaphysalis montgomeryi ticks and subsequently obtained pure isolates of each species by plaque selection. The two isolates were classified as a transitional group and spotted fever group rickettsiae and named Rickettsia hoogstraalii str CS and Rickettsia rhipicephalii str EH, respectively. The coinfection of these two Rickettsia species was detected in 25.6% of individual field-collected H. montgomeryi. In cell culture infection models, R. hoogstraalii str CS overwhelmed R. rhipicephalii str EH with more obvious cytopathic effects, faster plaque formation, and increased cellular growth when cocultured, and R. hoogstraalii str CS seemed to polymerize actin tails differently from R. rhipicephalii str EH in vitro. This work provides a model to investigate the mechanisms of both Rickettsia-Rickettsia and Rickettsia-vector interactions. IMPORTANCE The rickettsiae are a group of obligate intracellular Gram-negative bacteria that include human pathogens causing an array of clinical symptoms and even death. There is an important question in the field, that is whether one infection can block the superinfection of other rickettsiae. This work demonstrated the coinfection of two Rickettsia species in individual ticks and further highlighted that testing the rickettsial competitive exclusion hypothesis will undoubtedly be a promising area as methods for bioengineering and pathogen biocontrol become amenable for rickettsiae.

Trafficked Malayan pangolins contain viral pathogens of humans.

Pangolins are the most trafficked wild animal in the world according to the World Wildlife Fund. The discovery of SARS-CoV-2-related coronaviruses in Malayan pangolins has piqued interest in the viromes of these wild, scaly-skinned mammals. We sequenced the viromes of 161 pangolins that were smuggled into China and assembled 28 vertebrate-associated viruses, 21 of which have not been previously reported in vertebrates. We named 16 members of Hunnivirus, Pestivirus and Copiparvovirus pangolin-associated viruses. We report that the L-protein has been lost from all hunniviruses identified in pangolins. Sequences of four human-associated viruses were detected in pangolin viromes, including respiratory syncytial virus, Orthopneumovirus, Rotavirus A and Mammalian orthoreovirus. The genomic sequences of five mammal-associated and three tick-associated viruses were also present. Notably, a coronavirus related to HKU4-CoV, which was originally found in bats, was identified. The presence of these viruses in smuggled pangolins identifies these mammals as a potential source of emergent pathogenic viruses.

Natural infection of pangolins with human respiratory syncytial viruses.

Respiratory syncytial virus (RSV) is an enveloped non-segmented negative sense RNA virus that belongs to Orthopneumovirus genus of the Pneumoviridae family in the order Mononegavirales. The virus is the leading cause of severe respiratory disease in children under two years of age and is responsible for substantial disease burden in infants and elder people in both developed and developing countries1,2. RSV is only known to circulate among humans, though it was first isolated from chimpanzees3. The virus can experimentally infect mice, rats, cotton rats, ferrets, and hamsters, but does not naturally circulate in these animal populations4. We found that Malayan pangolins (Manis javanica) were naturally infected with RSVs that have 99.4-99.8% genomic identity with strains circulating in humans. Phylogenetic analyses revealed that five RSVs in pangolins were RSV-A ON1 and seven were RSV-B BA genotypes, both of which are currently prevalent in humans worldwide. These findings suggest that humans might transmit their viruses to endangered wildlife.

The contamination of microplastics in China's aquatic environment: Occurrence, detection and implications for ecological risk.

The widespread occurrence of microplastics in aquatic ecosystems that resulted in environmental contamination has attracted worldwide attention. Microplastics pose a potential threat to the growth and health of aquatic organisms, thereby affecting the function of the ecosystems. As one of the top ten countries producing and consuming plastic products globally, China's aquatic ecosystems have been profoundly affected by microplastics. In this review, we have summarized the microplastics contamination in three typical water environments (marine environment, freshwater environment, and wastewater treatment plants) in China, elaborated on the adverse impacts of microplastics on the ecological environment, and evaluated the potential ecological risks exposed to the ecosystem. In addition, the progress of microplastics extraction methods, as the important basis of microplastics related research, in aquatic ecosystems was introduced, especially the difference between the extraction of microplastics from wastewater and sludge samples. At present, most of the research on microplastics focuses on "one point", such as a certain river or wastewater treatment plant. Research on the mitigation and transfer of microplastics among different connected water environments is still lacking. Also, the microscale ecotoxicity caused by microplastics is poorly understood. In the end, we proposed suggestions and perspectives for future research regarding microplastics in the aquatic ecosystems in China.

Distribution of Dermacentor silvarum and Associated Pathogens: Meta-Analysis of Global Published Data and a Field Survey in China.

Dermacentor silvarum is an obligate blood sucking arthropod and transmits various pathogens to humans and domestic animals. Recently several new viruses were detected in D. silvarum as an emerging disease threat. In this study, we aimed to analyze its geographical distribution and associated pathogens. Data were collected from multiple sources, including a field survey, reference book, and literature review. We searched various electronic databases with the terms "Dermacentor silvarum" OR "D. silvarum" for studies published since 1963 and the positive rates for Dermacentor silvarum-associated pathogens were estimated by meta-analysis. D. silvarum was found only in four countries in Eurasia, ranging from 22° N to 57° N latitude. At least 20 human pathogens were associated with D. silvarum, including five species of spotted fever group rickettsiae, three species in the family of Anaplasmataceae, three genospecies in the complex Borrelia burgdorferi sensu lato, Francisella tularensis, Babesia venatorum, Coxiella buenetii, Borrelia miyamotoi, and five species of virus. Among them, Rickettsia raoultii was widely detected in D. silvarum, showing the highest pooled positive rate (25.15%; 95% CI 13.31-39.27). Our work presents the most comprehensive data and analysis (to our knowledge) for the geographical distribution of D. silvarum and associated pathogens, revealing an emerging threat to public health and stocking farming. Continued surveillance and further investigations should be enhanced.

Detection of Novel Spotted Fever Group Rickettsiae (Rickettsiales: Rickettsiaceae) in Ticks (Acari: Ixodidae) in Southwestern China.

Spotted fever group rickettsiae, mainly maintained and transmitted by ticks, are important etiological agents of (re)emerging zoonotic diseases worldwide. It is of great significance to investigate spotted fever group rickettsiae in ticks in different areas for the prevention and control of rickettsioses. In this study, a total of 305 ticks were collected from wild and domestic animals in Chongqing, Guizhou, Yunnan, and Guangxi provinces of southwestern China during 2017-2019 and examined for the presence of spotted fever group rickettsiae by PCR with primers targeting the partial gltA, ompA, rrs, and htrA genes. Results showed that two spotted fever group rickettsiae species, including the pathogenic Candidatus Rickettsia jingxinensis (Rickettsiales: Rickettsiaceae) and a potential novel species Rickettsia sp. sw (Rickettsiales: Rickettsiaceae), were identified. The Ca. R. jingxinensis sequences were recovered from Rhipicephalus microplus (Ixodida: Ixodidae) and Haemaphysalis longicornis (Ixodida: Ixodidae) ticks and phylogenetically clustered with previous Ca. R. jingxinensis, Ca. R. longicornii (Rickettsiales: Rickettsiaceae), and Rickettsia sp. XY118 (Rickettsiales: Rickettsiaceae) strains. Rickettsia sp. sw was detected in Amblyomma geoemydae (Ixodida: Ixodidae) and Rh. microplus. Interestingly, as far as we know, this was the first report of Rickettsia (Rickettsiales: Rickettsiaceae) in A. geoemydae. Phylogenetic analyses indicated that this potential novel species was closely related to R. aeschlimannii (Rickettsiales: Rickettsiaceae) with gltA and ompA genes and grouped in a cluster composed of R. montanensis (Rickettsiales: Rickettsiaceae), R. raoultii (Rickettsiales: Rickettsiaceae), R. aeschlimannii, R. massiliae (Rickettsiales: Rickettsiaceae), and R. rhipicephali (Rickettsiales: Rickettsiaceae) with htrA, while formed a separate clade with rrs. The pathogenicity of Rickettsia sp. sw should be further confirmed. These results expand the knowledge of the geographical distribution and vector distribution of spotted fever group rickettsiae in China and are useful for assessing the potential public health risk.

Prevalence of Multiple Tick-Borne Pathogens in Various Tick Vectors in Northeastern China.

Background: Tick-borne bacteria and protozoa can cause a variety of human and animal diseases in China. It is of great importance to monitor the prevalence and dynamic variation of these pathogens in ticks in ever-changing natural and social environment. Materials and Methods: Ticks were collected from Heilongjiang and Jilin provinces of northeastern China during 2018-2019 followed by morphological identification. The presence of Rickettsia spp., Anaplasma spp., Ehrlichia spp., Borrelia spp., Babesia spp., and Theileria spp. was examined by PCR and Sanger sequencing. The obtained sequences were subjected to phylogenetic analysis through Mega 7.0. Statistical analysis was performed using SPSS 24.0. Results: A total of 250 ticks from 5 species of 3 genera were collected. Ixodes and Haemaphysalis ticks carried more species of pathogens than Dermacentor, and the pathogens detected in Haemaphysalis japonica varied significantly among different sampling sites. The infection rates of Rickettsia spp., Anaplasma spp., Ehrlichia spp., Borrelia spp., Babesia spp., and Theileria spp. were 41.2%, 0, 2.0%, 7.2%, 1.2%, and 7.2%, respectively. Twelve pathogens were identified, among which Rickettsia raoultii (29.6%), Candidatus Rickettsia tarasevichiae (9.2%), and Theileria equi (4.4%) were the three most common ones. Rickettsia had its dominant vector, that is, R. raoultii had high infection rates in Dermacentor nuttalli and Dermacentor silvarum, Ca. R. tarasevichiae in Ixodes persulcatus, and Rickettsia heilongjiangensis in H. japonica. Interestingly, unclassified species were observed, including a Rickettsia sp., an Ehrlichia sp., a Borrelia sp., and a Babesia sp. Coinfections with different pathogens were identified in 9.2% of all tested ticks, with I. persulcatus most likely to be coinfected (23.8%) and Rickettsia spp. and Borrelia spp. as the most common combination (16.7%). Conclusions: The results of this study reflect high diversity and complexity of pathogens in ticks, which are useful for designing more targeted and effective control measures for tick-borne diseases in China.

Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

Distribution of Haemaphysalis longicornis and associated pathogens: analysis of pooled data from a China field survey and global published data.

BACKGROUND: Haemaphysalis longicornis, a vector of various pathogens with medical and veterinary importance, is native to eastern Asia, and recently reached the USA as an emerging disease threat. In this study, we aimed to identify the geographical distribution, hosts, and associated pathogens of H longicornis. METHODS: Data were collected from multiple sources, including a field survey, reference book, literature review, and related websites. The thematic maps showing geographical distribution of H longicornis and associated pathogens were produced by ArcGIS. Hosts of H longicornis and positive rates for H longicornis-associated pathogens were estimated by meta-analysis. Ecological niche modelling was used to predict potential global distribution of H longicornis. FINDINGS: H longicornis was found to be present in ten countries, predominantly in eastern Asia, the USA, Australia, and New Zealand. The tick was known to feed on a variety of domestic and wild animals, and humans. At least 30 human pathogens were associated with H longicornis, including seven species of spotted fever group rickettsiae, seven species in the family of Anaplasmataceae, four genospecies in the complex Borrelia burgdorferi sensu lato, two Babesia species, six species of virus, and Francisella, Bartonella, Coxiella, and Toxoplasma, which were mainly reported in eastern Asia. The predictive modelling revealed that H longicornis might affect more extensive regions, including Europe, South America, and Africa, where the tick has never been recorded before. INTERPRETATION: H longicornis is relatively common in the world, and is associated with various human and animal pathogens. Authorities and health-care workers should be aware of the threat of the tick species to public health and veterinary medicine. Surveillance and further investigations should be enhanced globally. FUNDING: National Natural Science Foundation of China and National Key Research and Development Program of China.

Potentials of proniosomes for improving the oral bioavailability of poorly water-soluble drugs.

UNLABELLED: Abstract Objective: The objectives of this study were, first, to develop a free-flowing and stable proniosome formulation for poorly water-soluble drugs such as vinpocetine; and second, to estimate its bioavailability as oral drug delivery system. METHODS: The proniosomes consisting of span60, cholesterol, sorbitol and vinpocetine were prepared by a novel approach. After the proniosomes were contacted with water, the suspension of vinpocetine-loaded niosomes formed automatically. The proniosomes and reconstituted niosomes were evaluated for their physicochemical characteristics, in vitro drug dissolution and release, integrity and stability at different GI tract pH conditions, in situ single-pass intestinal perfusion and in vivo bioavailability. RESULTS: The proniosome powder exhibited excellent flowability. The reconstituted niosomes with high drug entrapment efficiency (89.67 ± 3.28%) showed spherical morphology with smooth surface under transmission electron microscope (TEM). X-ray diffraction (XRD) indicated that the drug was in an amorphous or molecular state in proniosome powder. In vitro dissolution and release study, proniosomes did enhance the dissolution and release rate compared to vinpocetine suspension in phosphate buffer solution (pH 7.2). Proniosome-derived niosomes could keep their integrity and stability at different GI tract pH conditions. The in situ single-pass intestinal perfusion indicated that encapsulation of vinpocetine into niosomes could largely improved the absorption of vinpocetine. The AUC(0-∞) of F2 and F3 was about 4.0- and 4.9-fold higher than that of the vinpocetine suspension, respectively. The results demonstrated the proniosomes indeed remarkably enhanced the oral bioavailability of vinpocetine. CONCLUSION: This study suggested the potential of proniosomes as stable precursors for the immediate preparation of niosome carrier systems.

In vitro and in vivo evaluations of a novel pulsed and controlled osmotic pump capsule.

OBJECTIVE: For better treatment of circadian cardiovascular events, a novel Propranolol hydrochloride (PNH) delayed-release osmotic pump capsule was developed. METHODS: The capsule body was designed of asymmetric membrane and the capsule cap was made impermeable. The physical characteristics of capsule body walls and membrane permeability were compared among different coating solutions. RESULTS: The formulation with the glycerin and diethyl phthalate (DEP) ratio of 5:4 appeared to be the best. The lag time and subsequent drug release were investigated through assembling the capsule body with capsule caps of different length. WSR N-10 was chosen as the suspending for its moderate expanding capacity. The influence of factors (WSR N-10 content, NaCl content and capsule cap length) on the responses (lag time and drug release rate) was evaluated using central composite design-response surface methodology. A second-order polynomial equation was fitted to the data and actual response values were in good accordance with the predicted ones. The optimized formulation displayed complete drug delivery, zero-order release rate with 4-h lag time. The results of in vivo pharmacokinetics in beagle dogs clearly suggested the controlled and sustained release of PNH from the system and that the relative bioavailability of this preparation was about 1.023 comparing the marketed preparation. CONCLUSIONS: These results indicate that by the adjustment of capsule cap length, PNH could be developed as a novel pulsatile and controlled drug delivery system.

Design and evaluation of a novel formulation prediction system.

PURPOSE: The purpose of this study is to design and evaluate a novel formulation prediction system for formulation study of monolithic osmotic pump tablets (MOPTs). METHODS: Ternary-component diagram was originally brought forward to evaluate MOPTs formulations. Optimal formulation regions were delimited in ternary-component diagrams. Water-insoluble drug gliclazide was chosen as a model drug for selecting most suitable suspending agent. With five model drugs, we obtained five ternary-component diagrams. By MATLAB(®) software, a triangular prism model was then established regarding doses as vertical coordinate and the five diagrams as cross-sections, with the formation of an optimal formulation channel in it, followed by the design of formulation prediction software (FPS 1.0). The practicality of the system was finally validated. RESULTS: After entering the drug information, we immediately obtained the optimal formulation region for preparing MOPTs with interpolation algorithm. The dissolution test results of the four randomly selected formulations all met the evaluating conditions. CONCLUSIONS: Ternary-component diagram is useful for MOPTs formulation optimization. The predictive ability of the system is tentatively confirmed and the experiment efficiency is greatly improved.

Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability.

The purpose of this study is to develop an optimized nanostructured lipid carriers (NLC) formulation for vinpocetine (VIN), and to estimate the potential of NLC as oral delivery system for poorly water-soluble drug. In this work, VIN-loaded NLC (VIN-NLC) was prepared by a high pressure homogenization method. The VIN-NLC showed spherical morphology with smooth surface under transmission electron microscope (TEM) and scanning electron microscopic (SEM) analysis. The average encapsulation efficiency was 94.9+/-0.4%. The crystallization of drug in NLC was investigated by powder X-ray diffraction and differential scanning calorimetry (DSC). The drug was in an amorphous state in the NLC matrix. In the in vitro release study, VIN-NLC showed a sustained release profile of VIN and no obviously burst release was observed. The oral bioavailability study of VIN was carried out using Wistar rats. The relative bioavailability of VIN-NLC was 322% compared with VIN suspension. In conclusion, the NLC formulation remarkably improved the oral bioavailability of VIN and demonstrated a promising perspective for oral delivery of poorly water-soluble drugs.

A novel gastro-retentive osmotic pump capsule using asymmetric membrane technology: in vitro and in vivo evaluation.

PURPOSE: The purpose of this paper is to develop a novel gastro-retentive osmotic pump capsule using asymmetric membrane technology. METHODS: The physical characteristics of capsule walls and drug delivery behaviors of the system were compared through different coating solutions. The formulation with the glycerin and diethyl phthalate ratio of 5:4 appears to be the best. The thickness of asymmetric membranes was evaluated by withdrawing speed. The relation between the two can be fitted to a linear model. The floating abilities were investigated through filling polyethylene oxide of different molecular weight into the capsules. WSR N-80 (molecular weight 200000) is chosen for the longest floating time. Central composite design-response surface methodology was used to investigate the influence of factors on the responses. The in vivo pharmacokinetics were studied in beagle dogs. RESULTS AND CONCLUSIONS: A second-order polynomial equation was fitted to the data, and the actual response values are in good accordance with the predicted ones. The optimized formulation displays a complete drug delivery, zero-order release rate and 12 h floating time. The in vivo study results clearly indicate the controlled and sustained release of Famotidine from the system, and the relative bioavailability of this preparation is about 1.605 in comparison to that of the marketed preparation.