Safety, immunogenicity and efficacy of an mRNA-based COVID-19 vaccine, GLB-COV2-043, in preclinical animal models.

Several COVID-19 vaccines, some more efficacious than others, are now available and deployed, including multiple mRNA- and viral vector-based vaccines. With the focus on creating cost-effective solutions that can reach the low- and medium- income world, GreenLight Biosciences has developed an mRNA vaccine candidate, GLB-COV2-043, encoding for the full-length SARS-CoV-2 Wuhan wild-type spike protein. In pre-clinical studies in mice, GLB-COV2-043 induced robust antigen-specific binding and virus-neutralizing antibody responses targeting homologous and heterologous SARS-CoV-2 variants and a TH1-biased immune response. Boosting mice with monovalent or bivalent mRNA-LNPs provided rapid recall and long-lasting neutralizing antibody titers, an increase in antibody avidity and breadth that was held over time and generation of antigen-specific memory B- and T- cells. In hamsters, vaccination with GLB-COV2-043 led to lower viral loads, reduced incidence of SARS-CoV-2-related microscopic findings in lungs, and protection against weight loss after heterologous challenge with Omicron BA.1 live virus. Altogether, these data indicate that GLB-COV2-043 mRNA-LNP vaccine candidate elicits robust protective humoral and cellular immune responses and establishes our mRNA-LNP platform for subsequent clinical evaluations.

Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters.

Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases.

Which social media platforms matter and for whom? Examining moderators of links between adolescents' social media use and depressive symptoms.

INTRODUCTION: Despite extensive research on social media and risks for mental health, not enough is known about individual differences in these risks. METHODS: The present study, with data collected from 2018 to 2020, investigated the association between social media use (total and for specific platforms) and depressive symptoms in a sample of 237 American adolescents (Mage = 15.10; SD = 0.49; 51.1% girls and 48.5% boys). We investigated several moderators: gender, self-esteem, personality, and negative reactions to social media. Covariates were gender, timing of the follow-up (pre vs. during the pandemic), and depressive symptoms a year earlier. RESULTS: Results indicated that greater total time spent on social media was associated with higher levels of depressive symptoms. This effect held for Instagram, TikTok, and YouTube (but not Snapchat, Facebook, or Twitter). Several moderated effects were found. Twitter was associated with more depressive symptoms for girls but not boys. More frequent Instagram use was linked to more depressive symptoms for less or average-level extraverted teens but not for more extraverted teens, suggesting extraversion may be protective. More frequent TikTok use was associated with more depressive symptoms, particularly for teens who said they have more or average-level negative reactions to social media a year earlier. CONCLUSIONS: This study suggests that certain adolescents may be at increased risk for serious mental health challenges, like elevated depressive symptoms, when using TikTok, Instagram, or Twitter more frequently, underscoring the importance of examining individual differences and particular social media platforms.

Technology-guided assessment of vocalisations and their diagnostic value as pain indicators for people living with dementia.

BACKGROUND: during pain assessment in persons unable to self-report, such as people living with dementia, vocalisations are commonly used as pain indicators. However, there is a lack of evidence from clinical practice regarding their diagnostic value and relationship with pain. We aimed to explore vocalisations and pain in people with dementia undergoing pain assessments in clinical practice settings. METHODS: a total of 22,194 pain assessments were reviewed in people with dementia (n = 3,144) from 34 different Australian aged care homes and two dementia specific programs. Pain assessments were conducted by 389 purposely trained health care professionals and cares using PainChek pain assessment tool. Vocalised expressions were determined based on nine vocalisation features included in the tool. Linear mixed models were used to examine the relationship of pain scores with vocalisation features. Using a single pain assessment for each of the 3,144 people with dementia, additional data analysis was conducted via Receiver Operator Characteristic (ROC) analysis and Principal Component Analysis. RESULTS: vocalisation scores increased with increasing pain intensity. High pain scores were more likely with the presence of sighing and screaming (8 times). The presence of vocalisation features varied depending on the intensity of pain. The ROC optimal criterion for the voice domain yielded a cut-off score of ≥2.0 with a Youden index of 0.637. The corresponding sensitivity and specificity were 79.7% [confidence interval (CI): 76.8-82.4%] and 84.0% (CI: 82.5-85.5%), respectively. CONCLUSION: we describe vocalisation features during presence of different levels of pain in people with dementia unable to self-report, therefore providing evidence in regard to their diagnostic value in clinical practice.

Uptake of selected antiretrovirals by pepper (Capsicum annum), radish (Raphanus sativus), and ryegrass (Lolium perenne) grown on two contrasting soils and fertilized with human urine-derived fertilizers.

The use of urine-derived fertilizers has several economic and environmental advantages. However, there is concern that pharmaceutical residues present in urine could enter the food chain after plant uptake and pose potential risks to human and animal health. A pot experiment was conducted to evaluate the uptake of nine target antiretroviral drugs (ARVDs) by pepper (Capsicum annum), ryegrass (Lolium perenne) and radish (Raphanus sativus) grown in two soils of contrasting texture and organic matter content and fertilized with stored urine, nitrified urine concentrate (NUC), and struvite. Nevirapine was the only ARVD detected in crops grown with NUC and struvite on both soils, but the concentrations were below the limit of quantification. Plants fertilized with stored urine absorbed lamivudine, ritonavir, stavudine, emtricitabine, nevirapine, and didanosine, while abacavir, efavirenz and zidovudine were not detected. The ARVDs detected in the soils after harvest were significantly higher in the soil with high organic matter and clay content. To assess direct human exposure the estimated daily dietary intake (DDI) of ARVDs by consumption of the pepper and radish fertilized with stored urine was compared with the Threshold of Toxicological Concern (TTC) values based on the Cramer classification tree. The calculated DDI values for all ARVDs were about 300-3000 times lower than the TTC values for class III compounds. Therefore, daily consumption of these crops fertilized with stored urine does not pose a health risk to the consumer. Future research is required to assess the impact of ARVD metabolites, which may be more harmful to human health than the parent compounds.

Total organic carbon, aluminium and iron in bulk samples and aggregate size fractions of a sandy clay loam humic soil under sugarcane relative to native forest in northern KwaZulu-Natal, South Africa.

The distribution of total aluminium (Al) and iron (Fe) and organic carbon (TOC) in aggregate fractions gives an insight into the dynamics of these elements in soil. This study determined the effects of over 30 years of sugarcane cultivation, compared to adjacent native forest, on Al, Fe and TOC in bulk soil and aggregate fractions within the 100 cm depth of a sandy clay loam humic soil. Samples were separated into large macro-aggregates: LM (>2000 µm), small macro-aggregates: SM (250-2000 µm), micro-aggregates: M (250-63 µm) and silt + clay: SC (<63 µm) fractions. The TOC was analyzed by dry combustion and total Al and Fe by X-ray fluorescence spectrometry. Sugarcane cultivation (i) reduced macro-aggregates and TOC and (ii) increased the SC fraction and total Al and Fe. The mean weight diameter declined from 1.32 mm (0-30 cm) to 1.06 mm (30-100 cm) under forest. Average (0-100 cm) Al and Fe contents (g kg-1) increased in LM (6-16 for Al; 6 to 9 for Fe), SM (7-11 for Al), M (5-14 for Al; 6 to 9 for Fe) and SC (7-16 for Al; 9 to 10 for Fe) under sugarcane relative to forest. The TOC (g kg-1) declined in the LM (13-7) and SM (7-6) but increased in the M (5-9) and SC (10-13) due to cultivation. These findings suggested that sugarcane cultivation decreases aggregate stability and TOC in macro-aggregates, and increases Al and Fe in all aggregates. Adoption of practices inclined to improve or maintain TOC as well as liming to increase pH are necessary management practices for sustainable production.

A Novel Piggyback Strategy for mRNA Delivery Exploiting Adenovirus Entry Biology.

Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. Nonetheless, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied "piggyback" transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an effective pathway for transport of mRNA to the cellular cytosol for transgene expression. Our studies confirmed that AdpL could mediate effective gene transfer of mRNA vectors in vitro and in vivo. Facets of this method may offer key utilities to actualize the promise of mRNA-based therapeutics.

Land use and site effects on the distribution of carbon in some humic soil profiles of KwaZulu-Natal, South Africa.

Land use effects on the stocks of soil organic carbon (SOC) are generally based on the topsoil. Although subsoil horizons have lower concentrations, they contain a significant amount of SOC which may be more strongly protected than that in the topsoil layers. Analysis of SOC storage must therefore include the whole profile in respect of climate change mitigation. Humic soils in South Africa have high organic C in the A horizon, while the amount of C stocks through the whole profile depth is unknown. This study was conducted at six sites in KwaZulu-Natal Province to determine the effect of land use and site factors on C stocks, texture, pH and extractable aluminium (Al) and iron (Fe) concentrations and their vertical distribution to 100 cm in soils with thick (>45 cm) and thin (<45 cm) humic A horizons. The land use at some sites had been changed from grassland to maize and cultivated pasture and at others from forest to sugarcane farming. Cultivation with field crops reduced the organic C, mainly in the upper 20 cm (from 110 to 22 g C kg-1), with limited effect in deeper layers. The soils with thick humic A horizons and coarser texture stored more C in the deeper layers compared to those with thin humic A horizons and finer texture which had more of the C stocks in the 0-20 cm depth. Although cultivation reduced the soil C stocks in the surface layers, land use did not significantly affect the overall C stock (0-100 cm) at all sites. The high contents of extractable Fe (up to 340 mg kg-1) and Al (up to 3700 mg kg-1) stabilised the soil C and were more important than the effects of either land use or other site factors.

Risk and Protective Factors for Changes in Adolescent Psychosocial Adjustment During COVID-19.

The current study examined (1) changes in psychosocial adjustment among adolescents completing two surveys before COVID-19 and those completing the final survey during COVID-19 and (2) related risk/protective factors. Participants were 208 US adolescents (Mage  = 15.09, SD = 0.50, 48.8% female, 86.1% White; 40.9% COVID group) who completed longitudinal surveys assessing psychosocial adjustment and related risk/protective factors (e.g., emotion regulation, well-being pursuits). Only adolescents completing Wave 3 during COVID-19 experienced increases in depressive symptoms, negative affect, and isolation and decreases in positive affect and friendship. Several variables served as risk (i.e., dampening) and protective (i.e., eudaimonic and hedonic motives) factors of these changes. Findings highlight the range of factors that are distinctly associated with negative changes in adolescent adjustment during COVID-19.

When Wanting the Best Goes Right or Wrong: Distinguishing Between Adaptive and Maladaptive Maximization.

Researchers have often disagreed on how to define maximization, leading to conflicting conclusions about its potential benefits or drawbacks. Drawing from motivation research, we distinguish between the goals (i.e., wanting the best) and strategies (e.g., alternative search) associated with maximizing. Three studies illustrate how this differentiation offers insight into when maximizers do or do not experience affective costs when making decisions. In Study 1, we show that two motivational orientations, promotion focus and assessment mode, are both associated with the goal of wanting the best, yet assessment (not promotion) is related to the use of alternative search strategies. In Study 2, we demonstrate that alternative search strategies are associated with frustration on a discrete decision task. In Study 3, we provide evidence that one reason for this link may be due to reconsideration of previously dismissed options. We discuss the potential of this approach to integrate research in this area.

Divergent effects of distance versus velocity disturbances on emotional experiences during goal pursuit.

Disturbances are factors outside of a person's control that influence goal progress. Although disturbances are typically included in theoretical accounts of goal pursuit, relatively little empirical research has explicitly considered the effects of disturbances on the goal-striving process. We address this gap in the literature by examining the effects that disturbances have on the emotional experience of goal pursuit. More importantly, we differentiate between distance disturbances (changes to the amount of progress made) and velocity disturbances (changes to the rate of progress made). We conducted 2 experiments (N = 62 and N = 134) in which participants completed work simulation tasks to earn a $5.00 reward. Partway through the experiment participants' progress was inhibited by either a distance disturbance or a velocity disturbance. Importantly, the distance and velocity disturbances were equated in terms of their influence on the likelihood of obtaining the cash prize. In both studies the introduction of a disturbance decreased enthusiasm and increased frustration. However, over time the effects of distance and velocity disturbances on enthusiasm and frustration diverged. Specifically, the velocity disturbance had a more enduring effect on these emotions, relative to the distance disturbance. Downstream, in Study 1 enthusiasm positively predicted goal commitment. In Study 2 enthusiasm positively predicted goal commitment, effort, and task performance. Likewise, in Study 2 frustration negatively predicted goal commitment and task performance. Therefore, relative to distance disturbances, velocity disturbances appear to be more disruptive to goal pursuit. We discuss theoretical implications and practical implications for managing employee motivation. (PsycINFO Database Record

Tolerating the "doubting Thomas": how centrality of religious beliefs vs. practices influences prejudice against atheists.

Past research has found a robust effect of prejudice against atheists in largely Christian-dominated (belief-oriented) samples. We propose that religious centrality of beliefs vs. practices influences attitudes toward atheists, such that religious groups emphasizing beliefs perceive non-believers more negatively than believers, while groups emphasizing practices perceive non-practicing individuals more negatively than practicing individuals. Studies 1-2, in surveys of 41 countries, found that Muslims and Protestants (belief-oriented) had more negative attitudes toward atheists than did Jews and Hindus (practice-oriented). Study 3 experimentally manipulated a target individual's beliefs and practices. Protestants had more negative attitudes toward a non-believer (vs. a believer), whereas Jews had more negative attitudes toward a non-practicing individual (vs. a practicing individual, particularly when they had a Jewish background). This research has implications for the psychology of religion, anti-atheist prejudice, and cross-cultural attitudes regarding where dissent in beliefs or practices may be tolerated or censured within religious groups.

Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats.

Our objective is to develop a new therapy for the treatment of stroke. Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin (AAT), a serine proteinase inhibitor with potent anti-inflammatory, anti-apoptotic, antimicrobial, and cytoprotective activities, could be beneficial in stroke. The goal of this study is to test whether AAT can improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial (i.c.) microinjection of endothelin-1. Five to 10 minutes after stroke induction, rats received either i.c. or intravenous delivery of human AAT. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours, the infarct volumes of the human AAT treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (P < .0001 and P < .05, respectively) compared with control rats. Human AAT significantly limited sensory motor system deficits. Human AAT could be a potential novel therapeutic drug for the protection against neurodegeneration after ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models.

Utilizing community pharmacy dispensing records to disclose errors in hospital admission drug charts.

OBJECTIVE: To identify and resolve discrepancies in admission medication histories, utilizing community pharmacy dispensing data, in newly hospitalized patients and investigate the relationship between unresolved discrepancies and length of hospital stay. METHODS: Eligible patients (2 or more chronic conditions, 3 or more chronic medications and aged over 50 years) were randomized to the intervention or control group. Within 24 h of admission, the patient's nominated community pharmacy was contacted, a 6-month dispensing history obtained, patient was interviewed and a current medication list compiled. This was compared with the hospital drug chart. Discrepancies for the intervention group were discussed with the attending doctor. Subsequent resolution of discrepancies was assessed for all patients. RESULTS: 487 patients were included (203 intervention, 284 control). Approximately 66% of all patients had at least 1 discrepancy between their reconciled list of medications and their initial drug chart, with no significant difference between the groups. Significantly more intervention patients had at least 1 discrepancy resolved in the first 48 h than control patients (intervention 78.1%; control 36.5%; p < 0.0001). A weak correlation was found between the number of discrepancies not acted on and length of hospital stay (Spearman Rho = 0.1, n = 487, p < 0.01). CONCLUSION: Errors in admission medication histories are common and potentially lead to an increased length of stay. The provision of a 6-month community pharmacy dispensing history at the time of hospital admission is an important addition to ensure an accurate medication chart is compiled.

The protective effects of plasma gelsolin on stroke outcome in rats.

BACKGROUND: To date, recombinant tissue plasminogen activator (rtPA) is the only approved drug for ischemic stroke. It is intravenously administered functioning as a thrombolytic agent and is used to obtain reperfusion of the affected area of the brain. Excitotoxicity, inflammation and apoptosis are all involved in delayed neuronal death following stroke and offer multiple opportunities to intervene with neuroprotective agents. Gelsolin (GSN) is an actin- and calcium-binding protein mediating the disassembly of actin filaments and activity of calcium channels. It also functions as a regulator of apoptosis and inflammatory responses. This study tests the hypothesis that increasing the concentration of the form of GSN known as plasma GSN (pGSN) near an infarct will provide neuroprotection following ischemic stroke. METHODS: We induced middle cerebral artery occlusion (MCAO) in male rats via intracranial injection of endothelin-1 (ET-1), a potent vasoconstrictor, and then treated with local delivery of pGSN. Whole brain laser Doppler perfusion imaging was performed through the skull to assess MCAO effectiveness. Cylinder and vibrissae tests evaluated sensorimotor function before and 72 h after MCAO. Infarct volumes were examined 72 h after MCAO via 2, 3, 5-triphenyltetrazolium chloride (TTC) assay. RESULTS: Estimates of relative cerebral perfusion were significantly decreased in all groups receiving MCAO with no differences detected between treatments. Despite equivalent initial strokes, the infarct volume of the pGSN treatment group was significantly reduced compared with the untreated MCAO rats at 72 h. ET-1 induced significant deficits in both cylinder and vibrissae tests while pGSN significantly limited these deficits. CONCLUSION: Gelsolin could be a promising drug for protection against neurodegeneration following ischemic stroke.

Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions.

BACKGROUND: X linked intellectual disability (XLID) is common, with an estimated prevalence of 1/1000. The expanded use of array comparative genomic hybridisation (CGH) has led to the identification of several XLID-associated copy-number variants. METHODS: Array CGH analysis was performed using chromosomal microarray with ∼105 000 oligonucleotides covering the entire genome. Confirmatory fluorescence in situ hybridisation analyses were subsequently performed. Chromosome X-inactivation (XCI) was assessed using methylation-sensitive restriction enzyme digestion followed by PCR amplification. RESULTS: A novel ∼0.5 Mb duplication in Xq28 was identified in four cognitively impaired males who share behavioural abnormalities (hyperactivity and aggressiveness) and characteristic facial features (high forehead, upper eyelid fullness, broad nasal bridge and thick lower lip). These duplications were inherited from mothers with skewed XCI and are mediated by nonallelic homologous recombination between the low-copy repeat regions int22h-1 and int22h-2, which, in addition to int22h-3, are also responsible for inversions disrupting the factor VIII gene in haemophilia A. In addition, we have identified a reciprocal deletion in a girl and her mother, both of whom exhibit normal cognition and completely skewed XCI. The mother also had two spontaneous abortions. CONCLUSIONS: The phenotypic similarities among subjects with int22h-1/int22h-2-mediated Xq28 duplications suggest that such duplications are responsible for a novel XLID syndrome. The reciprocal deletion may not be associated with a clinical phenotype in carrier females due to skewed XCI, but may be lethal for males in utero. Advancements in array CGH technology have enabled the identification of such small, clinically relevant copy-number variants.

In vivo anti-tumor effect of expressing p14ARF-TAT using a FGF2-targeted cationic lipid vector.

PURPOSE: To develop an efficient and safe strategy to introduce a therapeutic gene into target cells in vivo for cancer therapy. The overall efficiency is based on proper selection of the delivery vector and expressed protein. METHODS: A plasmid coding for a specific cytotoxic fusion peptide, p14ARF-TAT, was evaluated in a xenograft mouse tumor model. The expressed peptide consisted of three domains, a secretory signal, a membrane permeability segment and a cytotoxic fragment. Gene expression was verified in U87-MG cells by Western blot and cytotoxicity confirmed with CyQuant assay. To improve the delivery, a FGF2 targeting peptide, MQLPLATC, was incorporated into the vector, which was evaluated using a luciferase-expressing plasmid. RESULTS: The luciferase activity in vitro was two-fold higher with the targeted formulations, and cytotoxicity was three-fold higher with expression of the p14ARF-TAT protein. A murine xenograph model of human glioma (U87-MG cells) tumors was used to address in vivo activity. FGF2-targeted lipoplexes demonstrated increased tumor volume reduction as compared to non-targeted formulations. RT-PCR and Western blot of tumor homogenizes indicated p14ARF-TAT expression in tumors along with other tissues. CONCLUSION: p14ARF-TAT was cytotoxic and is a promising approach when combined with an efficient targeting.

Polymeric nanoparticles containing conjugated phospholipase A2 for nonviral gene delivery.

Polyethylenimine (PEI) was conjugated to phospholipase A(2) (PLA(2)) in an effort to improve transfection efficiency. PLA(2) was conjugated to PEI using EDC as a coupling reagent. The activity of enzyme in the conjugate was measured. DNA condensation ability of the conjugate to polymer was determined. The resultant nanoparticles were characterized by dynamic and electrophoretic light scattering. Two reporter genes were used to evaluate transfection efficiency in human embryonic kidney (HEK293) and human hepatoma (HepG2) cell lines. Conjugate was shown to retain PLA(2) activity and its ability to condense plasmid DNA, resulting in nanoparticles of a similar size to native PEI. The results demonstrated at N/P ratios of 15 and 20 showed 13- and 8-fold increase in transfection efficiency, respectively, compared to the maximum transfection efficiency of PEI (N/P ratio of 5) in the whole range of N/P ratios tested, from 5 to 60 in HepG2 cells. Toxicity studies in HepG2 cells showed uncomplexed conjugate had similar toxicity as PEI, and when complexed with DNA the conjugate had a significantly reduced toxicity. The results clearly indicate the potential for this approach to improve efficiencies of nonviral gene delivery vectors.

Preparation and characterization of doxorubicin liposomes.

During nanoparticle system in drug delivery, liposomes were perhaps the best characterized and one of the first to be developed. Stealth liposomes (SLs), containing polyethylene glycol-conjugated lipid, which can form a hydro-layer around liposomes bilayer, have a long circulation time and hence result in enhanced drug efficiency. Doxorubicin (DOX), an effective anticancer drug, can be loaded into liposomes by transmembrane pH gradient method to get high encapsulation efficiency with high drug/lipid ratio. Liposomal doxorubicin is a successful clinical formulation, and also a perfect model drug system for cancer-therapy research. Here we described the preparation of SLs via extrusion, DOX loading by transmembrane pH gradient method, and characterization analysis, including phospholipid concentration, size, transmission electronic microscopy graph, encapsulation efficiency, and in vitro drug release.

Liposomal siRNA delivery.

With the recent discovery of small interfering RNA (siRNA), to silence the expression of genes in vitro and in vivo, there has been a need to deliver these molecules to the cell nucleus. Forming a lipid/nucleic acid complex has become a solution and is explored here. Certain methods and ideas are used, such as: the positive/negative electrostatic interaction with a cationic lipid and an anionic RNA molecule, the size of the lipid vesicle aiding the uptake target tissues, targeted lipoplexes which can increase efficiency, and the protection of the siRNA molecule from the natural defenses of the immune system. Many lipid formulations exist and can be experimented with to achieve varying results depending on the application.