This study evaluated the safety and efficacy of the Android Artificial Pancreas System (AAPS) in Brazilians with type 1 diabetes mellitus (T1D). A total of 371 participants were surveyed, including 62 AAPS users and 309 non-users. AAPS configurations included continuous glucose monitoring (CGM ), Bluetooth transmitter (MiaoMiao), and a non-automated insulin pump. AAPS users had a mean Time in Range (TIR) of 78.5% ± 16.6, with HbA1c levels decreasing from 7.3% ± 1.03 to 6.5% ± 0.7 (p < 0.001). Compared to non-AAPS users, AAPS users demonstrated better glycemic control, fewer severe hypoglycemic events (p = 0.006), and improved quality of life (p < 0.0001). However, 23.08% of AAPS users had a TIR below 70%, and time in level-2 hypoglycemia exceeded recommendations. These findings highlight AAPS as a low-cost alternative to commercial systems, with potential to expand access to automated therapy globally, particularly in resource-limited settings.
Antibody-drug conjugates (ADCs) represent a rapidly evolving therapeutic modality, combining the selective targeting of monoclonal antibodies with highly potent small molecule payloads. Their inherent structural complexity demands a sophisticated and multi-faceted bioanalytical approach spanning preclinical discovery through late-stage clinical development. This white paper, developed by the ADC Working Group of the AAPS bioanalytical community, comprising over 100 members from industry, contract research organizations (CROs), and regulatory agencies, provides updated recommendations for ADC bioanalysis. Building upon the foundational 2013 AAPS position paper and recent publications governing regulatory frameworks on PK considerations, this work addresses advances in bioanalytical quantitation strategies for total antibody (tAb), conjugated ADC, free (unconjugated) payload, and drug-to antibody ratio (DAR); novel immunogenicity assessment considerations; soluble target interference; critical reagent lifecycle management; payload-specific stability requirements; cross-validation strategies; and regulatory considerations. The recommendations presented herein reflect over a decade of scientific progress and are designed to serve as a comprehensive, empirically validated, and industry aligned bioanalytical framework for contemporary ADC drug development.
The Cross-Wellcome Africa Asian Programmes (AAPs) Acceleration of Genomics for Escalating Infectious Diseases (CAGED) Consortium is a collaboration among six institutions: the Africa Health Research Institute, the Center for Infectious Disease Research in Africa, the KEMRI-Wellcome Trust Research Programme, the Malawi Liverpool Wellcome Programme, the Mahidol Oxford Tropical Medicine Research Unit and the Oxford University Clinical Research Unit. The consortium focuses on studying pathogens posing major public health threats in Africa and Southeast Asia including chikungunya virus (CHIKV) dengue virus (DENV), multidrug-resistant (MDR) Klebsiella pneumoniae ( Kpn), and drug-resistant Mycobacterium tuberculosis (Mtb) with climate change considered one of the several factors influencing the distribution, transmission or burden of some of these pathogens. In this paper, we outline the consortium goals, planned activities, discuss challenges and future directions. By leveraging cross-continent expertise, CAGED aims to unravel the molecular epidemiology of escalating infectious diseases of public health importance in Africa and Southeast Asia, and build sustainable local sequencing capacity, helping the region better prepare for future emerging infectious disease outbreaks. The CAGED consortium seeks to leverage the capability of six institutions spread across Africa and South East Asia: the Africa Health Research Institute (AHRI) in South Africa, the Center for Infectious Disease Research in Africa (CIDRI-Africa) in the University of Cape Town in South Africa, KEMRI-Wellcome Trust Research Programme (KWTRP) in Kenya; the Malawi Liverpool Wellcome Programme (MLW) in Malawi; the Mahidol Oxford Tropical Medicine Research Unit (MORU) in Thailand and Laos; the Oxford University Clinical Research Unit (OUCRU) in Vietnam and Indonesia. The consortium seeks to scale up genomic surveillance for diseases driven by climate change and of public health importance in these regions. Specifically, we aim to advance multi-pathogen genomic epidemiology for characterizing transmission dynamics, tracking the emergence and spread of outbreak-associated variants, and assessing their potential to evade treatments, host immunity, and vaccines. We will use a multi-pathogen genomic surveillance approach to study the following pathogens: chikungunya (CHIKV), dengue (DENV), multidrug-resistant Klebsiella pneumoniae (Kpn), and drug-resistant Mycobacterium tuberculosis (Mtb) to bolster pathogen sequences in this region and inform improved diagnostics for these pathogens, while delineating drug resistance markers. We will share the data analysis tools developed from this study with the National Public Health Laboratory (NPHL) to improve their genomic surveillance capabilities. Additionally, we propose working closely with the policymakers to ensure that the results generated feed into policy-making decisions.
The artificial pancreas system (APS) has become an important technological approach for the treatment of type 1 diabetes mellitus (T1DM). However, whether patients with different baseline levels of coefficient of variation (CV) achieve different glycemic outcomes after APS use remains unclear. This study aims to investigate the impact of baseline CV levels on the effectiveness of APS therapy. This retrospective real-world study enrolled patients with T1DM who initiated AndroidAPS (AAPS) through online diabetes communities between January 2019 and April 2024. All participants continuously used AAPS for at least 3 months, and each open-loop interruption lasted no longer than 7 d. Original continuous glucose monitoring (CGM) data were obtained from the Nightscout cloud platform. CGM data from the first 7 d after AAPS initiation were used as baseline values, and the study period was defined as the first 3 months after AAPS initiation. According to internationally recommended cutoff values, patients were categorized into a glycemic stability group (CV≤36%) and a glycemic instability group (CV>36%) based on baseline CV. Changes in CGM metrics before and after APS therapy during the entire day, daytime (06:00-24:00), and nighttime (00:00-06:00) periods were compared between the 2 groups. The primary outcome measures were time in tight range (TITR; glucose range 70 to 140 mg/dL) and time in range (TIR; glucose range 70 to 180 mg/dL). Secondary outcome measures included time above range (TAR; classified as TAR1, TAR2, and TAR3), time below range (TBR; classified as TBR1 and TBR2), mean glucose level, CV, and estimated hemoglobin A1c (eA1c). Analysis of covariance was used to compare changes in glycemic metrics between the groups after 3 months of treatment, and multivariable linear regression models were constructed to analyze factors associated with CV. A total of 132 patients with T1DM were included, among whom 88 (66.67%) were assigned to the glycemic stability group and 44 (33.33%) to the glycemic instability group. No statistically significant differences were observed between the 2 groups in sex, age, body mass index (BMI), disease duration, glycated hemoglobin A1c (HbA1c) at diagnosis, or chronic complications (all P>0.05). After APS therapy, overall glycemic control significantly improved in both groups compared with baseline. After adjustment for baseline levels, the improvement in all-day TITR was significantly greater in the glycemic stability group than in the glycemic instability group, and TAR1 was significantly improved compared with baseline in the glycemic stability group (all P<0.05). Neither TBR1 nor TBR2 increased significantly after APS therapy in either group, indicating that glycemic improvement in the glycemic stability group was achieved without increasing the risk of hypoglycemia. Regarding glycemic variability, the all-day CV in the glycemic instability group significantly decreased after APS therapy compared with baseline (P<0.05). During daytime periods, after adjustment for baseline levels, no statistically significant differences were observed between the two groups in the degree of improvement in TITR, TAR, TBR, or mean glucose level (all P>0.05). During nighttime periods, improvements in TITR and TIR were significantly greater in the glycemic stability group than in the glycemic instability group, while reductions in TAR1 and TAR2 were also significantly greater in the glycemic stability group (all P<0.05). No statistically significant differences were found in hypoglycemia-related indicators (all P>0.05). Multivariable linear regression analysis showed that baseline eA1c was the only significant factor associated with CV (β=4.095, P<0.001). Age showed a negative correlation trend with CV (P=0.070), whereas sex and disease duration were not significantly associated with CV (all P>0.05). Baseline CV levels influence glycemic improvement after APS use in patients with T1DM. Patients with more stable glycemic variability are more likely to benefit from closed-loop systems without increasing hypoglycemia risk. In the promotion and clinical application of APS, baseline glycemic variability characteristics should be fully considered to optimize management and treatment strategies. 目的: 人工胰腺系统(artificial pancreas system，APS)已成为1型糖尿病(type 1 diabetes mellitus，T1DM)治疗的重要技术手段。然而，不同血糖变异系数(coefficient of variation，CV)水平的患者在使用APS后是否存在疗效差异尚不明确。本研究旨在探讨基线CV水平对APS治疗效果的影响。方法: 本研究为一项回顾性真实世界研究，纳入2019年1月至2024年4月期间在线上糖尿病社区中初次启用AndroidAPS(AAPS)的T1DM患者，所有参与者均连续使用AAPS≥3个月，且单次开环时间不超过7 d。原始连续葡萄糖监测(continuous glucose monitoring，CGM)数据来源于Nightscout云平台。以AAPS启用后前7 d的CGM数据作为基线，研究期定义为启用AAPS后的前3个月。根据国际共识推荐的临界值，将患者按基线CV分为血糖稳定组(CV≤36%)与血糖不稳定组(CV>36%)。比较2组在APS治疗前后全天、日间(06:00-24:00)及夜间(00:00-06:00)的CGM指标变化。主要结局指标为葡萄糖在严格目标范围内时间(time in tight range，TITR;血糖范围为70~140 mg/dL)和葡萄糖在目标范围内时间(time in range，TIR;血糖范围为70~180 mg/dL);次要结局指标包括葡萄糖高于目标范围时间(time above range，TAR;分为TAR1、TAR2、TAR3)、葡萄糖低于目标范围时间(time below range，TBR;分为TBR1、TBR2)、平均血糖、CV、预估糖化血红蛋白(estimated percentage of hemoglobin A1c，eA1c)。采用协方差分析比较2组在治疗后3个月指标变化的差异，并构建多元线性回归模型分析影响CV的相关因素。结果: 共纳入132例T1DM患者，其中血糖稳定组88例(66.67%)，血糖不稳定组44例(33.33%)。2组在性别、年龄、体重指数(body mass index，BMI)、病程、起病时糖化血红蛋白(glycated hemoglobin A1c，HbA1c)及慢性并发症方面的差异均无统计学意义(均P>0.05)。APS治疗后，2组患者全天血糖控制均较基线显著改善。经校正基线水平后，血糖稳定组全天TITR改善幅度显著高于血糖不稳定组，且血糖稳定组的TAR1与基线相比显著改善(均P<0.05)。APS治疗后2组TBR1和TBR2均未见显著增加，提示血糖稳定组血糖改善且没有增加低血糖风险。在血糖波动性方面，APS治疗后血糖不稳定组的全天CV较基线显著下降(P<0.05)。日间时段，校正基线水平后，2组患者TITR、TAR、TBR及平均血糖方面改善幅度的差异均无统计学意义(均P>0.05)。夜间时段，血糖稳定组TITR和TIR改善幅度均显著大于血糖不稳定组，同时TAR1和TAR2下降幅度均显著大于血糖不稳定组(均P<0.05)，低血糖相关指标差异均无统计学意义(均P>0.05)。多元线性回归分析显示，基线eA1c是CV的唯一显著影响因素(β=4.095，P<0.001)，年龄与CV呈负相关趋势(P=0.070)，而性别及病程与CV均无显著相关性(均P>0.05)。结论: 基线CV水平影响T1DM患者使用APS后的血糖改善效果。血糖稳定的患者更易从闭环系统中获益，且不会增加低血糖风险。在APS推广和临床实践中，应充分考虑患者基线血糖波动特征，优化管理和治疗策略。.
Atypical action potentials (aAPs) are fast depolarizing electrical spikes recorded from the cell body, with a smaller amplitude. Despite varying in the generating mechanisms, aAPs have been reported in various brain cell types, including neurons, oligodendrocyte precursor cells (OPCs), and glioma cells. In this mini-review, we summarize the mechanisms and physiological functions of aAPs and outline their contributions to neurological diseases, particularly in glioma pathology. aAPs have been observed in mature brains, arising from mechanisms such as ectopic depolarizations and gap junction coupling, thereby supporting synaptic integration and network synchrony. It is also a signature of immature neurons in development. Subsets of NG2+ OPCs and immature oligodendrocyte-lineage cells exhibit state-, region-dependent excitability, ranging from subthreshold depolarizations to AP-like events, with potential roles in neuron-glial communication, ischemic vulnerability, and myelination. Accumulating human studies have demonstrated that glioma cells generate aAPs, while until recently their molecular profile was characterized by patch-seq. In IDH-mutant glioma, aAP cells exhibit a mixed GABAergic and OPC signature. At the leading edge (LE) of IDH-wild-type gliomas, aAPs are present in both adjacent non-tumor cells and glioblastoma cells (GBCs) across diverse GBC states, yet exhibit reduced proliferation and increased inflammatory signaling. In conclusion, aAPs are a recurrent but context-dependent electrophysiological feature observed in subsets of glioma cells, and may indicate an active role in network integration and active release. Dissecting the differential roles of aAP and no-aAP GBCs through targeted manipulations informed by transcriptomic results may reveal crucial mechanisms underlying multifaceted tumor-neuron crosstalk in glioma progression.
Polysaccharide‑sodium alginate complexes system can improve the poor stability of anthocyanins, making anthocyanins become a potential and stable pH indicator. In this study, an intelligent pH indicator film based on Anemarrhena asphodeloides polysaccharides (AAPs)/sodium alginate (SA) incorporating black rice anthocyanins (BRAs) was designed to monitor pork freshness. The intelligent film (2%AAPs-SA-BRAs film) showed excellent barrier performance (lower water vapor permeability and water vapor adsorption). AAPs could improve moisture content, water solubility, thermal stability, color stability, mechanical properties, pH sensitivity, and ammonia sensitivity. Moreover, FT-IR spectroscopy further indicated the hydrogen bonds among film-forming components. The physicochemical properties of the indicator 2%AAPs-SA-BRAs film were the strongest. Furthermore, AAPs could increase the compactness of the cross-section and crystallinity of the intelligent indicator films. The indicator AAPs-SA-BRAs films exhibited a strong potential to effectively indicate the freshness of pork in intelligent food packaging during the storage of pork.
Open-source Android artificial pancreas systems (AAPS) have demonstrated benefits in glycaemic control among children and adolescents with type 1 diabetes (T1D). However, evidence comparing glycaemic outcomes between school days and holidays remains limited. This study investigated whether glycaemic outcomes differed between school days and holidays in children and adolescents with T1D using AAPS. This real-world retrospective study included school-aged participants with T1D aged 6-19 years who had used AAPS for more than 3 months. Continuous glucose monitoring (CGM) data were categorized as school days or holidays, and glycaemic outcomes were analysed. 55 participants included, of whom 20 (36.36%) were male. Median total duration of AAPS use was 209.39 [170.66, 289.97] days. Glycaemic metrics, including time in range (TIR), time in tight range (TITR), time above range (TAR), time below range (TBR), glucose management indicator (GMI), mean glucose, standard deviation (SD), coefficient of variation (CV), low blood glucose index (LBGI), and high blood glucose index (HBGI), showed no significant differences between school days and holidays across whole day, daytime, and nighttime periods (p > 0.05). Multivariable logistic regression analyses showed that longer nighttime sleep duration was associated with higher TITR (adjusted OR 2.29, 95% CI 1.29-4.47, p = 0.008) and TIR (adjusted OR 2.07, 95% CI 1.17-3.96, p = 0.018) achievement during school days. CGM-derived glycaemic outcomes were comparable between school days and holidays in participants with T1D using AAPS. Longer nighttime sleep during school days was associated with higher TITR and TIR achievement.
Amino acid permeases (AAPs) are transporters involved in the uptake, transport, and remobilization of amino acids across various plant tissues and play a vital role in nitrogen metabolism and plant development. This review presents recent findings on the function and regulation of AAPs in various plant species, highlighting their roles in seed development, grain yield, grain quality, response to abiotic stresses (e.g., drought, salinity, nutrient stress) and biotic stresses (e.g., nematode infestations, verticillium wilt), source-sink transport, hormonal crosstalk, senescence and N use efficiency (NUE). Functional characterization of AAPs through overexpression and knockout mutants has provided insights into their specific contributions to amino acid homeostasis and stress response. This review aims to unleash the potential of AAPs in improving NUE and crop yield, with future studies focusing on the complex interplay between AAPs, phytohormonal signalling, and metabolic pathways. Profound knowledge of AAP-mediated processes will enhance crop improvement strategies to increase yield and resilience in agricultural systems. The online version contains supplementary material available at 10.1007/s12298-026-01735-1.
Nα-Aroyl-N-aryl-phenylalanine amides (AAPs) are a class of antimycobacterial substances that inhibit the RNA polymerase and are effective against various pathogenic and opportunistic mycobacteria, including Mycobacterium tuberculosis, Mycobacterium abscessus, and Mycobacterium avium. Further development of these promising compounds, however, has been hindered by their low microsomal stability, leading to insufficient bioavailability. The present study investigates the mechanism by which microsomal enzymes metabolically degrade AAPs and identifies the resulting metabolites using LC-MS/MS. Rapid oxidation of the ortho-phenylenediamine structure, present in various substances in this class, plays a key role in this process. Additionally, we demonstrated in vitro and in vivo that cytochrome P450 enzyme inhibitors significantly slow the degradation of AAPs. Identification of metabolites will inform further chemical modification of AAPs to achieve metabolic stability.
Existing deep learning strategies for identifying bioactive peptides (BAPs) are often limited by single-task models and shallow sequence-based features, which restricts their generalizability. This study introduced an auto-encoder based deep learning framework (BioPepAE) that leverages peptide atomic 3D information from AlphaFold 3 to enable recognition of multiple types of BAPs, including anti-hypertensive peptides (AHPs), anti-oxidant peptides (AOPs), and anti-aging peptides (AAPs). BioPepAE achieved high accuracy (94.65% for AHPs, 95.47% for AOPs, 92.86% for AAPs) and demonstrated strong generalization on independent tests. BioPepAE identified 8 AHPs, 13 AOPs, and 5 AAPs from wheat germ protein hydrolysates, and subsequent in vitro assays confirmed the bioactivity of randomly selected peptides, thus validating its predictive accuracy and practical utility. Moreover, BioPepAE requires no complex parameter tuning for identifying different BAPs. This study presents a robust and versatile framework for the universal and accurate identification of BAPs by integrating 3D structural information with deep learning.
Atypical antipsychotics (AAPs) are increasingly prescribed for bipolar spectrum disorders in children and adolescents. This study aimed to investigate the prevalence and trends of AAP prescriptions among Korean children and adolescents with bipolar spectrum disorders. We analyzed data from the Korean National Health Insurance Review and Assessment Service to assess AAP use among Koreans aged 0-18 years with bipolar spectrum disorders between 2010 and 2022. This population-based study used an annual cross-sectional assessment to evaluate trends in AAP prescription. The prevalence of AAP prescriptions for children and adolescents with bipolar spectrum disorders increased over the 13-year study period, rising from 0.14 in 2010 up to 1.23 per 1000 persons in 2022. During this time, the dominant AAP shifted from risperidone to aripiprazole. Data from 2022 revealed that the most prescribed AAP for children was aripiprazole, followed by risperidone, quetiapine, and olanzapine. Children and adolescents with bipolar spectrum disorders and psychiatric comorbidities, particularly ADHD, were prescribed AAPs more frequently (p < 0.001). The prescription of AAPs in Korean children and adolescents with bipolar spectrum disorders has increased over the last decade. This trend was particularly pronounced among individuals with psychiatric comorbidities, especially ADHD. Future research is needed to develop more evidence-based AAP treatments for bipolar spectrum disorders in this population.
Acid phosphatase (ACP) is a clinically important enzyme whose early-stage detection is hindered by its extremely low abundance, nonspecific tissue distribution, and rapid loss of activity under conventional analytical conditions. Herein, we present a target-driven in situ nanozyme synthesis strategy that enables rapid and ultrasensitive point-of-care testing (POCT) of ACP. In this approach, ACP catalyzes the hydrolysis of L-ascorbic acid 2-phosphate sesquimagnesium (AAPS), producing ascorbic acid (AA). The generated AA partially reduces Fe3+ ions to Fe2+, thereby initiating alkaline co-precipitation and in situ formation of Fe3O4 nanoparticles. Polyvinylpyrrolidone (PVP) stabilizes the nanoparticles and preserves catalytic accessibility, while their intrinsic magnetism allows for efficient magnetic separation to eliminate matrix interference. The resulting Fe3O4@PVP nanozymes display pronounced peroxidase-like activity, catalyzing hydrogen-peroxide-mediated oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). Quantitative readout can be achieved using either spectrophotometric analysis or smartphone imaging. The sensing platform achieves a detection limit of 0.021 U/L within 40 min and demonstrates excellent sensitivity, selectivity, and operational robustness. Successful validation in human serum confirms its clinical feasibility, while smartphone-based imaging enables portable and low-cost quantification suitable for decentralized diagnostics. Collectively, this work establishes a generalizable paradigm for target-triggered nanozyme generation aimed at detecting low-abundance and labile biomarkers.
On November 2025, AAPS PharmSci 360 convened a symposium that included experts in the application of various types of New Approach Methodologies (NAMs). They shared their experiences and insights on topics that included microphysiological systems (MPS), the use of 3D organoids, and in silico tools. MPS systems were explored from the perspective of their testing and qualification through an academia-industry-government tissue chip testing consortium whose mission is to perform context-of-use-based testing of MPS and conduct comparative evaluations to support the use of MPS systems in safety assessments. 3D organoids were described and insights shared on how and when they may provide an appropriate tool for evaluating drug safety and effectiveness, and their use in supporting personalized medicine. Regarding in silico tools, examples were provided to describe their growing utility in predicting drug toxicity, population variability, and its potential benefits over traditional evidence-based toxicology. These tools include in silico models (e.g., physiologically based pharmacokinetic models), Artificial Intelligence (AI), and Machine Learning (ML) which, unlike other aspects of model informed drug development, reduce reliance on predefined models and allows for the integration of diverse sources of data. Computationally, these tools can generate predictions in hours where it would otherwise have taken weeks or months (and extensive experimentation). Within this meeting report, we highlight the key issues discussed during that symposium and share additional aspects to consider when developing a NAMs-based roadmap for specific contexts of use.
To improve the performance of pressurized metered dose inhalers (pMDIs) a better mechanistic understanding of early deposition within the device and upper airways is needed to move toward more efficient inhalation therapies. The present work aimed to address the longstanding gap between plume geometry (PG) measurements and pulmonary drug delivery by evaluating PG with the Plume Induction Port Evaluator (PIPE), a mass-based method that characterizes plume angles under flow and within a restricted geometry. Three Rhodamine B solution pMDI formulations containing 2.49, 9.99, and 19.99% ethanol were evaluated at 5, 25, and 37 °C. PG was characterized by high-speed laser imaging (HSLI, 0 L/min) and by PIPE connected to a Next Generation Impactor (NGI, 30 L/min). Formulation vapor pressure, droplet size by laser diffraction, aerodynamic particle size by cascade impaction, early deposition, fine particle fraction (FPF), and respirable fraction (RF) were also determined. Deposition patterns within PIPE were log-normally distributed and consistently downward oriented, allowing calculation of mass median plume angle (MMPA) under flow. HSLI and MMPA showed opposite responses to formulation vapor pressure, where higher vapor pressure produced narrower optical PG but wider mass-based plume angles. A multivariable model incorporating MMPA, volume median diameter, formulation vapor pressure, and the MMPA × pressure interaction predicted RF with strong agreement (R2 = 0.919). These results show that early deposition in pMDIs is not governed by particle size alone, but also by plume trajectory under inhalation flow.
The adsorption behavior of recombinant human growth hormone (r-hGH) on cationic (PS+, amidine) and anionic (PS-, sulfate) polystyrene surfaces was investigated under varying solution pH conditions (surface charge), ionic strengths (0.0075 M and 0.075 M), and solvent dielectric constants to elucidate the adsorption mechanism governed by physicochemical interactions. In addition, desorption upon dilution was also examined. The studies utilized 125I-labeled r-hGH and demonstrated that adsorption of r-hGH onto both PS⁺ and PS⁻ surfaces was influenced by solution conditions, ionic strength, and solvent dielectric constant. Marked electrostatic repulsion accompanied by decreased adsorption was observed on PS⁺ surfaces at pH 2.5 and on PS⁻ surfaces at pH 7.2. Adsorption was highest near the isoelectric point of r-hGH but decreased with increasing ionic strength. PS⁺ and PS⁻ surfaces showed significantly different adsorption profiles, resulting from the combined effects of hydrophobic and electrostatic interactions involving r-hGH, the change in r-hGH confirmation in solution, and the structural characteristics of the surface adsorbed protein. Studies were also carried out to assess the effect of the presence of proteins and surfactants at an ionic strength of 0.0075 M over a pH range of 2.5-7.2. Under conditions where both proteins inhibited adsorption, β-casein exhibited a greater inhibitory effect than BSA. Surfactants exhibited concentration dependent effects, with Tween 20 producing stronger inhibition than Pluronic F-68. Overall, these results demonstrate that r-hGH adsorption onto charged polystyrene surfaces is influenced by a complex interplay of charged interactions, hydrophobic effects, competitive adsorption, surfactant effects, and protein conformational stability.
Aesthetic surgery tourism has become a popular option for patients due to discounted procedures. This single-center retrospective study recorded outcomes in patients presenting with complications after traveling for aesthetic surgery. Aesthetic surgery tourism patient demographics and outcomes were retrospectively reviewed between January 2021 and December 2024 at Henry Ford Health (HFH). Data were compiled including surgery type, complications, number of emergency room (ER) visits, interventions, admission length of stay (LOS), hospital and physician charges. From 2021 to 2024, 44 patients were seen by the plastic surgery team at HFH for complications following aesthetic surgery tourism. Of all patients, 54.5% had abdominoplasty, 40.9% liposuction, 25% Brazilian butt lift (BBL), 15.9% breast, 2.3% jaw surgery, and 2.3% buttock implant. Complications were infection (52.3%), pulmonary embolism (6.8%), seroma/fluid collection (52.3%), abscess (18.2%), wound dehiscence (20.5%), and foreign body/retained suture/retained drain (6.8%). Average number of ER visits was 1.75. Average admission LOS was 5 days. Patients requiring operating room or bedside intervention were 25% and 61.4%, respectively. Total hospital charges were $1,424,869.38; average per patient was $34,752.91. Total physician charges were $193,773.25; average per patient was $4726.18. Aesthetic surgery tourism is more affordable for patients short term, but the potential complications can jeopardize patient safety and place an increasing financial burden on our healthcare system. It is crucial to educate patients on the risks of traveling for aesthetic surgery. Potential interventions include education at pre-operative clearance appointments, providing options to consult a US board-certified plastic surgeon before traveling, and increasing domestic regulations. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Targeted drug delivery systems play a crucial role in improving the effectiveness and precision of cancer treatments. Liposomes have been widely investigated as drug carriers due to their versatility. Traditional methods for functionalizing liposomes involve covalent bonding of targeting ligands, which, while effective, can be complex and may affect the activity of the ligands. In contrast, non-covalent peptide insertion offers a simpler, more adaptable approach for incorporating targeting peptides into liposomal membranes using mechanisms such as hydrophobic interactions and electrostatic forces. This review examines non-covalent peptide-liposome interactions as the primary focus. We analyze mechanisms, incorporation techniques, and therapeutic applications with emphasis on formulation-relevant criteria including stability, manufacturability, and clinical translation. Critical evaluation of comparative advantages and limitations of each strategy provides decision frameworks for formulation scientists. We also address manufacturing challenges, quality control strategies, and regulatory considerations that influence clinical translation.
Direct compression is a generally preferred for tablet manufacturing method. However, it demands excipients with balanced flowability, compressibility, and packing properties. Microcrystalline cellulose (MCC) and calcium sulphate (CaSO₄) have balancing functionalities but individual limitations. To develop and optimize a novel MCC-CaSO₄ co-processed excipient (MCCASUL) for direct compression application using the SeDeM Expert System. To determine critical material attributes (CMA),12 SeDeM parameters were used to categorised MCC and CaSO₄. Functional indices, Parametric Profile Index (IPP), and Good Compression Index (IGC) were also calculated. To overcome the compressibility deficiency of CaSO₄ the required proportion of MCC was determined using SeDeM dilution potential equation. Co-dispersion method was used to prepare 9 MCCASUL batch with varying MCC:CaSO₄ ratios and further evaluated using SeDeM indices. Further characterization by FTIR, DSC, SEM, Heckel, and Kawakita analyses were performed for the optimised batch. MCC was more compressible (ѱc = 7.00) than CaSO₄ (ѱc = 4.67). The theoretical amount of correction for MCC was 14.16% among the batch preparation made, MCCASUL 4 exhibited the best results (IPP = 6.50, ѱf = 7.46, ѱc = 6.31). FTIR analysis proved the compatibility between the materials, DSC analysis revealed that modified thermal characteristics were stable, and SEM revealed improved morphology. With SeDeM expert System, co-processing yielded MCCASUL a highly versatile excipient that exhibited superior flowability, compressibility and stability and showed immense potential for direct compression tablet production.
Amphotericin B exhibits dose-dependent nephrotoxicity and hepatotoxicity due to its non-selective interaction with mammalian cholesterol. The aim of the present study was to develop an Amphotericin B-cholesterol co-encapsulated albumin hydrogel-based injectable depot formulation to achieve prolonged plasma drug concentrations with reduced toxicity. Amphotericin B-loaded polymeric nanoparticles (Amphotericin B-PNs) were prepared by the nanoprecipitation method. Cholesterol co-encapsulated nanoformulation has been able to keep Amphotericin B in a less aggregated state (aggregation ratio -1.40), exhibited less hemolysis (< 10%) in rat erythrocytes, higher cytocompatibility in HEK 293 T and RAW 264.7 cell lines, as well as time-dependent increased intracellular accumulation of C6 loaded nanoparticles. Amphotericin B-PN-loaded albumin hydrogel was prepared by an ethanol-induced gelation process. Nanoparticle-loaded hydrogel exhibited sustained drug release, and at the end of one week ~ 60% of Amphotericin B was released. Hydrogel formulations have shown improved pharmacokinetic parameters with prolonged drug release till the end of the 14th day. The cholesterol co-encapsulated hydrogel has also shown reduced organ toxicity and improved safety against oxidative stress, as revealed by biochemical (creatinine, BUN, ALT, and AST) and ROS (GSH, catalase, NO, and MDA) scavenging assays. Overall, it can be concluded that the Amphotericin B-PN-loaded albumin hydrogel could be a potential delivery system for the long-acting release of Amphotericin B with reduced toxicity.
Hesperetin and cannabidiol (CBD) are promising plant-derived bioactives whose oral performance is limited by poor aqueous solubility. To address the shared biopharmaceutical limitations of both compounds, amorphous PVP K30-phosphatidylcholine dispersions were prepared via hot-melt extrusion (HME). A Box-Behnken design (DoE) was applied to investigate the impact of (i) total API load (hesperetin:CBD mass ratio 1:1), (ii) phospholipid content in the carrier, and (iii) extrusion temperature on the solubility of both actives. The resulting extrudates were characterized by XRPD, DSC, and FT-IR/ATR. Solubility and dissolution profiles were evaluated in phosphate buffer (pH 6.8). In vitro passive permeability was assessed using PAMPA GIT model. DoE indicated that API load and phospholipid content were statistically significant factors for solubility of both hesperetin and CBD, whereas extrusion temperature was not significant within the studied range. XRPD confirmed amorphization for all formulations except F6, which contained a minor residual crystalline fraction of hesperetin. DSC revealed single glass-transition events, supporting good miscibility. The best-performing formulation (F7; 15% APIs, 20% phospholipid, 165°C) achieved solubilities of 4.934 mg/mL (hesperetin; 987-fold increase) and 4.314 mg/mL (CBD; 66,369-fold increase) and showed the highest permeability in PAMPA GIT model. HME-produced PVP K30-phosphatidylcholine amorphous dispersions substantially improved the solubility, dissolution behavior, and in vitro permeability of hesperetin and CBD, highlighting polymer-phospholipid amorphous dispersions as a promising solubility-enhancing platform for delivery of poorly soluble.