Development and Validation of an Endometriosis Diagnostic Method Based on Serum Biomarkers and Clinical Variables.

Endometriosis affects more than 10% of women of reproductive age, significantly impacting their quality of life. Diagnosis typically takes 4 to 11 years from symptom onset. The gold standard for diagnosing this disease, laparoscopy, is invasive, contributing to this delay in diagnosis. Two studies were conducted to develop a diagnostic test based on the combination of serum biomarkers and clinical variables. Study 1, the development study, aimed to: (i) confirm the ability of CA125, BDNF and clinical variables to differentiate between cases and controls, and (ii) develop a diagnostic algorithm based on these results. Study 2 validated the clinical performance of the developed in vitro diagnostic (IVD) test in diagnosing endometriosis. Serum samples and clinical variables extracted from psychometric questionnaires were obtained from the Oxford Endometriosis CaRe Centre biobank (UK). Case/control classification was performed based on laparoscopy and histological verification of the excised lesions. Studies 1 and 2 included n = 204 and n = 79 patients, respectively. Study 1 found a statistically significant difference between cases and controls for levels of both biomarkers. Of the assessed clinical variables from the patients' medical histories, six were found to be significantly different between endometriosis cases and controls. CA125, BDNF and these six clinical variables were combined into a multivariable prediction model. In Study 2, the IVD test demonstrated sensitivity and specificity values of 46.2% (25.5-66.8%) and 100% (86.7-100%), respectively. Due to its high specificity, this IVD test is a simple and accurate rule-in test for early disease identification, even in the presence of non-specific symptoms.

The Charlotte Project: Recommendations for patient-reported outcomes and clinical parameters in Dravet syndrome through a qualitative and Delphi consensus study.

Objective: The appropriate management of patients with Dravet Syndrome (DS) is challenging, given the severity of symptoms and the burden of the disease for patients and caregivers. This study aimed to identify, through a qualitative methodology and a Delphi consensus-driven process, a set of recommendations for the management of DS to guide clinicians in the assessment of the clinical condition and quality of life (QoL) of DS patients, with a special focus on patient- and caregiver-reported outcomes (PROs). Methods: This study was conducted in five phases, led by a multidisciplinary scientific committee (SC) including pediatric neurologists, epileptologists, a neuropsychologist, an epilepsy nurse, and members of DS patient advocates. In phases 1 and 2, a questionnaire related to patients' QoL was prepared and answered by caregivers and the SC. In phase 3, the SC generated, based on these answers and on a focus group discussion, a 70-item Delphi questionnaire, covering six topic categories on a nine-point Likert scale. In phase 4, 32 panelists, from different Spanish institutions and with a multidisciplinary background, answered the questionnaire. Consensus was obtained and defined as strong or moderate if ≥80% and 67-79% of panelists, respectively, rated the statement with ≥7. Phase 5 consisted of the preparation of the manuscript. Results: The panelists agreed on a total of 69 items (98.6%), 54 (77.14%), and 15 (21.43%) with strong and moderate consensus, respectively. The experts' recommendations included the need for frequent assessment of patient and caregivers QoL parameters. The experts agreed that QoL should be assessed through specific questionnaires covering different domains. Likewise, the results showed consensus regarding the regular evaluation of several clinical parameters related to neurodevelopment, attention, behavior, other comorbidities, and sudden unexpected death in epilepsy (SUDEP). A consensus was also reached on the instruments, specific parameters, and caregivers' education in the routine clinical management of patients with DS. Conclusions: This consensus resulted in a set of recommendations for the assessment of clinical and QoL parameters, including PROs, related to the general evaluation of QoL, neurodevelopment, attention, behavior, other comorbidities affecting QoL, SUDEP, and QoL of caregivers/relatives and patients with DS.

The Impact of Residential Segregation on Pancreatic Cancer Diagnosis, Treatment, and Mortality.

BACKGROUND: Disparities in pancreatic cancer outcomes between black and white patients are well documented. This study aimed to use a more novel index to examine the impact of racial segregation on the diagnosis, management, and outcomes of pancreatic cancer in black patients compared with white patients. METHODS: Black and white adults with pancreatic cancer in urban counties were identified using data from the 2018 submission of the Surveillance, Epidemiology and End Results (SEER) Program and the 2010 Census. The racial index of dissimilarity (IoD), a validated proxy of racial segregation, was used to assess the evenness with which whites and blacks are distributed across census tracts in each county. Multivariate Poisson regression was performed, and stepwise models were constructed for each of the outcomes. Overall survival was studied using the Kaplan-Meier method. RESULTS: The study enrolled 60,172 adults with a diagnosis of pancreatic cancer between 2005 and 2015. Overall, the black patients (13.8% of the cohort) lived in more segregated areas (IoD, 0.67 vs 0.61; p < 0.05). They were less likely to undergo surgery for localized disease (relative risk [RR], 0.80; 95% confidence interval [CI], 0.76-0.83) and more frequently had a diagnosis of advanced-stage disease (RR, 1.09; 95% CI, 1.01-1.19) with increasing segregation. They also had shorter survival times (9.8 vs 11.4 months; p < 0.05). CONCLUSIONS: Disparities in advanced-stage disease at diagnosis, surgery for localized disease, and overall survival are directly related to the degree of residential segregation, a proxy for structural racism. In searching for solutions to this problem, it is important to account for the historical marginalization of black Americans.

Does the Halo Effect for Level 1 Trauma Centers Apply to High-Acuity Nonsurgical Admissions?

CONTEXT: The halo effect describes the improved surgical outcomes at trauma centers for nontrauma conditions. OBJECTIVE: To determine whether level 1 trauma centers have improved inpatient mortality for common but high-acuity nonsurgical diagnoses (eg, acute myocardial infarction [AMI], congestive heart failure [CHF], and pneumonia [PNA]) compared with non--level 1 trauma centers. METHODS: The authors conducted a population-based, retrospective cohort study analyzing data from the Healthcare Cost and Utilization Project State Inpatient Database and the American Hospital Association Annual Survey Database. Patients who were admitted with AMI, CHF, and PNA between 2006-2011 in Florida and California were included. Level 1 trauma centers were matched to non-level 1 trauma centers using propensity scoring. The primary outcome was risk-adjusted inpatient mortality for each diagnosis (AMI, CHF, or PNA). RESULTS: Of the 190,474 patients who were hospitalized for AMI, CHF, or PNA, 94,037 patients (49%) underwent treatment at level 1 trauma centers. The inpatient mortality rates at level 1 trauma centers vs non-level 1 trauma centers for patients with AMI was 8.10% vs 8.40%, respectively (P=.73); for patients with CHF, 2.26% vs 2.71% (P=.90); and for patients with PNA, 2.30% vs 2.70% (P=.25). CONCLUSION: Level 1 trauma center designation was not associated with improved mortality for high-acuity, nonsurgical medical conditions in this study.

Liquid biopsy for the detection and management of surgically resectable tumors.

BACKGROUND: Traditional biopsies have numerous limitations in the developing era of precision medicine, with cancer treatment that relies on biomarkers to guide therapy. Tumor heterogeneity raises the potential for sampling error with the use of traditional biopsy of the primary tumor. Moreover, tumors continuously evolve as new clones arise in the natural course of the disease and under the pressure of treatment. Since traditional biopsy is invasive, it is neither feasible nor practical to perform serial biopsies to guide treatment in real time. PURPOSE: The current manuscript will review the most commonly used types of liquid biopsy and how these apply to surgical patients in terms of diagnosis, prediction of outcome, and guiding therapy. CONCLUSIONS: Liquid biopsy has the potential to overcome many of the limitations of traditional biopsy as a highly tailored, minimally invasive, and cost-effective method to screen and monitor response to treatment. However, many challenges still need to be overcome before liquid biopsy becomes a reliable and widely available option.

The importance of circulating and disseminated tumor cells in pancreatic cancer.

Pancreatic cancer is a lethal disease in a large part due to the systemic nature at the time of diagnosis. In those patients who undergo a potentially curative resection of pancreatic cancer, the overwhelming majority will have systemic relapse. Circulating tumor cells are an important mediator of the development of metastases. Circulating tumor cells have been identified in patients with clinically localized resectable pancreatic cancer and exist as several phenotypes. Mesenchymal and stem cell-like phenotypes of circulating tumor cells predict early recurrence and worse survival. This review focuses on the current understanding of circulating tumor cells in pancreatic cancer and how this information can be used in developing more effective therapy in the future.

Discordance between surgical care improvement project adherence and postoperative outcomes: implications for new Joint Commission standards.

BACKGROUND: Infectious (INF) and venous thromboembolism (VTE) complication rates are targeted by surgical care improvement project (SCIP) INF and SCIP VTE measures. We analyzed how adherence to SCIP INF and SCIP VTE affects targeted postoperative outcomes (wound complication [WC], deep vein thrombosis, and pulmonary embolism [PE]) using all-payer data. MATERIALS AND METHODS: A retrospective review (2007-2011) was conducted using Healthcare Cost and Utilization Project State Inpatient Database Florida and Medicare's Hospital Compare. The association between SCIP adherence rates and outcomes across 355 included surgical procedures was measured using multilevel mixed-effects linear regression models. RESULTS: One hundred sixty acute care hospitals and 779,922 patients were included. Over 5 y, SCIP INF-1, -2, and -3 adherence improved by 12.5%, 8.0%, and 20.9%, respectively, whereas postoperative WC rate decreased by 14.8%. When controlling for time, SCIP INF-1 adherence was associated with improvement of postoperative WC rates (ß = -0.0044, P = 0.005), whereas SCIP INF-2 adherence was associated with increased WCs (ß = 0.0031, P = 0.018). SCIP VTE-1, -2 adherence improved by 14.6% and 20.2%, respectively, whereas postoperative deep vein thrombosis rate increased by 7.1% and postoperative PE rate increased by 3.7%. SCIP VTE-1 and -2 adherence were both associated with increased postoperative PE when controlling for time (SCIP VTE-1: ß = 0.0019, P < 0.001; SCIP VTE-2: ß = 0.0015, P < 0.001). Readmission analysis found SCIP INF-1 adherence to be associated with improved 30-d WC rates when controlling for patient and hospital characteristics (ß = -0.0021, P = 0.032), whereas SCIP INF-3 adherence was associated with increased 30-d WC rates when controlling for time (ß = 0.0007, P = 0.04). CONCLUSIONS: Only SCIP INF-1 adherence was associated with improved outcomes. The Joint Commission has retired SCIP INF-2, -3, and SCIP VTE-2 and made SCIP INF-1 and VTE-1 reporting optional. Our study supports continued reporting of SCIP INF-1.

Intracellular responsive dual delivery by endosomolytic polyplexes carrying DNA anchored porous silicon nanoparticles.

Bioresponsive cytosolic nanobased multidelivery has been emerging as an enormously challenging novel concept due to the intrinsic protective barriers of the cells and hardly controllable performances of nanomaterials. Here, we present a new paradigm to advance nano-in-nano integration technology amenable to create multifunctional nanovehicles showing considerable promise to overcome restrictions of intracellular delivery, solve impediments of endosomal localization and aid effectual tracking of nanoparticles. A redox responsive intercalator chemistry comprised of cystine and 9-aminoacridine is designed as a cross-linker to cap carboxylated porous silicon nanoparticles with DNA. These intelligent nanocarriers are then encapsulated within novel one-pot electrostatically complexed nano-networks made of a zwitterionic amino acid (cysteine), an anionic bioadhesive polymer (poly(methyl vinyl ether-alt-maleic acid)) and a cationic endosomolytic polymer (polyethyleneimine). This combined nanocomposite is successfully tested for the co-delivery of hydrophobic (sorafenib) or hydrophilic (calcein) molecules loaded within the porous core, and an imaging agent covalently integrated into the polyplex shell by click chemistry. High loading capacity, low cyto- and hemo-toxicity, glutathione responsive on-command drug release, and superior cytosolic delivery are shown as achievable key features of the proposed formulation. Overall, formulating drug molecules, DNA and imaging agents, without any interference, in a physico-chemically optimized carrier may open a path towards broad applicability of these cost-effective multivalent nanocomposites for treating different diseases.

Transient atrial fibrillation after open abdominal aortic revascularization surgery is associated with increased length of stay, mortality, and readmission rates.

BACKGROUND: It is well established that transient postoperative atrial fibrillation (TPAF) is associated with adverse postoperative outcomes after major cardiac and noncardiac operations. The purpose of this study was to elucidate the incidence, impact, and risk factors associated with the development of TPAF in patients undergoing revascularization surgery for occlusive diseases of the abdominal aorta and its branches (AAB). METHODS: By use of the Healthcare Cost and Utilization Project State Inpatient Database from Florida and California, patients who underwent open revascularization of AAB between 2006 and 2011 were identified. Patients diagnosed with aortic dissection or abdominal aortic aneurysm were excluded to limit the study cohort to include only patients with occlusive etiology. Also excluded were those with a pre-existing diagnosis of atrial fibrillation and those who underwent thoracic aortic repair and peripheral artery revascularization procedures. Multivariable logistic and linear regression analyses with treatment effects were conducted to analyze the association between TPAF and length of stay (LOS); the mortality rates at index admission, 1 month, and 1 year; and the readmission rates at 1 month and 1 year (adjusted for comorbidities and surgical and demographic factors). A backwards stepwise logistic regression model was built to identify predictors of TPAF. RESULTS: A total of 4462 patients were identified; 3253 underwent aortoiliac/femoral bypasses (72.9%), 1514 endarterectomies of AAB (33.9%), and 288 bypasses of AAB (6.5%). The incidence of TPAF was 2.4% (109 patients). Multivariate regression analysis with treatment effects showed that TPAF was associated with significantly increased LOS, mortality, and readmission rates. Factors identified as predictors of TPAF by backwards stepwise logistic regression modeling include electrolyte disorders, increasing age, and Charlson Comorbidity Index (C statistic = .69; accuracy = 58%). CONCLUSIONS: TPAF after revascularization of AAB is associated with increased LOS, inpatient mortality, 1-year mortality, and hospital readmissions. Strategies to identify patients at risk for development of TPAF and implementation of appropriate prophylactic measures may improve surgical outcomes and reduce cost of care.

"Take the Volume Pledge" may result in disparity in access to care.

BACKGROUND: "Take the Volume Pledge" proposes restricting pancreatectomies to hospitals that perform ≥20 per year. Our purpose was to identify those factors that characterize patients at risk for loss of access to pancreatic cancer care with enforcement of volume standards. METHODS: Using the Healthcare Cost and Utilization Project State Inpatient Database from Florida, we identified patients who underwent pancreatectomy for pancreatic malignancy from 2007-2011. American Hospital Association and United States Census Bureau data were linked to patient-level data. High-volume hospitals were defined as performing ≥20 pancreatic resections per year. Univariable and multivariable statistics compared patient characteristics and utilization of high-volume hospitals. Classification and Regression Tree modeling was used to predict patients at risk for losing access to care. RESULTS: Our study included 1,663 patients. Five high-volume hospitals were identified, and they treated 1,056 (63.5%) patients. Patients residing far from high-volume hospitals, in areas with the highest population density, non-Caucasian ethnicity, and greater income had decreased odds of obtaining care at high-volume hospitals. Using these factors, we developed a Classification and Regression Tree-based predictive tool to identify these patients. CONCLUSION: Implementation of "Take the Volume Pledge" is an important step toward improving pancreatectomy outcomes; however, policymakers must consider the potential impact on limiting access and possible health disparities that may arise.

Microfluidics platform for glass capillaries and its application in droplet and nanoparticle fabrication.

The accessibility to microfluidics of a broader scientific community is often limited by the costly and complex manufacture of the chips. In this respect, we present a simple and reusable platform for the flexible and easy assembly of glass capillaries to create a microfluidics chip within minutes, with excellent chemical compatibility and durability, and without the need of using specialized infrastructure. To demonstrate the application of the proposed platform, we have used it to produce microparticles by the double emulsion approach, nanoparticles by nanoprecipitation, and screened the nanoparticles' size and polydispersity obtained upon modification of various parameters.

Impact of Post-Hospital Syndrome on Outcomes Following Elective, Ambulatory Surgery.

OBJECTIVE: The aim of this study was to investigate whether post-hospital syndrome (PHS) places patients undergoing elective hernia repair at increased risk for adverse postoperative events. SUMMARY OF BACKGROUND DATA: PHS is a transient period of health vulnerability following inpatient hospitalization for acute illness. PHS has been well studied in nonsurgical populations, but its effect on surgical outcomes is unclear. METHODS: State-specific datasets for California in 2011 available through the Healthcare Cost and Utilization Project (HCUP) were linked. Patients older than 18 years who underwent elective hernia repair were included. The primary exposure variable was PHS, defined as any inpatient admission within 90 days of an elective hernia repair performed in an ambulatory surgery center. The primary outcome was an adverse event, defined as any unplanned emergency department visit or inpatient admission within 30 days postoperatively. Mixed-effects logistic models were used for multivariable analyses. RESULTS: A total of 57,988 patients met inclusion criteria. The 30-day risk-adjusted adverse event rate was significantly higher for PHS patients versus non-PHS patients (11.8% vs 5.8%, P < 0.001). PHS patients were more likely than non-PHS patients to experience postoperative complications (odds ratio 2.2, 95% confidence interval 1.6-3.0). Adverse events attributable to PHS cost an additional $63,533.46 per 100 cases in California. The risk of adverse events due to PHS remained elevated throughout the 90-day window between hospitalization and surgery. CONCLUSIONS: Patients hospitalized within 90 days of an elective surgery are at increased risk of adverse events postoperatively. The impact of PHS on outcomes is independent of baseline patient characteristics, medical comorbidities, quality of center performing the surgery, and reason for hospitalization before elective surgery. Adverse events owing to PHS are costly and represent a quality improvement target.

Perioperative support, not volume, is necessary to optimize outcomes in surgical management of necrotizing enterocolitis.

BACKGROUND: This study examines the relationship between hospital volume of surgical cases for necrotizing enterocolitis (NEC) and patient outcomes. METHODS: A retrospective cross-sectional review was performed using the HCUP SID for California from 2007 to 2011. Patients with NEC who underwent surgery were identified using ICD-9CM codes. Risk-adjusted models were constructed with mixed-effects logistic regression using patient and demographic covariates. RESULTS: 23 hospitals with 618 patients undergoing NEC-related surgical intervention were included. Overall mortality rate was 22.5%. There were no significant differences in the number of NICU beds (p = 0.135) or NICU intensivists (p = 0.469) between high and low volume hospitals. Following risk adjustment, no difference in mortality rate was observed between high and low volume hospitals respectively (24.0% vs. 20.3%, p = 0.555). CONCLUSIONS: Our observation that neonates with NEC treated at low-volume centers have no increased risk of mortality may be explained by similar availability of NICU and intensivists resources across hospitals.

Characterizing the role of a high-volume cancer resection ecosystem on low-volume, high-quality surgical care.

BACKGROUND: Our objective was to determine the hospital resources required for low-volume, high-quality care at high-volume cancer resection centers. METHODS: Patients who underwent esophageal, pancreatic, and rectal resection for malignancy were identified using Healthcare Cost and Utilization Project State Inpatient Database (Florida and California) between 2007 and 2011. Annual case volume by procedure was used to identify high- and low-volume centers. Hospital data were obtained from the American Hospital Association Annual Survey Database. Procedure risk-adjusted mortality was calculated for each hospital using multilevel, mixed-effects models. RESULTS: A total of 24,784 patients from 302 hospitals met the inclusion criteria. Of these, 13 hospitals were classified as having a high-volume, oncologic resection ecosystem by being a high-volume hospital for ≥2 studied procedures. A total of 11 of 31 studied hospital factors were strongly associated with hospitals that performed a high volume of cancer resections and were used to develop the High Volume Ecosystem for Oncologic Resections (HIVE-OR) score. At low-volume centers, increasing HIVE-OR score resulted in decreased mortality for rectal cancer resection (P = .038). HIVE-OR was not related to risk-adjusted mortality for esophagectomy (P = .421) or pancreatectomy (P = .413) at low-volume centers. CONCLUSION: Our study found that in some settings, low-volume, high-quality cancer surgical care can be explained by having a high-volume ecosystem.

pH-Switch Nanoprecipitation of Polymeric Nanoparticles for Multimodal Cancer Targeting and Intracellular Triggered Delivery of Doxorubicin.

Theranostic nanoparticles are emerging as potent tools for noninvasive diagnosis, treatment, and monitoring of solid tumors. Herein, an advanced targeted and multistimuli responsive theranostic platform is presented for the intracellular triggered delivery of doxorubicin. The system consists of a polymeric-drug conjugate solid nanoparticle containing encapsulated superparamagnetic iron oxide nanoparticles (IO@PNP) and decorated with a tumor homing peptide, iRGD. The production of this nanosystem is based on a pH-switch nanoprecipitation method in organic-free solvents, making it ideal for biomedical applications. The nanosystem shows sufficient magnetization saturation for magnetically guided therapy along with reduced cytotoxicity and hemolytic effects. IO@PNP are largely internalized by endothelial and metastatic cancer cells and iRGD decorated IO@PNP moderately enhance their internalization into endothelial cells, while no enhancement is found for the metastatic cancer cells. Poly(ethylene glycol)-block-poly(histidine) with pH-responsive and proton-sponge properties promotes prompt lysosomal escape once the nanoparticles are endocyted. In addition, the polymer-doxorubicin conjugate solid nanoparticles show both intracellular lysosomal escape and efficient translocation of doxorubicin to the nuclei of the cells via cleavage of the amide bond. Overall, IO@PNP-doxorubicin and the iRGD decorated counterpart demonstrate to enhance the toxicity of doxorubicin in cancer cells by improving the intracellular delivery of the drug carried in the IO@PNP.

Vamos brincar na escolinha inserindo atividades de jogos e brincadeiras em escolas de ensino infantil / Let's play in kindergarten? inserting games and play activities in children's schools

Possibilidades de brincar são escassas na escola, por isto este estudo apresenta um programa realizado em cidade de São Paulo, com 54 professores e aproximadamente 300 crianças de escolas infantis municipais, que incluiu aulas teóricas e práticas, debates, um evento e exposição de painéis. Todas as atividades foram registradas. Verificou-se que as rotinas de tais instituições são rígidas e sem tempo para brincar, mesmo sendo reconhecida a importância do brincar para a criança. Foram oferecidas às crianças oportunidades para brincar com seus pares na classe. No evento, crianças de diferentes idades puderam brincar juntas. O estudo mostrou que há possibilidade de mudar a situação nas escolas infantis aumentando oportunidades para as crianças brincarem.

Opportunities to play are rarely in the school, so this study presents a program that was done in a city of Sao Paulo, with 54 teachers and around 300 children from public Early Schools. The program included theoretical and practical class, discussions, an event and panel expositions. All activities were registered. It was verified that routines of such institutions are rigid and without time to play, although it is recognized to play is important to the children. I was offered to children opportunities to play with their peers in the class. In the event, children from different ages could play together. The study showed there are possibilities to change the situation in early schools increasing children´s opportunities to play.

Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs.

Multifunctional tailorable composite systems, specifically designed for oral dual-delivery of a peptide (glucagon-like peptide-1) and an enzymatic inhibitor (dipeptidyl peptidase 4 (DPP4)), were assembled through the microfluidics technique. Both drugs were coloaded into these systems for a synergistic therapeutic effect. The systems were composed of chitosan and cell-penetrating peptide modified poly(lactide-co-glycolide) and porous silicon nanoparticles as nanomatrices, further encapsulated in an enteric hydroxypropylmethylcellulose acetylsuccinate polymer. The developed multifunctional systems were pH-sensitive, inherited by the enteric polymer, enabling the release of the nanoparticles only in the simulated intestinal conditions. Moreover, the encapsulation into this polymer prevented the degradation of the nanoparticles' modifications. These nanoparticles showed strong and higher interactions with the intestinal cells in comparison with the nonmodified ones. The presence of DPP4 inhibitor enhanced the peptide permeability across intestinal cell monolayers. Overall, this is a promising platform for simultaneously delivering two drugs from a single formulation. Through this approach peptides are expected to increase their bioavailability and efficiency in vivo both by their specific release at the intestinal level and also by the reduced enzymatic activity. The use of this platform, specifically in combination of the two antidiabetic drugs, has clinical potential for the therapy of type 2 diabetes mellitus.

Microfluidic assisted one-step fabrication of porous silicon@acetalated dextran nanocomposites for precisely controlled combination chemotherapy.

An advanced nanocomposite consisting of an encapsulated porous silicon (PSi) nanoparticle and an acid-degradable acetalated dextran (AcDX) matrix (nano-in-nano), was efficiently fabricated by a one-step microfluidic self-assembly approach. The obtained nano-in-nano PSi@AcDX composites showed improved surface smoothness, homogeneous size distribution, and considerably enhanced cytocompatibility. Furthermore, multiple drugs with different physicochemical properties have been simultaneously loaded into the nanocomposites with a ratiometric control. The release kinetics of all the payloads was predominantly controlled by the decomposition rate of the outer AcDX matrix. To facilitate the intracellular drug delivery, a nona-arginine cell-penetrating peptide (CPP) was chemically conjugated onto the surface of the nanocomposites by oxime click chemistry. Taking advantage of the significantly improved cell uptake, the proliferation of two breast cancer cell lines was markedly inhibited by the CPP-functionalized multidrug-loaded nanocomposites. Overall, this nano-in-nano PSi@polymer composite prepared by the microfluidic self-assembly approach is a universal platform for nanoparticles encapsulation and precisely controlled combination chemotherapy.

Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.

A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties.