The dorsal muscle group area at the T12 vertebral level as a risk factor for tolerability of nintedanib in patients with idiopathic pulmonary fibrosis or other progressive fibrosing interstitial lung diseases.

Nintedanib, a multi-intracellular tyrosine kinase inhibitor, reduces progression of idiopathic pulmonary fibrosis (IPF) and has been approved to use in other progressive fibrosing interstitial lung diseases (ILD) recently. However, the factors that affect the discontinuation of treatment due to adverse events is uncertain. The dorsal muscle group area at the T12 vertebral level (T12DMA) assessed on computed tomography (CT) images has been reported to be associated with mortality in chronic obstructive pulmonary disease (COPD) and other diseases. The relationship between T12DMA and the discontinuation of nintedanib remains unclear. METHODS: 39 patients with IPF or other progressive fibrosing ILDs who started nintedanib at a regular dose (300 mg/day) were enrolled. We compared the characteristics between patients who stopped nintedanib at a regular dose before 6 months and/or continue to take nintedanib at a low dose (150 mg/day) and patients who were still taking nintedanib at a regular dose over 6 months. This study retrospectively investigated clinical parameters including T12DMA index (T12DMA/height2) to evaluate whether these parameters might serve as risk factor for the tolerability of nintedanib in patients with IPF and other progressive fibrosing ILDs. RESULTS: Discontinuation or dose reductions of nintedanib due to adverse events were observed in 14 (35.8%) patients. A multiple logistic regression model showed T12DMA index to be the only significant risk factor for predicting for the early termination of nintedanib (odd rate, 0.549; 95% confidence interval, 0.327-0.922; P = .023). CONCLUSIONS: This study revealed that T12DMA index was a risk factor for the early termination of nintedanib. The initial dose of nintedanib adjusted to the differences in skeletal muscle mass and careful management of adverse events may contribute to the longer nintedanib treatment, which would lead to a better clinical outcome.

Docosahexaenoic acid contributes to increased CaMKII protein expression and a tendency to increase nNOS protein expression in differentiated NG108-15 cells.

Docosahexaenoic acid (DHA; 22:6n-3), an n-3 polyunsaturated fatty acid, has various important roles in brain functions. Nitric oxide (NO) produced by neuronal NO synthase (nNOS) and Ca2+/calmodulindependent protein kinase II (CaMKII) is also involved in brain functions. We investigated the influence of DHA on nNOS and CaMKII protein expression in differentiated NG108-15 cells. NG108-15 cells were seeded in 12-well plates, and after 24 h, the medium was replaced with Dulbecco's modified Eagle's medium containing 1% fetal bovine serum, 0.2 mM dibutyryl cyclic adenosine monophosphate and 100 nM dexamethasone as differentiation-inducing medium. When cells were cultured in differentiation-inducing medium, neurite-like outgrowths were observed on days 5 and 6. However, no significant difference in morphology was observed in cells with or without DHA treatment. With or without DHA addition, nNOS protein expression was increased on days 5 and 6 compared with day 0. This increase tended to be enhanced by DHA. CaMKII protein expression did not change after differentiation without DHA, but was significantly increased on day 6 compared with day 0 with DHA addition. These data indicate that DHA is involved in brain functions by regulating CaMKII and nNOS protein expression.

Translational study for stereotactic body radiotherapy against non-small cell lung cancer, including oligometastases, considering cancer stem-like cells enable predicting clinical outcome from in vitro data.

BACKGROUND: Curative effects of stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) have been evaluated using various biophysical models. Because such model parameters are empirically determined based on clinical experience, there is a large gap between in vitro and clinical studies. In this study, considering the heterogeneous cell population, we performed a translational study to realize the possible linkage based on a modeling approach. METHODS: We modeled cell-killing and tumor control probability (TCP) considering two populations: progeny and cancer stem-like cells. The model parameters were determined from in vitro survival data of A549 and EBC-1 cells. Based on the cellular parameters, we predicted TCP and compared it with the corresponding clinical data from 553 patients collected at Hirosaki University Hospital. RESULTS: Using an all-in-one developed model, the so-called integrated microdosimetric-kinetic (IMK) model, we successfully reproduced both in vitro survival after acute irradiation and the 3-year TCP with various fractionation schemes (6-10 Gy per fraction). From the conventional prediction without considering cancer stem cells (CSCs), this study revealed that radioresistant CSCs play a key role in the linkage between in vitro and clinical outcomes. CONCLUSIONS: This modeling study provides a possible generalized biophysical model that enables precise estimation of SBRT worldwide.

A case of metastatic endobronchial tumor from uterine leiomyosarcoma.

A 54-year-old woman presented with persistent productive cough, found to have an endobronchial tumor which obstructed the left upper lobe bronchus. Histopathological examination of a transbronchial biopsy of the endobronchial tumor suggested leiomyosarcoma. A positron emission tomography (PET)-CT revealed uterus tumor with moderate uptake of 18F-fluorodeoxyglucose, suggesting uterine malignancies. From the results of histological findings of the resected uterus and the biopsied bronchial specimen, she was diagnosed with uterine leiomyosarcoma and endobronchial metastasis. The systematic use of PET-CT could be useful for patients presenting with tumors that cause endobronchial metastasis of leiomyosarcomas.

Identification of novel prognostic factors focusing on clinical outcomes in patients with non-small cell lung cancer after stereotactic body radiotherapy.

Stereotactic body radiotherapy (SBRT) has attracted extensive attention as an effective treatment for patients with early-stage non-small cell lung cancer. However, the factors affecting prognosis after SBRT have not been fully elucidated. The aim of the present study was to investigate the prognostic factors associated with overall survival (OS) and local control (LC) after SBRT. Between March 2003 and March 2020, 497 patients with primary or oligo-metastatic lung cancer who underwent SBRT treatment were retrospectively reviewed. Univariate analysis was performed against various factors related to patient and tumor characteristics using Kaplan-Meier method. Furthermore, the factors with statistically significant differences identified via univariate analysis underwent a stratified Cox proportional hazard regression analysis. The median follow-up period for all patients was 26.17 months (range, 0.36-194.37), and the 5-year OS and LC rates were 66.3 and 86.0%, respectively. Multivariate analysis showed that surfactant protein-D (SP-D), tumor CT values (TCTV) and iodine density values (IDV) were independent prognostic factors for OS, and histology, TCTV and IDV were for LC. Although histology was not selected as a prognostic factor related to OS, it was indicated that patients with squamous cell carcinoma were associated with the SP-D high group compared with the SP-D normal group. In addition, TCTV was correlated to water density values, which tended to decrease with increasing IDV. From these findings, SP-D and TCTV were identified as potential new candidate prognostic factors after SBRT, and it is possible that combining SP-D and histology, and TCTV and IDV may improve the accuracy of prognostic prediction.

Retrolabyrinthine transsigmoid approach to complex parabrainstem tumors in the posterior fossa.

OBJECTIVE: The surgical management of large and complex tumors of the posterior fossa poses a formidable challenge in neurosurgery. The standard retrosigmoid craniotomy approach has been performed at most neurosurgical centers; however, the retrosigmoid approach may not provide enough working space without significant retraction of the cerebellum. The transsigmoid approach provides wider and shallower surgical fields; however, there have been few clinical and no cadaveric studies on its usefulness. In the present study, the authors describe the transsigmoid approach in clinical cases and cadaveric specimens. METHODS: For the clinical study, the authors retrospectively reviewed the medical records and operative charts of patients who had been surgically treated for parabrainstem tumors using the transsigmoid approach between 1997 and 2019. They analyzed patient demographic and clinical data, as well as surgical and clinical outcomes. In the cadaveric study, they compared the surgical views obtained in different approaches (retrosigmoid, presigmoid, retrolabyrinthine, and transsigmoid) and measured the sigmoid sinus width at the level of the endolymphatic sac and the distance between the anterior edge of the sigmoid sinus and the endolymphatic sac on 35 sides in 19 cadaveric specimens. RESULTS: A total of 21 patients (6 males and 15 females) with a mean age of 42.2 (range 15-67) years were included in the clinical study. Eleven patients had meningioma, 7 had vestibular schwannoma, 2 had hemangioblastoma, and 1 had epidermoid cyst. Gross-total, near-total, and subtotal removal were achieved in 7 (33.3%), 3 (14.3%), and 11 (52.4%) patients, respectively. In the cadaveric study, 19 cadaveric specimens were used. The sigmoid sinus was cut in the middle, and the incision was extended from the retrosigmoid to the presigmoid dura. The dura was then retracted upward and downward like opening a door. The results indicated that this technique can widen the operative field anteriorly by approximately 2 cm as compared to the retrosigmoid approach and provides a better view anterior to the brainstem. CONCLUSIONS: The transsigmoid approach is useful for complex parabrainstem tumors in the posterior fossa because it provides a wider and shallower operative view with less retraction of the cerebellum. This enables safer tumor removal with less damage to important structures in the posterior fossa, resulting in better operative and clinical outcomes.

Revalidation of inferior petrosal sinus sampling: the latest results from a single-center experience.

Cushing's disease (CD), which manifests as excess cortisol secretion, is caused by adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas. Such adenomas are occasionally difficult to identify on magnetic resonance imaging (MRI), and thorough endocrinological examination may be required to detect them. Inferior petrosal sinus (IPS) sampling (IPSS) has been the gold standard test for distinguishing CD from ectopic ACTH syndrome (EAS). However, IPSS is an invasive procedure, and proper catheterization is occasionally challenging due to anatomical variations. Thus, there have been ongoing debates regarding the necessity of this procedure. Here, we present our recent IPSS data derived from the analysis of 65 patients who were referred to us for possible CD between April 2018 and December 2020 after undergoing meticulous endocrinological testing. Even with detailed MRI, no obvious lesions were identified in 19 patients. IPSS performed on these 19 individuals identified an IPS-to-peripheral ACTH gradient in 15 of them. The four patients who lacked this gradient were subjected to a classical algorithm using concurrently measured prolactin levels, the results of which were consistent with their ultimately confirmed diagnoses: two true-positive and two true-negative diagnoses. These findings support the validity of the algorithm and demonstrate that the prolactin-adjusted IPS-to-peripheral ACTH ratio can improve the differentiation between CD and EAS. We had no false-negative results, but three patients were false-positive. Consequently, those three patients in which no apparent tumor was clarified during surgery could not have any endocrinological improvement postoperatively.

Exhaled nitric oxide: A biomarker for chronic obstructive pulmonary disease.

The fractional concentration of exhaled nitric oxide (FeNO) is recognized as a biomarker of type 2 inflammation in asthma, which is related to airway eosinophilia. We conducted a prospective observational study in a cohort of Japanese patients with chronic obstructive pulmonary disease (COPD) to evaluate the relationship between FeNO and clinical features and patient outcomes over a 3-year period. Participants were categorized into two groups based on FeNO levels (high and low), and the clinical features and outcomes were compared between the groups. Patients with high FeNO levels showed features of asthma and eosinophilic inflammation compared to those with low levels. However, high FeNO levels were not associated with worse outcomes (exacerbations, hospital admissions, all-cause and disease-specific mortality) compared to low levels. These results provide evidence that baseline FeNO is related to eosinophilic inflammation; however, is not a predictor of future exacerbations or prognosis in patients with stable COPD.

Treatment of an anterior cerebral artery pseudoaneurysm secondary to a transsphenoidal surgery using stent-assisted coiling.

BACKGROUND: Injury of the internal carotid artery (ICA) during transsphenoidal surgery (TSS) is a rare but critical complication. There are several reports on endovascular treatment of ICA injury during TSS. With the recent flourishing of extended TSS, injuries to the distal arteries such as the anterior cerebral artery (ACA) are more likely to occur. CASE DESCRIPTION: In the present case, we report a pseudoaneurysm of the right ACA due to injury during extended TSS for aggressive prolactinoma. Due to the absence of collateral vessels, the pseudoaneurysm had to be obliterated while preserving the parent artery. Hence, we decided to treat the pseudoaneurysm using stent-assisted coiling (SAC). The pseudoaneurysm was completely obliterated and he was discharged without any complications. CONCLUSION: To the best of our knowledge, this is the first case in which an ACA pseudoaneurysm caused by injury during the TSS was treated with SAC and the parent artery was preserved.

Hemostasis through Extended Transsphenoidal Route for Subarachnoid Hemorrhage after Conventional Transsphenoidal Surgery for a Pituitary Adenoma.

This report describes a 49-year-old male patient who presented with a pituitary adenoma extending to the suprasellar region. Subarachnoid hemorrhage (SAH) occurred after conventional transnasal transsphenoidal surgery for a non-functioning pituitary adenoma despite no suprasellar arachnoid membrane breakdown. Through extended transsphenoidal route, the suprasellar hematoma was removed and bleeding from a small vessel thought to be the branch of left superior hypophyseal artery was successfully controlled. Indeed, several case reports regarding this rare complication have been published, but the mechanism of SAH has never been identified and the prognosis was poor in most cases. This report illustrates the origin and mechanism of the bleeding clearly using the intraoperative video. This case suggests that immediate therapeutic intervention is necessary and extended transnasal transsphenoidal repeat surgery is useful for an appropriate hemostasis and removal of hematoma located in the suprasellar region.

Clinical Characteristics and Outcomes of Patients with Asthma-COPD Overlap in Japanese Patients with COPD.

Purpose: Asthma-COPD overlap (ACO) has been reported as an association with a lower quality of life, frequent exacerbations, and higher mortality than those with COPD alone. However, clinical characteristics and outcomes of ACO remain controversial. Patients and Methods: We conducted a prospective observational study analyzing data of patients with stable COPD enrolled from the Ishinomaki COPD Network Registry. Patients with features of asthma who had a history of respiratory symptoms that vary over time and intensity, together with documented variable expiratory airflow limitation, were identified, and then defined as having ACO. The characteristics, frequency of exacerbations, and mortality during the 3-year follow-up were compared between patients with ACO and patients with COPD alone. Results: Among 387 patients with COPD, 41 (10.6%) were identified as having ACO. Patients with ACO tended to be younger, have higher BMI, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids. Inflammatory biomarkers including fractional exhaled nitric oxide, blood eosinophil count, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were significantly higher in patients with ACO than in those with COPD alone. Lung function, mMRC score, CAT score, and comorbidity index were not different between the groups. The annual rate of all exacerbations and severe exacerbations required hospital admission were not different between ACO and COPD alone (0.20 vs 0.14, 0.12 vs 0.10, events per person, respectively). Mortality was significantly higher in patients with COPD alone compared with those with ACO during the study period (P=0.037). Conclusion: The results of our study indicate that ACO is not associated with poor clinical features nor outcomes in an outpatient COPD cohort receiving appropriate treatment.

Clinical characteristics of Japanese patients with chronic obstructive pulmonary disease (COPD) with comorbid interstitial lung abnormalities: A cross-sectional study.

Smoking-related interstitial lung abnormalities are different from specific forms of fibrosing lung disease which might be associated with poor prognoses. Chronic obstructive pulmonary disease with comorbid interstitial lung abnormalities and that with pulmonary fibrosis are considered different diseases; however, they could share a common spectrum. We aimed to evaluate the clinical characteristics of Japanese patients with chronic obstructive pulmonary disease and comorbid interstitial lung abnormalities. In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry. We evaluated the clinical characteristics of patients with chronic obstructive pulmonary disease with and without comorbid interstitial lung abnormalities by comparing the annualized rate of chronic obstructive pulmonary disease exacerbations per patient during the observational period. Among 463 patients with chronic obstructive pulmonary disease, 30 (6.5%) developed new interstitial lung abnormalities during the observational period. After 1-to-3 propensity score matching, we found that the annualized rate of chronic obstructive pulmonary disease exacerbations per patient during the observational period was 0.06 and 0.23 per year in the interstitial lung abnormality and control groups, respectively (P = 0.043). Our findings indicate slow progression of interstitial lung abnormality lesions in patients with pre-existing chronic obstructive pulmonary disease. Further, interstitial lung abnormality development did not significantly influence on chronic obstructive pulmonary disease exacerbation. We speculate that post-chronic obstructive pulmonary disease interstitial lung abnormalities might involve smoking-related interstitial fibrosis, which is different from specific forms of fibrosing lung disease associated with poor prognoses.

Body Movement Synchrony Predicts Degrees of Information Exchange in a Natural Conversation.

Human interaction has two principle functions: building and maintaining relationships with others and exchanging information. The function of building and maintaining relationships with others relates to interpersonal coordination; this behavior pattern is expected to predict the outcome of social relationships, such as between therapists and patients. It is unclear, however, whether the exchange of information is associated with interpersonal coordination. In the present study, we tested a hypothesis of whether body movement synchrony occurs in a natural conversation and whether this synchrony has a positive correlation with the degree of information exchange. Fifty participants were engaged in a conversation task; each had different roles in the conversation. We measured their body movements during this conversation using an optical motion capture system. Similar to methods that can be found in previous research, we calculated body movements and quantified their synchrony applying the methods previously reported that automatically quantified their body movements. Moreover, we determined the participants' degree of information exchange concerning the conversation using a questionnaire. We observed that the body movement synchrony of pairs who talked with each other was significantly higher than that of pairs who did not talk with each other, and that this synchrony was positively associated with the degree of information exchange. These results suggest that body movement synchrony predicted information exchange.

Trapa bispinosa Roxb. and lutein ameliorate cataract in type 1 diabetic rats.

Trapa bispinosa Roxb. is an annual aquatic grass of the citrus family. Although its hot water extract displays antioxidative activity in vitro, little is known about its biological effectiveness. In the present study, we evaluated the extract's inhibitory effect on diabetic cataractogenesis and formation of advanced glycation end-product. Lutein, which is beneficial for eye diseases, was administered concurrently. For short-term administration, Trapa bispinosa Roxb. hot water extract and/or lutein were administered to type 1 diabetic rats. N ɛ-(carboxymethyl)lysine and N ɛ-(carboxyethyl)lysine were quantified in serum using mass spectrometry. The long-term administration study was similar to the short-term, except that the dosages were lower. In the short-term study, co-administration of the extract and lutein inhibited N ɛ-(carboxymethyl)lysine and N ɛ-(carboxyethyl)lysine in serum. However, in the long-term study, only lutein inhibited N ɛ-(carboxymethyl)lysine and N ɛ-(carboxyethyl)lysine in serum. These results suggest that lutein exerts its long-term effect regardless of the concentration administered, while the extract exerts its effect when its concentration is increased. Relative to the consumption of the control diet, oral intake of the combination of the extract and lutein significantly inhibited the progression of cataractogenesis in the lens of diabetic rats, even at low doses, and the combination was more effective than individual treatments.

Preauricular retromandibular trans tympanic plate and styloid process keyhole approach to parapharyngeal lesions: a laboratory study.

BACKGROUND: The surgical removal of the infratemporal parapharyngeal lesions (IPL) is challenging due to its anatomical complexity. Previous surgical approaches have often been too invasive and necessitated sacrifice of normal function and anatomical structures, particularly in the retromandibular nerve region. Therefore, we sought to identify an approach corridor to this area that requires less sacrifice and report an innovative approach through a retromandibular fossa route to the IPL. METHODS: Five cadaveric specimens were dissected bilaterally with a trans-tympanic plate and styloid process approach. These specimens were investigated microanatomically and morphometrically to examine the extent of the approach in the parapharyngeal space. The clinical application of this approach was compared to previous approaches to the IPL used in our clinical series of 20 cases. RESULTS: Using this novel approach, the inferior alveolar nerve was identified in all specimens, while the chorda tympani and lingual nerve were identified in 6 (60%) and 4 (40%) dissections, respectively. In all specimens, the petrous portion of the internal carotid artery and the exit of the lower cranial nerve were identified. The average length of the exposed lower cranial nerves was 16.6 ± 3.8 mm (range: 11-25 mm). CONCLUSIONS: The described approach is feasible for accessing the IPL at the retromandibular nerve and is less invasive than conventionally used approaches.

Clinical characteristics and outcomes in Japanese patients with COPD according to the 2017 GOLD classification: the Ishinomaki COPD Network Registry.

PURPOSE: The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations. The GOLD 2017 proposes a new classification whereby patients are grouped as A-D according to their symptoms and history of exacerbations. However, the clinical characteristics and outcomes in these patients are not well documented. PATIENTS AND METHODS: In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry. All patients with stable COPD were classified into the four groups defined by GOLD 2017. The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups. RESULTS: Four hundred and one patients with stable COPD were identified. There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D. Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A. Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period. Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B). Mortality was not different between the high-risk and low-risk groups. CONCLUSION: The results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality.

The Novel Pathogenesis of Retinopathy Mediated by Multiple RTK Signals is Uncovered in Newly Developed Mouse Model.

Pericyte desorption from retinal blood vessels and subsequent vascular abnormalities are the pathogenesis of diabetic retinopathy (DR). Although the involvement of abnormal signals including platelet-derived growth factor receptor-ß (PDGFRß) and vascular endothelial growth factor-A (VEGF-A) have been hypothesized in DR, the mechanisms that underlie this processes are largely unknown. Here, novel retinopathy mouse model (N-PRß-KO) was developed with conditional Pdgfrb gene deletion by Nestin promoter-driven Cre recombinase (Nestin-Cre) that consistently reproduced through early non-proliferative to late proliferative DR pathologies. Depletion of Nestin-Cre-sensitive PDGFRß+NG2+αSMA- pericytes suppressed pericyte-coverages and induced severe vascular lesion and hemorrhage. Nestin-Cre-insensitive PDGFRß+NG2+αSMA+ pericytes detached from the vascular wall, and subsequently changed into myofibroblasts in proliferative membrane to cause retinal traction. PDGFRα+ astrogliosis was seen in degenerated retina. Expressions of placental growth factor (PlGF), VEGF-A and PDGF-BB were significantly increased in the retina of N-PRß-KO. PDGF-BB may contribute to the pericyte-fibroblast transition and glial scar formation. Since VEGFR1 signal blockade significantly ameliorated the vascular phenotype in N-PRß-KO mice, the augmented VEGFR1 signal by PlGF and VEGF-A was indicated to mediate vascular lesions. In addition to PDGF-BB, PlGF and VEGF-A with their intracellular signals may be the relevant therapeutic targets to protect eyes from DR.

A Dual Alkylated Peptide-ligand Enhances Affinity to Human Serum Albumin.

Therapeutic peptides and diagnostic agents with their molecular size below the renal clearance threshold suffer from short blood circulation time. Here, we report a novel design of peptide-based ligand with a strong binding affinity to human serum albumin (HSA), which can be used as a tag to extend the blood circulation of small-size molecules. We designed ligands with dual alkyl groups connected with a negatively charged spacer. The ligands showed both higher binding affinity to HSA and a higher retention in mice blood than that of a single alkylated peptide.

Ligand-Mediated Coating of Liposomes with Human Serum Albumin.

Coating liposome surfaces with human serum albumin (HSA) can improve the colloidal stability and prevent opsonization. HSA coating via specific binding with alkyl ligands is promising because although the ligand-mediated coating is relatively stable it can spontaneously exchange with fresh HSA. However, to achieve surface coating with HSA, multiple hydrophobic ligands must be exposed to an aqueous medium prior to binding with HSA. This presents a challenge, as hydrophobic ligands tend to be buried in the liposomal membrane. Here we present the first HSA modification of liposome surfaces via alkyl ligands. We found that a relatively short alkyl ligand, or a long alkyl ligand with a terminal carboxylate, could be exposed on the liposome surface without causing aggregation of the liposomes and these ligands could subsequently bind HSA. The resulting HSA-coated liposomes were as inert as conventional PEGylated liposomes in terms of macrophage recognition.

Modification of ligands for serum albumin on polyethyleneimine to stabilize polyplexes in gene delivery.

In this work, we have developed a new technique to stabilize a ternary complex composed of plasmid DNA, a linear polyethyleneimine (LPEI) and serum albumin. A stearoyl group was conjugated to LPEI as a specific ligand for serum albumin. The resultant ternary complex has excellent stability in physiological saline conditions, maintaining its initial diameter and preventing aggregation of red blood cells. The ternary complex has equivalent transfection ability to and significantly lower cytotoxicity than unmodified LPEI. Therefore, the ternary complex is potentially useful as a new gene carrier, possessing high blood stability.