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1.
Pharmaceutics ; 16(3)2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38543250

ABSTRACT

In the field of preparing cosmetic formulations, recent advances recommend the usage of excipients derived from biocompatible materials. In this context, the present study aimed to prepare and characterize the curcumin-loaded Pickering emulsion for possible applications in cosmetic formulation. The coconut oil which is often the component of skin care formulations is used as the oily phase. Curcumin, which is well known for absorbing solar radiation, is expected to work synergistically with coconut oil towards improving the sun protection factor (SPF) of the formulation. Additionally, curcumin can also protect the intracellular components through its well-known antioxidant mechanisms. The Pickering emulsion of coconut oil into water was prepared using the composite colloidal particles derived from ß-carboxymethyl chitosan (CMC) and Gelatin-A (GA) as the emulsifying agent. The reaction conditions in terms of the weight ratios of CMC and GA, the pH of the reaction medium, the oil volume fraction, and the homogenization speed were optimized to obtain the most stable Pickering emulsion. The obtained systems were physico-chemically characterized by dynamic light scattering, zeta potential, optical microscopy, and rheometric measurements. The final CMC-GA-stabilized emulsion demonstrated an oil droplet size of 100 µm and a SPFspectrophotometric (290-320 nm) value of 8.5 at a curcumin loading of 4 mg/mL. Additionally, the final formulation facilitated the uptake of curcumin into fibroblast (WI26) cells under in vitro conditions. Together, the investigation demonstrates a bio-inspired approach to prepare a curcumin-loaded green Pickering emulsion using biocompatible pharmaceutical grade excipients, which may find utility in cosmetic applications.

2.
Toxicol Appl Pharmacol ; 482: 116792, 2024 01.
Article in English | MEDLINE | ID: mdl-38142783

ABSTRACT

Radiotherapy is a common modality for cancer treatment. However, it is often associated with normal tissue toxicity in 20-80% of the patients. Radioprotectors can improve the outcome of radiotherapy by selectively protecting normal cells against radiation toxicity. In the present study, compound libraries containing 54 kinase inhibitors and 80 FDA-approved drugs were screened for radioprotection of lymphocytes using high throughput cell analysis. A second-generation FDA-approved kinase inhibitor, bosutinib, was identified as a potential radioprotector for normal cells. The radioprotective efficacy of bosutinib was evinced from a reduction in radiation induced DNA damage, caspase-3 activation, DNA fragmentation and apoptosis. Oral administration of bosutinib protected mice against whole body irradiation (WBI) induced morbidity and mortality. Bosutinib also reduced radiation induced bone-marrow aplasia and hematopoietic damage in mice exposed to 4 Gy and 6 Gy dose of WBI. Mechanistic studies revealed that the radioprotective action of bosutinib involved interaction with cellular thiols and modulation of JNK pathway. The addition of glutathione and N-acetyl cysteine significantly reduced the radioprotective efficacy of bosutinib. Moreover, bosutinib did not protect cancer cells against radiation induced toxicity. On the contrary, bosutinib per se exhibited anticancer activity against human cancer cell lines. The results highlight possible use of bosutinib as a repurposable radioprotective agent for mitigation of radiation toxicity in cancer patients undergoing radiotherapy.


Subject(s)
Aniline Compounds , Antineoplastic Agents , Drug Repositioning , Nitriles , Quinolines , Radiation Injuries , Radiation-Protective Agents , Animals , Humans , Mice , Aniline Compounds/pharmacology , Aniline Compounds/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , DNA Damage , MAP Kinase Signaling System , Nitriles/pharmacology , Nitriles/therapeutic use , Quinolines/pharmacology , Quinolines/therapeutic use , Radiation Injuries/prevention & control , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/therapeutic use
3.
JAMA Netw Open ; 6(9): e2334889, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37733345

ABSTRACT

Importance: Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes. Objective: To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age. Design, Setting, and Participants: This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022. Interventions: Near-infrared spectroscopy monitoring of Csat and Msat. Main Outcomes and Measures: Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score <85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment. Results: A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower-hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher-hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs -0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03). Conclusions and Relevance: In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia. Trial Registration: ClinicalTrials.gov Identifier: NCT01702805.


Subject(s)
Infant, Premature , Spectroscopy, Near-Infrared , Infant, Newborn , Child , Infant , Humans , Male , Adult , Female , Birth Weight , Blood Transfusion , Gestational Age
4.
J Pediatr ; 263: 113638, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37517646

ABSTRACT

OBJECTIVE: To characterize phosphatidylcholine (PC) molecular species in serial gastric aspirates as biomarkers for lung maturity, delivery of aerosolized surfactant (AS), and need for intubation. METHODS: In a phase II clinical trial of aerosolized surfactant in preterm neonates with respiratory distress syndrome receiving noninvasive ventilation, infants received a maximum of 2 doses of nebulized beractant. Gastric aspirates were collected before and after each dose and were analyzed for PCs using liquid chromatography mass spectrometry. RESULTS: Of 149 infants enrolled, gastric aspirates were obtained before (n = 91) and after (n = 94) dose 1, and before (n = 56) and after (n = 57) dose 2 of nebulized beractant. The mean ± SD values of birthweight, gestational age, and age at collection of baseline gastric aspirate were 1.7 ± 0.6 kg, 31.7 ± 2.8 weeks, and 5.5 ± 1.7 hours, respectively. The most abundant PC in beractant and gastric aspirates was PC(16:0/16:0). Advancing gestational age and number of antenatal corticosteroid doses predicted increased gastric aspirate PC(16:0/16:0), whereas maternal diabetes predicted a decrease. Several PCs increased significantly (P < .05) after nebulized beractant, consistent with effective aerosol delivery. Infants who received intubation within 72 hours of birth were more likely to have lower PC(16:0/16:0) levels in baseline gastric aspirates compared with those who did not (P = .024). CONCLUSIONS: PC molecular species in gastric aspirates of preterm neonates are potentially novel and precise biomarkers to assess lung maturity, aerosol delivery, and need for endotracheal intubation.


Subject(s)
Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Pregnancy , Infant, Newborn , Infant , Humans , Female , Surface-Active Agents/therapeutic use , Phosphatidylcholines/therapeutic use , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome, Newborn/drug therapy , Lipoproteins , Biomarkers , Respiratory Aerosols and Droplets
5.
Pediatr Pulmonol ; 58(7): 1982-1992, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37098830

ABSTRACT

BACKGROUND AND OBJECTIVES: Bronchopulmonary dysplasia (BPD) is a serious complication of preterm birth, resulting in significant morbidity and mortality. Recent studies have suggested that microRNA (miRNA) dysregulation is involved in the pathogenesis of BPD and may serve as biomarkers for early detection. We conducted a directed search for dysregulated miRNAs in lung and heart autopsy samples of infants with histologic BPD. METHODS: We used archived lung and heart samples from BPD (13 lung, 6 heart) and control (24 lung, 5 heart) subjects. To measure miRNA expression, RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue specimens then reverse-transcribed, labeled, and hybridized to miRNA microarrays. The microarrays were scanned, and data were quantile normalized. Statistical analysis with a moderated t-test and control of the false discovery rate (5%) was used to compare normalized miRNA expression values between clinical categories. RESULTS: With our set of 48 samples, 43 miRNAs had a significant difference in expression comparing BPD to non-BPD controls. Among the most statistically significant miRNAs, miR-378b, miRNA-184, miRNA-3667-5p, miRNA-3976, miRNA-4646-5p, and miRNA-7846-3p were all consistently upregulated in both the heart and lung tissues of BPD subjects. The cellular pathway predicted to be most affected by these miRNAs is the Hippo signaling pathway. CONCLUSIONS: This study identifies miRNAs that are similarly dysregulated in postmortem lung and heart samples in subjects with histologic BPD. These miRNAs may contribute to the pathogenesis of BPD, have potential as biomarkers, and may provide insight to novel approaches for diagnosis and treatment.


Subject(s)
Bronchopulmonary Dysplasia , MicroRNAs , Premature Birth , Female , Humans , Infant, Newborn , Infant , MicroRNAs/genetics , MicroRNAs/metabolism , Bronchopulmonary Dysplasia/genetics , Bronchopulmonary Dysplasia/metabolism , Lung/metabolism , Biomarkers/metabolism
6.
Biomater Sci ; 11(4): 1437-1450, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36602012

ABSTRACT

Nitric oxide (NO) plays a pivotal role in the wound healing process and promotes the generation of healthy endothelium. In this work, a simple method has been developed for fabricating a diselenide grafted gelatin gel, which reduces NO donors such as S-nitroso-N-acetylpenicillamine (SNAP) by glutathione peroxidase-like mechanism to produce NO. Briefly, the process involved covalently conjugating 3,3'-diselenodipropionic acid (DSePA) with gelatin via carbodiimide coupling. The resulting gelatin-DSePA conjugate (G-Se-Se-G) demonstrated NO production upon incubation with SNAP and glutathione (GSH) with the flux of 4.8 ± 0.6 nmol cm-2 min-1 and 1.6 ± 0.1 nmol cm-2 min-1 at 10 min and 40 min, respectively. The G-Se-Se-G recovered even after 5 days of incubation with the reaction mixture retaining catalytic activity up to 74%. Subsequently, G-Se-Se-G was suspended (5% w/v) in water with lecithin (6% w/w of gelatin) and F127 (3% w/w of gelatin) to prepare gel through temperature dependant gelation method. The fabricated G-Se-Se-G gel exhibited desirable rheological characteristics and excellent mechanical stability under storage conditions and did not cause any significant toxicity in normal human keratinocytes (HaCaT) and fibroblast cells (WI38) up to 50 µg ml-1 of selenium equivalent. Finally, mice studies confirmed that topically applied G-Se-Se-G gel and SNAP promoted faster epithelization and collagen deposition at the wound site. In conclusion, the development of a biomimetic NO generating gel with sustained activity and biocompatibility was achieved.


Subject(s)
Gelatin , Nitric Oxide , Mice , Humans , Animals , Wound Healing , Nitric Oxide Donors , S-Nitroso-N-Acetylpenicillamine
7.
Pediatrics ; 150(3)2022 09 01.
Article in English | MEDLINE | ID: mdl-36045299

ABSTRACT

Through this policy statement, the American Academy of Pediatrics advocates that all health care insurers adopt consistent medical necessity definitions that reflect the needs of infants, children, adolescents, and young adults (hereafter noted as "children") as a function of developmental, epidemiologic, dependency, demographic, and cost-related factors that change over the pediatric continuum and that differ from adults. Optimally, the scope of benefits defined in health care contracts should address the complete spectrum of health care needs of children and families, but in reality, many plans offer a limited scope of benefits for children. Even if a proposed intervention falls within the scope of benefits or is not specifically excluded from coverage, the health plan may still deny the intervention. In such cases, contractual language may allow an appeal to succeed if the provider demonstrates medical necessity. With the assistance of experienced pediatric physicians and other providers with pediatric expertise, health care payers and agencies should clearly detail the processes that define, evaluate, and determine medical necessity and through which providers may appeal decisions. A basic requirement for any medical necessity process is the consideration of input from the physician(s) caring for a pediatric patient for whom a medical necessity determination is necessary.


Subject(s)
Contracts , Language , Adolescent , Child , Humans , Infant , United States
8.
Early Hum Dev ; 171: 105612, 2022 08.
Article in English | MEDLINE | ID: mdl-35797784

ABSTRACT

Bronchopulmonary Dysplasia (BPD), the commonest complication of prematurity, is defined by treatment with oxygen for ≥28 days. Pulmonary hypertension (PH) often coexists with BPD and is associated with increased mortality. In 42 autopsies, histological changes of BPD and PH were demonstrated in 25 % and 65 % respectively of preterm infants <28 days of age, highlighting the need for early diagnosis and treatment.


Subject(s)
Bronchopulmonary Dysplasia , Hypertension, Pulmonary , Infant, Premature, Diseases , Bronchopulmonary Dysplasia/complications , Bronchopulmonary Dysplasia/diagnosis , Gestational Age , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Infant , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature
9.
Int J Biol Macromol ; 210: 403-414, 2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35526768

ABSTRACT

Curcumin, a principal component of Curcuma longa, has a long history of being used topically for wound healing. However, poor aqueous solubility of curcumin leads to poor topical absorption. Recently, gelatin based gel has been reported to overcome this issue. However, the release of curcumin from gelatin gel in the bioavailable or easily absorbable form is still a challenge. The present study reports the development of a composite gel prepared from gelatin, F127 and lecithin using temperature dependant gelation and loading of curcumin within it. Notably, the composite gel facilitated the release of curcumin entrapped within vesicles of ~400 nm size. Further, the composite gel exhibited increase in the storage modulus or gel strength, stability, pore size and hydrophobicity as compared to only gelatin gel. Finally, wound healing assay in murine model indicated that curcumin delivered through composite gel showed a significantly faster healing as compared to that delivered through organic solvent. This was also validated by histopathological and biochemical analysis showing better epithelization and collagen synthesis in the group dressed with curcumin containing composite gel. In conclusion, composite gel facilitated the release of bioavailable or easily absorbable curcumin which in turn enhanced the wound healing.


Subject(s)
Curcumin , Animals , Curcumin/pharmacology , Gelatin , Lecithins , Mice , Polyethylenes , Polypropylenes , Wound Healing
10.
J Biomed Mater Res A ; 110(2): 304-315, 2022 02.
Article in English | MEDLINE | ID: mdl-34355509

ABSTRACT

In this study, pluronic stabilized gelatin nanocomposite of varying hydrophilic-lipophilic balance (HLB) were synthesized to study the effect of surface hydrophobicity on their cellular uptake and in turn the delivery of a model hydrophobic bioactive compound, curcumin (CUR). Notably, the variation in HLB from 22 to 8 did not cause much change in morphology (~spherical) and surface charge (~ -6.5 mV) while marginally reducing the size of nanocomposite from 165 ± 097 nm to 134 ± 074 nm. On contrary, nanocomposites exhibited a very significant increase in their numbers, hydrophobicity as well as CUR loading with decreasing HLB values (22-8) of pluronic. Further, the cellular uptake of CUR through pluronic-gelatin nanocomposites was studied in human lung carcinoma (A549) cells. The results indicated that cellular uptake of CUR through nanocomposites followed the order HLB 22 > HLB 18 > HLB 15 > HLB 8. This was also reflected in terms of the decrease in cytotoxicity of CUR through nanocomposite of HLB 8 as compared to that of HLB 22. Interestingly, bare nanocomposite of HLB 8 showed significantly higher cytotoxicity as compared to that of HLB 22. Together these results suggested that although higher hydrophobicity of the gelatin-pluronic nanocomposite facilitated higher entrapment of CUR, the carrier per se became toxic due to its hydrophobic interaction with lipid bilayer of plasma membrane. Thus, HLB parameter is very important in designing hybrid nanocomposite systems involving protein and pluronic to ensure both bio-compatibility of the carrier and the optimum cellular delivery of the pay load.


Subject(s)
Curcumin , Nanocomposites , Nanoparticles , Curcumin/chemistry , Curcumin/pharmacology , Drug Carriers , Drug Delivery Systems , Gelatin , Humans , Hydrophobic and Hydrophilic Interactions , Nanocomposites/chemistry , Nanocomposites/toxicity , Nanoparticles/chemistry , Particle Size , Poloxamer/chemistry
11.
Pediatr Clin North Am ; 68(5): 1055-1070, 2021 10.
Article in English | MEDLINE | ID: mdl-34538298

ABSTRACT

COVID-19 has afflicted the health of children and women across all age groups. Since the outbreak of the pandemic in December 2019, various epidemiologic, immunologic, clinical, and pharmaceutical studies have been conducted to understand its infectious characteristics, pathogenesis, and clinical profile. COVID-19 affects pregnant women more seriously than nonpregnant women, endangering the health of the newborn. Changes have been implemented to guidelines for antenatal care of pregnant women, delivery, and newborn care. We highlight the current trends of clinical care in pregnant women and newborns during the COVID-19 pandemic.


Subject(s)
COVID-19/diagnosis , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/prevention & control , Pregnancy Outcome/epidemiology , Prenatal Care/methods , COVID-19/transmission , Delivery, Obstetric/statistics & numerical data , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy
13.
Pediatr Dev Pathol ; 24(5): 430-437, 2021.
Article in English | MEDLINE | ID: mdl-34048316

ABSTRACT

OBJECTIVE: Correlation of BPD with placental pathology is important for clarification of the multifactorial pathogenesis of BPD; however, previous reports have yielded varying results. We report placental findings in no/mild BPD compared to moderate/severe BPD, and with and without pulmonary hypertension (PH). METHODS: Eligible infants were 230/7-276/7 weeks gestational age. BPD was defined by the need for oxygen at ≥28 days with severity based on need for respiratory support at ≥36 weeks. Acute and chronic inflammatory placental lesions and lesions of maternal and fetal vascular malperfusion were examined. RESULTS: Of 246 eligible infants, 146 (59%) developed moderate/severe BPD. Thirty-four (23%) infants developed PH, all but 1 being in the moderate/severe BPD group. Chronic deciduitis (32% vs 16%, P = .003), chronic chorioamnionitis (23% vs 12%, P = .014), and ≥ 2 chronic inflammatory lesions (13% vs 3%, P = .007) were more frequent in the moderate/severe BPD group. Development of PH was associated with placental villous lesions of maternal vascular malperfusion (30% vs 15%, P = .047). CONCLUSIONS: The association of chronic inflammatory placental lesions with BPD severity has not been previously reported. This supports the injury responsible for BPD as beginning before birth in some neonates, possibly related to cytokines associated with these chronic inflammatory lesions.


Subject(s)
Bronchopulmonary Dysplasia/etiology , Infant, Extremely Premature , Placenta Diseases/physiopathology , Placenta/pathology , Adult , Case-Control Studies , Chronic Disease , Female , Humans , Hypertension, Pulmonary/etiology , Infant, Newborn , Logistic Models , Male , Patient Acuity , Placenta/blood supply , Placenta/physiopathology , Placenta Diseases/pathology , Pregnancy , Retrospective Studies
15.
Free Radic Res ; 55(6): 641-654, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33555213

ABSTRACT

Antioxidant activity of organoselenium compounds belonging to different classes i.e. functionalized aliphatic, aromatic and cyclic selenoethers, are compared on the basis of their ability to scavenge reactive oxygen species like hydroxyl and peroxyl radicals and to exhibit glutathione peroxidase (GPx) like catalytic activity. The comparative analysis has revealed that the antioxidant activity of the organoselenium compounds show direct correlation with the energy of the highest occupied molecular orbital (HOMO) and neighboring group participation that stabilizes the reaction intermediate. Finally, structural features responsible for improving the rate of reaction of organoselenium compounds with free radical/molecular oxidants have been discussed on the basis of the compounds screened at our institute.


Subject(s)
Antioxidants/chemistry , Free Radical Scavengers/chemistry , Organoselenium Compounds/chemistry , Oxidation-Reduction , Humans
16.
Pulm Pharmacol Ther ; 66: 101986, 2021 02.
Article in English | MEDLINE | ID: mdl-33338661

ABSTRACT

PURPOSE: There is increasing research into novel techniques of administering surfactant to preterm infants (PTIs) with respiratory distress syndrome (RDS) receiving non-invasive respiratory support (NIRS). Although aerosolized surfactant (AS) is promising in PTIs receiving NIRS, the optimal surfactant dose and formulation, drug-device combination and patient profile is not known. The objective of this randomized clinical trial was to investigate the feasibility, safety, efficacy and impact of four dosing schedules of AS using two nebulizers in PTIs with RDS stratified by gestational age (GA). METHODS: PTIs with RDS receiving pre-defined NIRS for ≤8 h were assigned to 4 A S dosing schedules and 2 nebulizers within three GA strata (I = 240/7-286/7, II = 290/7-326/7, III = 330/7-366/7 weeks). There was no contemporaneous control group; at the recommendation of the Data Monitoring Committee, data was collected retrospectively for control infants. RESULTS: Of 149 subjects that received AS, the median age at initiation of the 1st dose and duration was 5.5 and 2.4 h respectively. There were 29 infants in stratum I, and 60 each in strata II and III. Of infants <32 weeks GA, 94% received caffeine prior to AS. Fifteen infants (10%) required intubation within 72 h; the rates were not significantly different between GA strata, dosing schedules and nebulizers for infants who received aerosolized surfactant. Compared to retrospective controls, infants who received AS were less likely to need intubation within 72 h in both the intention-to-treat (32% vs. 11%) and the per-protocol (22% vs. 10%) analyses (p < 0.05) with GA stratum specific differences. AS was well tolerated by infants and clinical caregivers. Commonest adverse events included surfactant reflux from nose and mouth (18%), desaturations (11%), and increased secretions (7%). CONCLUSIONS: We have demonstrated the feasibility, absence of serious adverse events and short-term efficacy of four dosing schedules of AS in the largest Phase II clinical trial of PTIs 24-36 weeks' GA with RDS receiving NIRS (ClinicalTrials.gov NCT02294630). The commonest adverse events noted were surfactant reflux and desaturations; no serious adverse effects were observed. Infants who received AS were less likely to receive intubation within 72 h compared to historical controls. AS is a promising new therapy for PTIs with RDS.


Subject(s)
Biological Products , Respiratory Distress Syndrome, Newborn , Humans , Infant , Infant, Newborn , Infant, Premature , Respiratory Distress Syndrome, Newborn/drug therapy , Retrospective Studies
17.
Int J Pharm ; 586: 119522, 2020 Aug 30.
Article in English | MEDLINE | ID: mdl-32534159

ABSTRACT

Gelatin based nanocarriers have major limitation of shorter circulation half-life (t1/2). Present study addressed this issue by conjugating gelatin with folate followed by nanoprecipitation in presence of polysorbate 80 to form folate attached gelatin nanoparticles (GNP-F). The folic acid was conjugated with gelatin through the formation of amide linkage with a maximum conjugation yield of ~69%. Cryo-SEM analysis indicated that unconjugated gelatin nanoparticles (GNP) and GNP-F were spherical of nearly identical size of ~200 nm. The irinotecan (IRI)-loading efficiency estimated for IRI-GNP and IRI-GNP-F was 6.6 ± 0.42% and 11.2 ± 0.73% respectively and both formulations showed faster release of IRI at acidic pH (~5) than at physiological pH (~7). Further IRI-GNP-F demonstrated significantly higher cytotoxicity in folate receptor (FR)-positive HeLa cells than the unconjugated IRI-GNP nanoparticles confirming active targeting. Subsequently the antitumor activity of above formulations in FR-positive fibrosarcoma (syngeneic) tumor-bearing mice followed the order of IRI-GNP-F > IRI-GNP > free IRI. The pharmacokinetic evaluation of IRI-GNP and IRI-GNP-F revealed that encapsulation of IRI within GNP without folate improved its plasma maximum concentration (Cmax). However, folate conjugation of GNP remarkably improved the t1/2 of IRI. Taken together, folate as a targeting ligand modulates the pharmacokinetic property of IRI loaded GNP to favor active verses passive targeting.


Subject(s)
Folic Acid/chemistry , Irinotecan/administration & dosage , Nanoparticles , Topoisomerase I Inhibitors/administration & dosage , A549 Cells , Animals , Drug Carriers/chemistry , Female , Fibrosarcoma/drug therapy , Fibrosarcoma/pathology , Folate Receptors, GPI-Anchored/metabolism , Gelatin/chemistry , Half-Life , HeLa Cells , Humans , Hydrogen-Ion Concentration , Irinotecan/pharmacokinetics , Irinotecan/pharmacology , Mice , Particle Size , Polysorbates/chemistry , Topoisomerase I Inhibitors/pharmacokinetics , Topoisomerase I Inhibitors/pharmacology
18.
Pediatr Neonatol ; 61(3): 290-299, 2020 06.
Article in English | MEDLINE | ID: mdl-32217025

ABSTRACT

BACKGROUND: Bronchopulmonary Dysplasia (BPD) is the commonest morbidity in extremely preterm infants (PTIs). Risk factors for BPD have been described in the era before the widespread availability of non-invasive ventilation (NIV) in the delivery room (DR). The objective of this study is to identify risk factors for Moderate/Severe BPD in an era of widespread availability of NIV in the DR. METHODS: Detailed antenatal and postnatal data were abstracted for PTIs, 230/7-276/7 weeks GA. Multivariate logistic regression and classification and regression tree analyses (CART) identified predictors for the primary outcome of Moderate/Severe BPD. RESULTS: Of 263 eligible infants, 59% had Moderate/Severe BPD. Moderate/Severe BPD was significantly associated with birthweight, gender, DR intubation and surfactant compared to No/Mild BPD. Of infants not intubated in the DR, 40% with No/Mild BPD and 80% with Moderate/Severe BPD received intubation by 48 hours (p < 0.05). Infants with Moderate/Severe BPD received longer duration of oxygen and mechanical (MV). On logistic regression, birthweight, gender, oxygen concentration, cumulative duration of oxygen and MV, surfactant, and blood transfusions predicted Moderate/Severe BPD. Both CART analysis and logistic regression showed duration of oxygen and MV to be the most important predictors for Moderate/Severe BPD. CONCLUSIONS: In an era of increasing availability of NIV in the DR, lower birthweight, male gender, surfactant treatment, blood transfusions and respiratory support in the first 2-3 weeks after birth predict Moderate/Severe BPD with high sensitivity and specificity. The majority of these infants received intubation within 48 hours of birth (97%). These data suggest that early failures of NIV represent opportunities for improvement of NIV techniques and of non-invasive surfactant to avoid intubation in the first 48 hours. Furthermore, these risk factors may allow earlier identification of infants most likely to benefit from interventions to prevent or decrease severity of BPD.


Subject(s)
Bronchopulmonary Dysplasia/etiology , Adult , Birth Weight , Bronchopulmonary Dysplasia/prevention & control , Female , Humans , Infant, Extremely Premature , Infant, Newborn , Logistic Models , Male , Noninvasive Ventilation , Pregnancy , Pulmonary Surfactants/therapeutic use , Risk Factors
19.
J Phys Chem B ; 124(17): 3591-3601, 2020 04 30.
Article in English | MEDLINE | ID: mdl-32172568

ABSTRACT

The role of gold nanoparticles (AuNPs) in the degradation of tyrosine intermediates formed during the radiation-induced •OH reaction with tyrosine at pH 6.5 is investigated by measuring the radiolytic yields, G, of tyrosine (-Tyr), dityrosine (DT), and 3,4 dihydroxyphenylalanine (DOPA). The G(DT) is doubled, whereas G(-Tyr) calculated is halved in the presence of 6.0 × 10-10 mol dm-3 AuNPs. Pulse radiolysis studies are carried out to elucidate the mechanism and nature of the transient formed in the reaction of •OH and •N3 with tyrosine. The formation of tyrosyl radical in the presence of AuNPs is found to be a major pathway through the decay of tyrosine-•OH adducts via the water elimination reaction, which is found to be 3× faster in the presence of AuNPs. Quantum chemical calculations on the system showed favorable formation of the tyrosine-AuNP complex. A new plausible mechanism of tyrosine-AuNP complex acting as a Lewis type catalyst in the decay of tyrosine-•OH adducts leading to reduced DOPA formation is proposed. The proposed mechanism is also complemented by the electronic spectra and energetics of the reaction of •OH with tyrosine using density functional theory calculations. Significantly, the H-shift reaction of ortho-tyrosine-•OH adducts is also found to be energetically viable. The investigation provides a new physical insight into the effect of AuNPs on the decay of free-radical transient species and demonstrates the potential of radiation chemical techniques and quantum chemical calculations as a tool for understanding the impact of metal nanoparticles in free-radical oxidation of amino acids, which is important in the use of metal nanoparticles for biomedical applications.

20.
Nanoscale Adv ; 2(3): 1214-1227, 2020 Mar 17.
Article in English | MEDLINE | ID: mdl-36133061

ABSTRACT

We report, for the first time, the development of gamma radiation resistant polysulfone (Psf)-nanodiamond (ND) composite membranes with varying concentrations of NDs, ranging up to 2 wt% of Psf. Radiation stability of the synthesized membranes was tested up to a dose of 1000 kGy. To understand the structure-property correlationship of these membranes, multiple characterization techniques were used, including field-emission scanning electron microscopy, atomic force microscopy, drop shape analysis, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, gel permeation chromatography, positron annihilation spectroscopy, and small angle X-ray scattering. All the composite membranes exhibited enhanced radiation resistance properties, with 0.5% loading of NDs as the optimum. Compared to the radiation stability of Psf membranes up to a dose of 100 kGy, the optimum composite membranes are found to be stable up to a radiation dose of 500 kGy, owing to the unique surface chemistry of NDs and interfacial chemistry of Psf-ND composites. Experimental findings along with the Monte Carlo simulation studies confirmed a five times enhanced life-span of the composite membranes in an environment of the intermediate level radioactive waste, compared to the control Psf membrane.

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