Biomimicking dual drug eluting twisted electrospun nanofiber yarns for post-operative wound healing.

The morbidity rate following a surgical procedure increasing rapidly in the cases associated with surgical site infections. Traditional sutures lack the ability to deliver drugs as the incorporation of the drug in their structure would hamper their mechanical properties. To prevent such infections, we developed an extracellular matrix mimicking electrospun nanofibrous yarns of poly-(D,L)-lactic acid and polyvinyl alcohol loaded with vancomycin and ferulic acid, prepared by uniaxial electrospinning technique.In-vitrocharacterization such as scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, tensile strength testing, degradation studies, and antimicrobial studies along within-vivoevaluation done with help of incision wound healing rat model and simultaneous testing of microbial load in the incised tissue. Thein-vitrostudies indicated the nanofiber yarns have size range 200-300 nm with a tensile strength of 7.54 ± 0.58 MPa. The dual drug-loaded yarn showed sustained drug release over a period of 48 h.In-vitrowater uptake and biodegradation data indicated optimum results suitable for suturing applications. Antimicrobial study showed excellent antimicrobial activity against bothS. aureus and E. coli.Results obtained fromin-vivostudy suggested excellent wound healing potential of nanofiber yarns as compared with commercial silk sutures. The histopathological studies confirmed restoring ability of nanofiber yarn to the normal skin structure. Enzyme-linked immunosorbent assay (ELISA) study revealed the downregulation of inflammatory markers i.e. TNF-alpha and IL-6, making nanofibers sutures suitable for surgical wound healing applications. Overall, the present study may conclude that the developed dual drug-loaded nanofiber yarns have excellent potential in surgical wound healing applications.

Lipid Based Aqueous Core Nanocapsules (ACNs) for Encapsulating Hydrophillic Vinorelbine Bitartrate: Preparation, Optimization, Characterization and In vitro Safety Assessment for Intravenous Administration.

BACKGROUND: Vinorelbine bitartrate (VRL) is an antimitotic agent approved by FDA for breast cancer and non-small cell lung cancer (NSCLC) in many countries. However, high aqueous solubility and thermo degradable nature of VRL limited the availability of marketed dosage forms. OBJECTIVES: The current work is focused on the development of lipid based aqueous core nanocapsules which can encapsulate the hydrophilic VRL in the aqueous core of nanocapsules protected with a lipidic shell which will further provide a sustained release. METHODS: The ACNs were prepared by double emulsification technique followed by solvent evaporation. Box Behnken Design was utilized to optimize the formulation and process variables. Thirteen batches were generated utilizing lipid concentration, surfactant concentration and homogenizer speed as dependent variables (at three levels) and particle size and encapsulation efficiency as critical quality attributes. The ACNs were characterized for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, morphology by Transmission Electron Microscopy (TEM) and in vitro release. The ACNs were further evaluated for safety against intravenous administration by haemocompatibility studies. RESULTS: Results demonstrated that lipidic nanocapsules enhanced the entrapment efficiency of VRL up to 78%. Transmission Electron Microscopy revealed spherical shape of ACNs with core-shell structure. The GMS-VRL-ACNs showed that release followed Korsemeyer peppas kinetics suggesting Fickian diffusion. Moreover, the compliance towards haemocompatibility studies depicted the safety of prepared nanocapsules against intravenous administration. CONCLUSION: ACNs were found to be promising in encapsulating high aqueous soluble anticancer drugs with enhanced entrapment and safety towards intravenous administration.

Cell proliferation influenced by matrix compliance of gelatin grafted poly(d,l-Lactide) three dimensional scaffolds.

Surface and mechanical properties of the biomaterials are determinants of cellular responses. In our previous study, star-shaped poly(d,l-Lactide)-b-gelatin (ss-pLG) was reported for possessing improved cellular adhesion and proliferation. Here, we extended our investigation to establish the cellular compatibility of gelatin-grafted PDLLA with respect to mechanical properties of biological tissues. In this view, linear PDLLA-b-gelatin (l-pLG) was synthesized and tissue-level compatibility of 1-pLG and ss-pLG against fibroblasts (L929), myoblasts (C2C12) and preosteoblasts (MG-63) was examined. The cell proliferation of C2C12 was significantly higher within l-pLG scaffolds, whereas L929 showed intensified growth within ss-pLG scaffolds. The difference in cell proliferation may be attributed to the varying mechanical properties of scaffolds; where the stiffness of l-pLG scaffolds was notably higher than ss-pLG scaffolds, most likely due to the variable levels of gelatin grafting on the backbone of PDLLA. Therefore, gelatin grafting can be used to modulate mechanical property of the scaffolds and this study reveals the significance of the matrix stiffness to produce the successful 3D scaffolds for tissue engineering applications.

Catechin-loaded Eudragit microparticles for the management of diabetes: formulation, characterization and in vivo evaluation of antidiabetic efficacy.

Catechin (CT) is natural molecule proved for antidiabetic activity. Clinical application of CT is highly restricted because of its low bioavailability and ineffectiveness in in vivo conditions. Therefore, the main objective of the present investigation was to formulate CT-loaded Eudragit RS 100 microparticles and evaluated for its potential against diabetes. CT microparticles showing highest entrapment efficiency of 92.3 ± 6.5% and higher percentage yield of 63.46 ± 4.3% was selected as optimised formulation. CT microparticles treated rats showed significantly lower blood glucose, cholesterol, LDL, free fatty acid and triglyceride concentrations in comparison to pristine CT-treated rats. The glucose and lipid profiles of microparticle formulation were akin to normal rats. Moreover, CT microparticles did not produce obesity even after 60 days which is a comment side effect of antidiabetic drugs. These results indicate that the CT microparticles can be applied as potential and safe carrier for the treatment of diabetes.

Pharmacokinetics, biodistribution, in vitro cytotoxicity and biocompatibility of Vitamin E TPGS coated trans resveratrol liposomes.

The clinical application of trans resveratrol (RSV) in glioma treatment is largely limited because of its rapid metabolism, fast elimination from systemic circulation and low biological half life. Therefore, the objectives of this study were to enhance the circulation time, biological half life and passive brain targeting of RSV using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) coated liposomes (RSV-TPGS-Lipo). In addition to basic liposomal characterizations, in vitro anticancer potential against C6 glioma cell lines and cellular internalization of liposomes were carried out by MTT assay and confocal laser scanning microscopy (CLSM), respectively. Pharmacokinetics and tissue distribution studies were also carried out after intravenous administration in Charles Foster rats. RSV-TPGS-Lipo 2 showed significantly higher cytotoxicity than RSV-Lipo (uncoated liposomes) and RSV. Both uncoated and TPGS coated liposomes showed excellent cellular uptake. RSV, RSV-Lipo and RSV-TPGS-Lipo 2 were found to be haemocompatible and safe after i.v. administration. Area under the curve (AUC) and plasma half life (t1/2) after i.v. administration of RSV-TPGS-Lipo 2 was found to be approximately 5.73 and 6.72 times higher than that of RSV-Lipo as well as 29.94 and 29.66 times higher than that of RSV, respectively. Thus, the outcome indicates that RSV-TPGS-Lipo 2 is a promising carrier for glioma treatment with improved pharmacokinetic parameters. Moreover, brain accumulation of RSV-Lipo and RSV-TPGS-Lipo 2 was found to be significantly higher than that of RSV (P<0.05). Results are suggesting that both RSV-Lipo and RSV-TPGS-Lipo 2 are the promising tools of RSV for the treatment of brain cancer.

Transferrin liposomes of docetaxel for brain-targeted cancer applications: formulation and brain theranostics.

Diagnosis and therapy of brain cancer was often limited due to low permeability of delivery materials across the blood-brain barrier (BBB) and their poor penetration into the brain tissue. This study explored the possibility of utilizing theranostic d-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) liposomes as nanocarriers for minimally invasive brain-targeted imaging and therapy (brain theranostics). The aim of this work was to formulate transferrin conjugated TPGS coated theranostic liposomes, which contain both docetaxel and quantum dots (QDs) for imaging and therapy of brain cancer. The theranostic liposomes with and without transferrin decoration were prepared and characterized for their particle size, polydispersity, morphology, drug encapsulation efficiency, in-vitro release study and brain theranostics. The particle sizes of the non-targeted and targeted theranostic liposomes were found below 200 nm. Nearly, 71% of drug encapsulation efficiency was achieved with liposomes. The drug release from transferrin conjugated theranostic liposomes was sustained for more than 72 h with 70% of drug release. The in-vivo results indicated that transferrin receptor-targeted theranostic liposomes could be a promising carrier for brain theranostics due to nano-sized delivery and its permeability which provided an improved and prolonged brain targeting of docetaxel and QDs in comparison to the non-targeted preparations.

Transferrin receptor-targeted vitamin E TPGS micelles for brain cancer therapy: preparation, characterization and brain distribution in rats.

The effective treatment of brain cancer is hindered by the poor transport across the blood-brain barrier (BBB) and the low penetration across the blood-tumor barrier (BTB). The objective of this work was to formulate transferrin-conjugated docetaxel (DTX)-loaded d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for targeted brain cancer therapy. The micelles with and without transferrin conjugation were prepared by the solvent casting method and characterized for their particle size, polydispersity, drug encapsulation efficiency, drug loading, in vitro release study and brain distribution study. Particle sizes of prepared micelles were determined at 25 °C by dynamic light scattering technique. The external surface morphology was determined by transmission electron microscopy analysis and atomic force microscopy. The encapsulation efficiency was determined by spectrophotometery. In vitro release studies of micelles and control formulations were carried out by dialysis bag diffusion method. The particle sizes of the non-targeted and targeted micelles were <20 nm. About 85% of drug encapsulation efficiency was achieved with micelles. The drug release from transferrin-conjugated micelles was sustained for >24 h with 50% of drug release. The in vivo results indicated that transferrin-targeted TPGS micelles could be a promising carrier for brain targeting due to nano-sized drug delivery, solubility enhancement and permeability which provided an improved and prolonged brain targeting of DTX in comparison to the non-targeted micelles and marketed formulation.

Investigations on agglomeration and haemocompatibility of vitamin E TPGS surface modified berberine chloride nanoparticles.

The objective of the present study is to investigate the influence of surface modification on systemic stability of NPs. Vitamin E TPGS (1% w/v) was used for surface modification of berberine chloride nanoparticles. Naked and surface modified NPs were incubated in different SBFs (pH 6.8 and 7.4) with or without bile salts and human plasma. NPs were observed for particle agglomeration and morphology by particle size analyzer and TEM, respectively. The haemocompatibility studies were conducted on developed NPs to evaluate their safety profile. The surface modified NPs were stable compared to naked NPs in different SBFs due to the steric stabilization property of vitamin E TPGS. Particle agglomeration was not seen when NPs were incubated in SBF (pH 6.8) with bile salts. No agglomeration was observed in NPs after their incubation in plasma but particle size of the naked NPs increased due to adhesion of plasma proteins. The TEM images confirmed the particle size results. DSC and FT-IR studies confirmed the coexistence of TPGS in surface modified NPs. The permissible haemolysis, LDH release, and platelet aggregation revealed that NPs were compatible for systemic administration. Thus, the study illustrated that the surface modification is helpful in the maintenance of stability of NPs in systemic conditions.

Multicystic dysplastic kidney: a retrospective study.

OBJECTIVE: To report the renal structural and functional anomalies in children with multicystic dysplastic kidneys. METHODS: Retrospective descriptive analysis of 47 children with multicystic dysplastic kidney seen in a pediatric nephrology unit over a period of 6 years. RESULTS: Antenatal diagnosis of multicystic dysplastic kidney was made in 34 (72.3%) patients. On follow up of 31 children for more than 12 months, 21 (68%) had involution, 4 [13%] had non-regression, and 4 (13%) were nephrectomized. Vesico-ureteric reflux (n=13; 28%) was the commonest renal abnormality. The serum creatinine values were higher (P=0.006) in children with contralateral reflux. Sub-nephrotic proteinuria was noted in 9 (29%) and was significantly associated with complete involution (P=<0.023). None of the patients developed hypertension and 2 (6.4%) had renal failure. CONCLUSIONS: Close nephrological follow-up is needed in children with multicystic dysplasia of kidneys.

Descriptive study of clinical profile and benefit of therapy in childhood hypercalciuria.

Clinical, biochemical, and ultrasonographic findings in 91 consecutive children presenting with hypercalciuria were analyzed along with the results of treatment to determine the clinical profile of hypercalciuria and its outcome. Hypercalciuria was common in children aged 1-5 years (39.6%), and hematuria was the most frequent symptom. There was no significant difference between 24-hour urinary calcium and random urinary calcium/creatinine ratio values between males and females. The random urinary calcium/creatinine ratio was found to be useful for screening and also for documenting the benefit of therapy. The children were essentially treated with thiazides, and the majority showed a good response, with a good overall outcome on follow-up.

Copolymers of poly(lactic acid) and D-α-tocopheryl polyethylene glycol 1000 succinate-based nanomedicines: versatile multifunctional platforms for cancer diagnosis and therapy.

INTRODUCTION: The major drawbacks associated with most of the anti-cancer drugs are their potential adverse effects. Distribution of these drugs throughout the body causes untoward adverse effects and less accumulation of drug at the site of tumors also causes decrease in therapeutic efficacy. Targeted nanomedicines are the emerging systems to improve the targetability of drug to the tumor site and to reduce the toxicity with maximum efficacy. Copolymers of poly-lactic acid (PLA) and D-α-tocopheryl polyethylene glycol 1000 succinate (Vitamin-E TPGS or TPGS) are innovative materials being actively investigated for the fabrication of non-targeted and targeted nanomedicines for diagnosis and therapy of cancer. AREAS COVERED: In this review, different nanomedicines of copolymers such as poly-lactic acid - polyoxyethylene sorbitan monooleate (PLA - Tween® 80), poly-lactic acid - poly-ethyleneglycol (PLA-PEG), poly-lactic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) and TPGS-based nanomedicines (i.e., TPGS emulsified polymeric nanoparticles, TPGS prodrugs, TPGS liposomes, and TPGS micelles) for the diagnosis and therapy of cancer have been discussed. EXPERT OPINION: PLA, PLA-Tween® 80, PLA-PEG, PLA-TPGS, and TPGS are the promising polymeric biomaterials well studied as cancer nanomedicines. These biomaterials have proved that they could be applied in the fabrication of multifunctional nanomedicines for the future needs in simultaneous diagnosis of cancer as well as targeted chemotherapy.

Chronic myeloid leukemia in a child with IgA nephropathy.

We report an 11 year old boy with IgA nephropathy developing chronic myeloid leukemia on follow-up. This association suggests that a B cell defect might be involved in the pathogenesis of these two conditions.

Experience of renal biopsy in children with nephrotic syndrome.

Percutaneous renal biopsy (PRB) is useful in childhood renal diseases. This study was done to determine the indications for renal biopsy in nephrotic children, to correlate the indications with histology and to document the complications of PRB. This study included 250 nephrotic children younger than 18 years old who had renal biopsy from January 1988 to December 2002. Ultrasonographic guidance was used in the latter part of the study. Coagulation profile and renal function assessment and blood group testing were done prior to biopsy. Children were monitored clinically during and after the procedure. All children had local anesthesia and 202 children also had short-acting general anesthesia. All biopsies were done on the left kidneys. The specimens were studied under light and immunofluorescent microscopy. All had a post-biopsy ultrasonography at 24 h. Biopsy was diagnostic in 95.2% of children, with a failure rate of 4.8%. The most common indication for biopsy was steroid-resistant nephrotic syndrome (65.2%), and minimal change disease (52.1%) was the most common histology, irrespective of the indications for renal biopsy. Mild (16.0%) and gross (16.8%) hematuria and subcapsular hematoma (6.0%) were the common complications. Fifty-five percent of the children had no complications. Only two children (0.8%) had biopsy site infection.