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At least 253 records · Page 14Linked to original sources
PubMed1982

Cesarean delivery in nulliparous women for failed oxytocin-augmented labor: route of delivery in subsequent pregnancy.

Fifty-eight patients experienced cesarean section for termination of their first term pregnancy subsequent to a failed trial of oxytocin therapy. Cephalopelvic disproportion and "failure to progress" were the sole indications for the initial cesarean section. All 58 women returned to our hospital for a subsequent trial of labor during the years 1977-1979 inclusive, and 40 of the 58 were able to have a vaginal delivery. Parameters investigated included first and subsequent pregnancy birth weights; birth weight difference; duration and maximal dose of oxytocin; status of the cervix at admission, prior to oxytocin, and before cesarean section; and the clinical and/or radiologic estimation of pelvic dimensions. Subsequent birth weight less than 3,500 gm was the only statistically significant factor associated with a high rate of vaginal delivery.

Birth Weight↗
PubMed1984

Abdominovaginal delivery: modification of the cesarean section operation to facilitate delivery of the impacted head.

The abdominovaginal delivery is a modification of the cesarean section operation in the presence of an impacted fetal head, usually after a prolonged second stage of labor with ruptured membranes. With the legs abducted in either the "Whitmore" or the "frog" position, the wedged vertex is gently lifted with the cupped hand into the open transverse uterine incision, thereby reducing injury to the fetal head and the uterus. With the greater use of cesarean section operation and the sharp reduction in rotational and midforceps deliveries, the abdominovaginal procedure has an increasingly important place in our obstetric armamentarium.

Cesarean Section↗
PubMed1995

Development and in vitro evaluation of chitosan-based transdermal drug delivery systems for the controlled delivery of propranolol hydrochloride.

Membrane permeation-controlled transdermal drug delivery systems were prepared using the natural polymer, chitosan. An adhesive sealing technique was used to construct the devices. Propranolol hydrochloride was selected as the model drug for the present study. Chitosan membranes with different permeability to propranolol hydrochloride obtained by controlled cross-linking with glutaraldehyde were used to regulate the drug release in the devices. Chitosan gel was used as the drug reservoir. The ability of these devices to deliver the drug while supported on rabbit pinna skin was tested by conducting in vitro studies in modified Franz diffusion cells. The drug release profiles showed that the drug delivery is completely controlled by the devices. The rate of drug release was found to be dependent on the type of membrane used.

Administration, Cutaneous↗
PubMed2005

Neonatal impact of elective repeat cesarean delivery at term: a comment on patient choice cesarean delivery.

OBJECTIVE: The object of this study was to compare neonatal outcomes of term uncomplicated pregnancies delivered by scheduled repeat cesarean with outcomes of babies born to mothers intending to deliver vaginally. STUDY DESIGN: This retrospective cohort study describes neonatal outcomes of term uncomplicated pregnancies. Neonates of mothers intending to deliver vaginally (n = 3134) are compared with neonates born by elective repeat cesarean delivery prior to labor (n = 117). RESULTS: Neonates born by elective repeat cesarean are more frequently admitted to advanced care nurseries than infants born to mothers intending to deliver vaginally (risk ratio 3.58, 95% confidence interval 3.35-3.58). CONCLUSION: The decision to undergo scheduled cesarean delivery appears to negatively impact immediate neonatal outcomes.

Apgar Score↗
PubMed2004

Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs.

The oral delivery of hydrophobic drugs presents a major challenge because of the low aqueous solubility of such compounds. Self-emulsifying drug delivery systems (SEDDS), which are isotropic mixtures of oils, surfactants, solvents and co-solvents/surfactants, can be used for the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds. SEDDS can be orally administered in soft or hard gelatin capsules and form fine relatively stable oil-in-water (o/w) emulsions upon aqueous dilution owing to the gentle agitation of the gastrointestinal fluids. The efficiency of oral absorption of the drug compound from the SEDDS depends on many formulation-related parameters, such as surfactant concentration, oil/surfactant ratio, polarity of the emulsion, droplet size and charge, all of which in essence determine the self-emulsification ability. Thus, only very specific pharmaceutical excipient combinations will lead to efficient self-emulsifying systems. Although many studies have been carried out, there are few drug products on the pharmaceutical market formulated as SEDDS confirming the difficulty of formulating hydrophobic drug compounds into such formulations. At present, there are four drug products, Sandimmune and Sandimmun Neoral (cyclosporin A), Norvir (ritonavir), and Fortovase (saquinavir) on the pharmaceutical market, the active compounds of which have been formulated into specific SEDDS. Significant improvement in the oral bioavailability of these drug compounds has been demonstrated for each case. The fact that almost 40% of the new drug compounds are hydrophobic in nature implies that studies with SEDDS will continue, and more drug compounds formulated as SEDDS will reach the pharmaceutical market in the future.

Administration, Oral↗
PubMed2004

Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a thiomer/glutathione microparticulate delivery system.

It was the aim of this study to develop and evaluate a nasal microparticulate delivery system for human growth hormone (hGH) based on the thiomer polycarbophil-cysteine (PCP-Cys) in combination with the permeation mediator glutathione (GSH). Microparticles were prepared by dissolving PCP-Cys/GSH/hGH (7.5:1:1.5), PCP/hGH (8.5:1.5), and mannitol/hGH (8.5:1.5) in demineralized water, followed by lyophilization and micronization. Particles were evaluated with regard to size distribution and swelling behavior using a laser diffraction particle size analyzer. The release of fluorescence-labelled hGH from microparticles was determined in Franz diffusion chambers. In vivo studies in rats were performed comparing the nasal bioavailability achieved by PCP-Cys/GSH/hGH microparticles with that of unmodified PCP/hGH microparticles and mannitol/hGH powder. PCP-Cys/GSH/hGH and PCP/hGH microparticles showed a comparable size distribution (80% in the range of 4.8-23 microm) and swelled to almost fourfold size in phosphate-buffered saline (PBS). Both formulations exhibited almost identical sustained drug release profiles. The intranasal administration of the PCP-Cys/GSH/hGH microparticulate formulation resulted in a relative bioavailability of 8.11+/-2.15%, which represents a 3-fold and 3.3-fold improvement compared to that of PCP/hGH microparticles and mannitol/hGH powder, respectively. The study suggests that the PCP-Cys/GSH/hGH nasal microparticulate formulation might represent a promising novel tool for the systemic delivery of hGH.

Acrylic Resins↗
PubMed2004

Local drug delivery in restenosis injury: thermoresponsive co-polymers as potential drug delivery systems.

The success of percutaneous transluminal coronary angioplasty in treatment of acute coronary syndromes has been compromised by the incidence of restenosis. The physical insult of balloon insertion can damage or remove the endothelial monolayer, thereby generating a prothrombotic surface. The resulting inappropriate response to injury can also lead to penetration of inflammatory cells, conversion of the underlying media to a synthetic phenotype, deposition of extracellular matrix, constrictive remodeling, and neointimal hyperplasia. While stent implantation at the time of balloon insertion has offset some of these events, inflammatory responses to the implanted biomaterial (stent) and intimal hyperplasia are still prominent features of the procedure, leading in 20-30% of cases to in-stent restenosis within a year. Systemic delivery of drugs designed to offset in-stent restenosis injury has been largely unsuccessful, which has led to the development of strategies for coating stents with drugs for local delivery. Drug-eluting stents constitute an innovative means of further reducing the incidence of restenosis injury and clinical trials have shown encouraging results. This review focuses on properties of a class of environment-sensitive hydrogels, the N-isopropylacrylamide-based thermoresponsive co-polymers, on their potential roles as stent coatings, on their demonstrated ability to incorporate and release drugs that modify vascular endothelial and smooth muscle cell functions, and on issues that still await clarification, prior to their adoption in a clinical setting.

Acrylamides↗
PubMed2001

Homing markers for atherosclerosis: applications for drug delivery, gene delivery and vascular imaging.

Endothelial dysfunction plays a major role in the pathogenesis of atherosclerosis. Pro-inflammatory cytokines such as interleukin-1 beta and tumour necrosis factor alpha activate endothelial cells changing their resting phenotype to become pro-adhesive, pro-thrombotic and pro-atherogenic. Phage display in vivo biopanning has been used to identify peptide sequences that home to diseased regions of the vessel wall in low density lipoprotein receptor (LDLr) knockout mice. In LDLr knockout mice, peptide sequence determinants exhibiting organ specificity have been isolated. These sequences have applications for gene delivery, drug delivery and for improving contrast agents for vascular imaging.

Animals↗
PubMed2003

Chitin/PLGA blend microspheres as a biodegradable drug delivery system: a new delivery system for protein.

Novel chitin/PLGAs and chitin/PLA based microspheres were developed for the delivery of protein. These biodegradable microspheres were prepared by polymers blending and wet phase-inversion methods. The parameters such as selected non-solvents, temperature of water and ratio of polylactide to polyglycolide were adjusted to improve thermodynamic compatibility of individual polymer (chitin and PLGAs or chitin/PLA), which affects the hydration and degradation properties of the blend microspheres. Triphasic pattern of drug release model is observed from the release of protein from the chitin/PLGAs and chitin/PLA microspheres: the initially fast release (the first phase), the following slow release (the second phase) and the second burst release (the third phase). Formulations of the blends, which are based on the balance among the hydration rate of the chitin phase and degradation of chitin/PLA and PLGA phase, can lead to a controllable release of bovine serum albumin (BSA). In conclusion, such a chitin/PLGA 50/50 microsphere is novel and interesting, and may be used as a protein delivery system.

Absorbable Implants↗
PubMed2001

Bone-specific delivery and sustained release of diclofenac, a non-steroidal anti-inflammatory drug, via bisphosphonic prodrug based on the Osteotropic Drug Delivery System (ODDS).

We have newly synthesized osteotropic diclofenac with bisphosphonic moiety (DIC-BP) based on the concept of Osteotropic Drug Delivery System (ODDS) and investigated its potency of site-specific and controlled delivery of diclofenac to the bone in rats. After intravenous injection into rats, DIC-BP was predominantly distributed in the skeleton. DIC-BP once incorporated in the bone was gradually eliminated (t(1/2)=9.7 days), releasing diclofenac into the bone compartment. As a result, the bone concentration of regenerated diclofenac was apparently constant over 28 days. Furthermore, we evaluated the anti-inflammatory effects of DIC-BP compared with diclofenac (sodium salt) in adjuvant-induced arthritic rats. The mean effective doses (ED(50)) were 0.55 mg/kg and 1.3 mg/kg for daily oral administration of diclofenac and weekly intravenous injection of DIC-BP, respectively. Considering the frequency of medication of 17 times for diclofenac and 4 times for DIC-BP in the experimental period, ED(50) was corrected to 9.4 and 5.2 mg/kg (per experimental period) for diclofenac and DIC-BP, respectively. Moreover, DIC-BP exhibited no side effects of gastrointestinal damage, typical of non-steroidal anti-inflammatory drugs. Thus, ODDS of diclofenac shows promise as an approach for highly potent and non-toxic therapy of diclofenac, with less frequent medication.

Animals↗
PubMed2002

Immersion delivery of plasmid DNA. I. A study of the potentials of a liposomal delivery system in rainbow trout (Oncorhynchus mykiss) fry.

A successful regime for intramuscular injection of naked DNA is developed in fish, but the exploration of other ways of administration has not yet been studied in any detail. Immersion is a delivery route offering many advantages compared to conventional ways of administration. Applying cationic liposomes as a delivery system for DNA by this route, however, is met with severe toxicity problems. In this report, the underlying mechanisms of the acute toxicity were investigated in vivo and in vitro. The most critical factor was found to be the charge of the liposomes. Cationic liposomes above a certain threshold concentration had a lethal effect in rainbow trout fry. In contrast, similar concentrations of neutral or anionic liposomes were not toxic. Furthermore, large liposome-mucin complexes were formed upon addition of mucin to cationic liposomes. This was not observed with neutral or anionic liposomes. Lipoplexes were less toxic and interacted less with mucin compared to cationic liposomes. Hence, the mechanism of the acute toxicity in rainbow trout fry is suggested to be an interaction between the cationic liposomes and anionic components of gill mucin. The consequence is hypoxia and this is most likely the cause of acute toxicity observed in rainbow trout fry.

Animals↗
PubMed2003

Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors.

Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar in a mouse xenograft tumor model.

Animals↗
PubMed2003

Pharmacokinetics and delivery of the anti-influenza prodrug oseltamivir to the small intestine and colon using site-specific delivery capsules.

This study investigated the site-specific absorption of oseltamivir using targeted delivery and gamma scintigraphy. On four separate occasions, nine healthy male subjects each received a single 150 mg of oseltamivir administered via the Enterion capsule to the stomach, proximal small bowel, distal small bowel and the ascending colon. Pharmacokinetic parameters of oseltamivir and its carboxylate metabolite show that absorption was similar in the proximal and distal small bowel compared to stomach delivery, but reduced from the ascending colon, demonstrating that absorption-rate limited disposition occurred only for the ascending colon. The metabolite-to-parent ratios were minimally reduced. The results support the feasibility of modified-release formulation development whilst confirming the high and consistent oral bioavailability of oseltamivir.

Acetamides↗
PubMed1993

Liposome-mediated delivery of gallium to macrophage-like cells in vitro: demonstration of a transferrin-independent route for intracellular delivery of metal ions.

Gallium (Ga) prevents the activation of macrophages and might be useful as an immunosuppressive agent. It is taken up by the malignant cells through the transferrin (Tf) receptor pathway, but this pathway may be insufficient in the case of non-malignant cells. We studied the Tf-independent, liposome-mediated delivery of Ga to macrophage-like cells in vitro by a growth inhibition assay. The growth inhibitory properties of Ga for other types of cells was also evaluated. Ga complexed with nitrilotriacetate (GaNTA) and encapsulated in DSPG-liposomes was 16 and 48 times more potent for RAW 264 cells than free GaNTA and Ga-nitrate, respectively. CV1-P cells were also somewhat sensitive to liposomal Ga, but other cell lines with lower endocytotic capacity were insensitive. The inhibition of RAW 264 cell growth induced by liposomal or free GaNTA was partially reversed with iron-loading of the cells, indicating that this form of Ga causes an intracellular iron deficiency similar to that produced by Tf-bound Ga. Our results indicate that encapsulation of Ga in negatively charged liposomes provides a transferrin independent route for intracellular delivery of the compound to macrophages, which is of special interest in the treatment of autoimmune diseases, such as rheumatoid arthritis.

Ammonium Chloride↗
PubMed2002

Systemic delivery of human growth hormone using genetically modified tissue-engineered microvascular networks: prolonged delivery and endothelial survival with inclusion of nonendothelial cells.

Endothelial cells have the potential to provide efficient long-term delivery of therapeutic proteins to the circulation if a sufficient number of genetically modified endothelial cells can be incorporated into the host vasculature and if these cells persist for an adequate period of time. Here we describe the ability of nonendothelial cells to modulate the survival of implanted endothelial cells and their incorporation into host vasculature. Bovine aortic endothelial cells (BAECs) suspended in Matrigel and cultured in vitro remained spherical and decreased in number over time. Subcutaneous implantation of gels containing BAECs secreting human growth hormone (hGH) in mice initially resulted in detectable plasma hGH levels, which were undetectable after 2 weeks. When mixed with fibroblasts and suspended in Matrigel, hGH-secreting BAECs formed microvascular networks in vitro. Implantation of these gels resulted in plasma hGH levels that decreased slightly over 2 weeks and then remained stable for at least 6 weeks. BAECs incorporated into blood vessels within both the implant and fibrous capsule that surrounded and invaded implants. Within implants containing BAECs and fibroblasts, viable BAECs were present for at least 6 weeks at a higher density than in implants containing BAECs alone at 3 weeks. These results indicate that implanted BAECs can incorporate into host blood vessels and that inclusion of fibroblasts in this system prolongs BAEC survival and hGH delivery.

Animals↗
PubMed2005

Gamma scintigraphic evaluation of a miniaturized AERx pulmonary delivery system for aerosol delivery to anesthetized animals using a positive pressure ventilation system.

The purpose of this study was to characterize performance of a miniaturized AERx((R)) Pulmonary Delivery System designed for aerosol administration to large animal models. The miniaturized AERx System was developed through a systematic scaling down of the AERx System used for humans to allow for operation in certain animal models with lower inspiratory flow rates and inhaled volumes than those used for humans. We used gamma scintigraphy to characterize the in vivo particle deposition achieved with the miniaturized AERx System in two dogs. The dogs were 3-4 years old, and weighed 10.4 kg and 13.6 kg. Acepromazine was used as pre-anesthetic medication. Anesthesia was induced with 5% isoflurane. The trachea was intubated using an endotracheal tube (internal diameter 8.5 mm), and the dogs were ventilated using positive pressure during the exposure using the LRRI puff generator. An inhalation of aerosol was initiated by activation of the puff generator though the computer-controlled interface. Each dog inhaled approximately 0.8 L per puff, of which the aerosol volume comprised approximately 0.25 L, at a target flow rate of 15 L/min. The dogs were exposed to 10 AERx Strips in 10 puffs. The mass median aerodynamic diameter of the aerosolized formulation was approximately 1.25 microm with a fine particle fraction <3.5 microm of 0.976. The scintigraphic images showed uniform bilateral lung deposition following aerosol delivery with the AERx System. Total lung deposition for the two dogs was 10.7% and 18% of the loaded dose from the AERx Strip. The corresponding peripheral lung: inner lung (P/I) ratios were 0.83 and 0.75, suggestive of deposition in the deep lung. Only 0.1% to 0.2% of the loaded dose was exhaled. These results show the miniature AERx System can efficiently deliver aerosols to the deep lung of dogs. The miniaturized AERx System would be a valuable tool for conducting proof-of-concept studies as well as safety and tolerability analysis of inhaled drug candidates in large animal models.

Administration, Inhalation↗
PubMed1998

Cisplatin delivery by biodegradable polymer implant is superior to systemic delivery by osmotic pump or i.p. injection in tumor-bearing mice.

The use of biodegradable polymer implants to deliver cisplatin was compared with delivery by systemic injection and by osmotic pump. Drug levels in the tumor were found to be higher than those in the blood and kidney when the drug was delivered using the polymer implant. In contrast, for the other two delivery methods blood and kidney cisplatin levels were greater than those in the tumor. It has been previously shown that tumor response, in terms of growth delay, was greatest when drug was delivered by polymer implant and least when treatment was by osmotic pump.

Animals↗
PubMedDate not supplied

Nanoparticles for cellular drug delivery: mechanisms and factors influencing delivery.

Polymeric nanoparticles have demonstrated enormous potential as cellular drug delivery vehicles. Nanoparticles improve drug's stability as well as its availability and retention at the target intracellular site of action. Therapeutic efficacy of nanoparticles can be further enhanced by conjugating specific ligands to nanoparticle surface. Ligand conjugation can also be used to favorably modify the intracellular disposition of nanoparticles. A number of ligands are available for this purpose; use of a specific ligand depends on the target cell, the material used for nanoparticle formulation, and the chemistry available for ligand-nanoparticle conjugation. Cellular drug delivery using nanoparticles is also affected by clearance through the reticuloendothelial system. In this paper, we review the recent progress on our understanding of physicochemical factors that affect the cellular uptake of nanoparticles and the different cellular processes that could be exploited to enhance nanoparticle uptake into cells.

Cell Physiological Phenomena↗