Maham Rahimi

In vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled drug delivery

UNLABELLED Previously uncharacterized poly(N-isopropylacrylamide-acrylamide-allylamine)-coated magnetic nanoparticles (MNPs) were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Properties of these nanoparticles such as size, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. Spherical core-shell nanoparticles with a diameter of 100 nm showed significantly lower systemic toxicity than did bare MNPs, as well as doxorubicin encapsulation efficiency of 72%, and significantly higher doxorubicin release at 41°C compared with 37°C, demonstrating their temperature sensitivity. Released drugs were also active in destroying prostate cancer cells (JHU31). Furthermore, the nanoparticle uptake by JHU31 cells was dependent on dose and incubation time, reaching saturation at 500 μg/mL and 4 hours, respectively. In addition, magnetic resonance imaging capabilities of the particles were observed using agarose platforms containing cells incubated with nanoparticles. Future work includes investigation of targeting capability and effectiveness of these nanoparticles in vivo using animal models. FROM THE CLINICAL EDITOR In this paper, previously uncharacterized magnetic nanoparticles were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Various properties of these nanoparticles were evaluated in vitro for targeted drug delivery.

Development of multiple-layer polymeric particles for targeted and controlled drug delivery

UNLABELLED The purpose of this work was to develop multilayered particles consisting of a magnetic core and two encompassing shells made up of poly(N-isopropylacrylamide) (PNIPAAm) and poly(D,L-lactide-co-glycolide) (PLGA) for targeted and controlled drug delivery. Transmission electron microscopy confirmed that multilayered particles were obtained with PNIPAAm magnetic nanoparticles embedded within the PLGA shell. Factorial analysis studies also showed that the particle size was inversely proportional to the surfactant concentration and sonication power and directly proportional to the PLGA concentration. Drug-release results demonstrated that these multilayer particles produced an initial burst release and a subsequent sustained release of both bovine serum albumin (BSA) and curcumin loaded into the core and shell of the particle, respectively. BSA release was also affected by changes in temperature. In conclusion, our results indicate that the multilayered magnetic particles could be synthesized and used for targeted and controlled delivery of multiple drugs with different release mechanisms. FROM THE CLINICAL EDITOR Authors demonstrate the synthesis of multilayered particles consisting of a magnetic core and two encompassing shells made up of poly (N-isopropylacrylamide) (PNIPAAm) and poly(D, L-lactide-co-glycolide) (PLGA) for targeted and controlled drug delivery. The presented results indicate successful synthesis and application for targeted and controlled delivery of multiple drugs with different release mechanisms.

Epidemiology of burn injuries: Highlighting cultural and socio-demographic aspects

Burns are devastating injuries that disproportionately affect people in developing countries, including children. In addition to a high mortality rate, survivors are burdened with life-long physical and emotional scars. The etiology and nature of burn injuries varies significantly by country, and this chapter explores the predominant causes and patterns of burn injury in both the developing and industrialized worlds. Gender differences play a significant role in the risk of burn injuries, across a spectrum with a predominance of women injured in fires from cooking and heating fuels in the developing world and industrial accidents primarily affecting men in developed nations. Children are particularly vulnerable to burn injuries, accounting for almost 50% of all burn patients in some studies. A majority of pediatric burns are scald injuries usually affecting very young children below the age of 5 years, and we discuss the behavioral patterns underlying this finding. Finally, the elderly form a rapidly increasing proportion of the population in many countries, and are often burdened with comorbidities that are likely to pose significant challenges in burn care.

Cytocompatibility studies of an in situ photopolymerized thermoresponsive hydrogel nanoparticle system using human aortic smooth muscle cells.

We have been investigating thermoresponsive hydrogel nanoparticle composite networks to develop photopolymerized hydrogels to deliver drugs for prevention of restenosis after angioplasty. These composite systems can form a gel under physiological conditions and release drugs in response to temperature changes. Our novel system, consisting of poly(N-isopropylacrylamide) thermoresponsive nanoparticles, photo cross-linker poly(ethylene glycol) diacrylate, and UV photoinitiator, 2-hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone-1-one (Irgacure 2959), would be photopolymerized in situ in the presence of UV light. The focus of this study was to evaluate the effects of photoinitiator and UV exposure on human aortic smooth muscle cells (HASMCs). We found that the exposure to UV light did not significantly affect the cellular survival within doses required for photopolymerization. The photoinitiator was cytocompatible at low concentrations (< or = 0.015% w/v); however, cytotoxicity increased with increasing photoinitiator concentrations. In addition, free radicals formed in the presence of a photoinitiator and UV light caused significant levels of cell death. An antioxidant (free radical scavenger), ascorbic acid, added to the cell media, significantly improved relative cell survival but increased the hydrogel gelation time. Finally, HASMC survival when exposed to all potential cytotoxic components was also evaluated by exposing HASMCs to media incubated with our composite hydrogels. In summary, our studies show that the photoinitiator and free radicals are responsible for the cytotoxicity on HASMCs, and the addition of antioxidants can significantly reduce these harmful effects.

Dual-responsive polymer-coated iron oxide nanoparticles for drug delivery and imaging applications.

We reported the synthesis and characterization of dual-responsive poly(N-isopropylacrylamide-acrylamide-chitosan) (PAC)-coated magnetic nanoparticles (MNPs) for controlled and targeted drug delivery and imaging applications. The PAC-MNPs size was about 150nm with 70% iron mass content and excellent superparamagnetic properties. PAC-MNPs loaded with anti-cancer drug doxorubicin showed dual-responsive drug release characteristics with the maximum release of drugs at 40°C (∼78%) than at 37°C (∼33%) and at pH of 6 (∼55%) than at pH of 7.4 (∼28%) after 21 days. Further, the conjugation of prostate cancer-specific R11 peptides increased the uptake of PAC-MNPs by prostate cancer PC3 cells. The dose-dependent cellular uptake of the nanoparticles was also significantly increased with the presence of 1.3T magnetic field. The nanoparticles demonstrated cytocompatibility up to concentrations of 500μg/ml when incubated over a period of 24h with human dermal fibroblasts and normal prostate epithelial cells. Finally, pharmacokinetic studies indicated that doxorubicin-loaded PAC-MNPs caused significant prostate cancer cell death at 40°C than at 37°C, thereby confirming the temperature-dependent drug release kinetics and in vitro therapeutic efficacy. Future evaluation of in vivo therapeutic efficacy of targeted image-guided cancer therapy using R11-PAC-MNPs will reinforce a significant impact of the multifunctional PAC-MNPs on the future drug delivery systems.

Burns as Child Abuse: Risk Factors and Legal Issues in West Texas and Eastern New Mexico

The purpose of this study were to describe risk factors for child abuse from burns and examine prosecution and conviction rates after case discussions at a multidisciplinary conference Retrospective cohort study of all pediatric burns admitted between 2001 and 2006 was performed. Registry data on age, sex, mechanism, location, and size of burn were recorded. Registry data were verified against nursing documentation for accuracy. All cases were reviewed at the multidisciplinary “care conference” to gather insight from various perspectives to make a final determination of abuse or neglect. Bivariate and multivariate analysis was used to identify factors associated with child abuse. Prosecution rates were determined by contacting child protective services and district attorneys offices. A total of 457 children were included in the analysis. Most of the children were boys (70%) and were of Hispanic origin (57%), with 30% white and 10% black. Hundred cases were suspicious for abuse after review at care conference. Younger age was a significant risk factor (OR: 0.73, 95% CI: 0.65–0.82), with the mean age of abused children being 1 ¾ years compared with 5 ½ years for accidental injuries. Girls were at higher risk for abuse (OR: 1.76, 95% CI: 1.06–2.91).Torso injuries were significantly more common in abused children, an unusual finding possibly reflecting a different abuse pattern in infants compared with toddlers. Suspected abuse resulted in longer hospital stays (OR: 1.03, 95% CI: 1.01–1.07). Prosecution rates and conviction rates in the authors region are low, at only 26 and 11% of suspicious cases, respectively. Young age and female sex were positively correlated with child abuse. Prosecution and conviction rates are remarkably low, despite using a multidisciplinary care conference to review all cases and obtaining early involvement of child protective services and law enforcement.

Deep vein thrombosis: current status and nanotechnology advances.

Deep vein thrombosis (DVT) affects up to 2 million people in the United States, and worldwide incidence is 70 to 113 cases per 100,000 per year. Mortality from DVT is often due to subsequent pulmonary embolism (PE). Precise diagnosis and treatment is thereby essential for the management of DVT. DVT is diagnosed by a thorough history and physical examination followed by laboratory and diagnostic tests. The choice of laboratory and diagnostic test is dependent on clinical pretest probability. Available laboratory and diagnostic techniques mainly involve D-dimer test, ultrasound, venography, and magnetic resonance imaging. The latter two diagnostic tools require high doses of contrast agents including either radioactive or toxic materials. The available treatment options include lifestyle modifications, mechanical compression, anticoagulant therapy, inferior vena cava filter, and thrombolysis/thrombolectomy. All of these medical and surgical treatments have serious side effects including improper clot clearance and increased risk of hemorrhage occurrence. Therefore, research in this field has recently focused on the development of non-invasive and accurate diagnostics, such as ultrasound enhanced techniques and molecular imaging methods, to assess thrombus location and its treatment course. The frontier of nanomedicine also shows high prospects in tackling DVT with efficient targeted drug delivery. This review describes the pathology of DVT along with successive medical problems such as PE and features a detailed listing of various diagnostic and therapeutic modalities that have been in use and are under development.

Characterization of Polymer Coated Magnetic Nanoparticles for Targeted Treatment of Cancer

The objective of this project is to develop and characterize a targeted drug delivery vehicle capable of the controlled release of chemotherapy to treat malignant tumors. Our construct consists of a magnetic core with a thermosensitive polymer (N-isopropylacrylamide, NIPA) shell. The advantage of this system is that a magnetic field can be used for targeting the construct as well as to induce heat for hyperthermia treatment. Furthermore, the drug can be loaded into the NIPA layer and released when the temperature reaches its lower critical solution temperature (LCST). Drug release studies were used to characterize the thermoresponsive properties of the construct. Cellular uptake and cytotoxicity studies were also performed to determine in vitro behavior. Our NIPA-magnetic nanoparticle presents a unique and effective method of treating many cancers while reducing the deleterious effects associated with traditional drug delivery methods.

Chemokine gradient formation in microfluidic devices to investigate prostate cancer cell migration

Metastasis of cancer requires adhesion and migration of cells. The effect of chemokine gradient on prostate cancer cells (PCC) is not well understood. A poly-dimethylsiloxane (PDMS) microfluidic device that enables time-lapse study of cell migration is presented. Photolithography and soft lithography processes were used to fabricate the PDMS devices from SU-8 molds. The device has two inlets, a cell reservoir and an outlet channel with a depth of 100μm. The microfluidic device is configured to provide fluid mixing leading to a gradient across the outlet channel. The inlets allow for introduction of different chemokines at different concentrations and flow rates. The cell migration in the presence of chemokine gradient and flow rate can thus be monitored in a time-lapse fashion. The gradient formations at different flow rates over different lengths of time have been analyzed. Flow rates of 2, 3, 6, 8, 10, 20 μl/min at 5-minute intervals for over an hour were monitored to determine optimum flow rates and times required to produce desired gradient profiles. Results suggest that gradients formed at lower flow rates have less variation over time. Moreover, lower flow rates do not affect cell movement making observation of cell migration towards gradients possible. Higher flow rates have better gradient definition but cells tend to flow away with the fluid.

Clinical Outcomes of Obturator Canal Bypass

Objective: Infected aortofemoral grafts pose a formidable challenge with a significant risk of limb loss and high mortality. Despite successful reports of obturator canal bypass (OCB) for infected aortofemoral graft and complicated groins, the technique has not gained widespread use. We reviewed our experience with OCB and performed a systematic review of the literature. Methods: A retrospective review of patients who underwent OCB in our institution between 1995 and 2013 was conducted. Demographics of the patients, comorbidities, previous interventions, and postoperative and longer term related events were recorded. Outcomes were primary and secondary patency, limb salvage, and survival rates. For the literature review, all published series in the English language were identified through a PubMed database query. Results: Fifteen patients underwent 18 OCBs during the study period. Mean age was 59.6 ± 12 years, and 11 were men. Indications for surgery were chronic infection in 10 patients and acute bleeding in 5. Polytetrafluoroethylene was used in all cases. Mean clinical follow‐up was 57.7 ± 42.3 months (range, 7.4‐181). The 30‐day complications included three (16.7%) superficial wound infections without any cardiac events, stroke, or death. Midterm outcomes included five late deaths and one myocardial infarction. Regarding major adverse limb events, three patients underwent above‐knee amputation. Another procedure was required in 11 of the 18 limbs (61%) at a mean duration of 42 months for reoperation and 35 months for reintervention. One OCB (6%) became infected, requiring removal at 42 months. Primary, primary assisted, and secondary patency was 65%, 71%, and 88% at 24 months, respectively. Overall survival and limb salvage was 83% and 81% at 36 months, respectively. Conclusions: The OCB can be performed safely with minimal early morbidity and mortality in well‐selected patients with infections limited to one femoral anastomosis site. Limb salvage and overall mortality in this series are excellent and in agreement with the reported literature on OCB. Long‐term follow‐up is recommended because of a significant reoperation and reintervention rate.