Active-targeted Nanotherapy as Smart Cancer Treatment

Drug delivery systems (DDS) can be designed to improve the pharmacological and therapeutic properties of drugs. Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in infective organs or cells, relative to others. Cancer is one of the major causes of mortality worldwide and innovative methods for cancer therapy are urgently required. Nanoparticles (NPs), by using active targeting strategy, can enhance the intracellular concentration of drugs in cancerous cells while avoiding toxicity in normal cells. Nanoparticles with bioscience are being actively developed for in vivo tumor imaging, bimolecular profiling of cancer biomarkers, and targeted drug delivery. The advantages of the targeted release system are the reduction in the frequency of dosages taken by the patient, having a uniform effect of the drug, reduction of drug side effects, and reduced fluctuation in circulating drug levels. In this chapter, we focus on targeted drug delivery systems integrated from nanobiotechnology

Formulation an In Vitro Evaluation of Solid Lipid Nanoparticle Loaded with Doxorubicin for the Treatment of Lung Cancer

Introduction: Lung cancer is the most malignant cancer today. Doxorubicin, an anthracycline antibiotic, is a widely used antineoplastic agent. Despite the good efficacy of doxorubicin, cardiotoxicity is the serious side effect that follows the treatment. Additionally, anthracyclines are likely to cause alopecia and myelosuppression and oral ulcerations. This toxicity and non-specific distribution of the drug often results in chemotherapeutic failure. The focus should be made on efforts to kill cancer cells by more specific targeting while sparing normal cells. Solid lipid nanoparticle (SLN) delivery strategies of doxorubicin have been developed to minimize the exposure of drug to the normal tissues. Methods and Results: SLNs were prepared by the modified high shear homogenization (HSH) method. Lipid matrix was melted and doxorubicin was added to obtain a clear melting solution. After, double distilled water was heated. surfactant was added to the water. Next, the aqueous surfactant solution was added to the melted lipid. Then, the hot water-surfactants solution was poured into the hot lipid phase, and the HSH method was employed to produce the nanoemulsion, then cooled under the room temperature to obtain the SLNs. Doxorubicin loaded SLNs were prepared with a mean size of 210 nm, doxorubicin encapsulation of 71% and yield of 68%. higher release rate of doxorubicin was achieved at lower pH, with the present system. Because of the basic nature of doxorubicin (pKa = 8.3), it has higher solubility at lower pH. Conclusions: These SLNs had superior in vitro anti proliferation activity against the A549 cell line. Doxorubicin loaded SLNs in comparison with free drug exhibits better selectivity for target cells and the formulation was less toxic to normal lung cells than against malignant A549 cells. These observations suggest that present system offers an exciting mode of delivery to the lipophilic anticancer drugs

New surface-modified solid lipid nanoparticles using N-glutaryl phosphatidylethanolamine as the outer shell

Soheila Kashanian1, Abbas Hemati Azandaryani1, Katayoun Derakhshandeh2,3 1School of Chemistry, Nanoscience and Nanotechnology Research Center and Sensor and Biosensor Research Center, Razi University, 2Department of Pharmaceutics, Kermanshah University of Medical Sciences, 3Nanoscience and Technology Research Center School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran Background: Solid lipid nanoparticles (SLNs) are colloidal carrier systems which provide controlled-release profiles for many substances. In this study, we prepared aqueous dispersions of lipid nanoparticles using a modified, pH-sensitive derivative of phosphatidylethanolamine. Methods: SLNs were prepared using polysorbate 80 as the surfactant and tripalmitin glyceride and N-glutaryl phosphatidylethanolamine as the lipid components. Particle size, polydispersity index, and zeta potential were examined by photon correlation spectroscopy. Morphological evaluation was performed using scanning electron microscopy, atomic force microscopy, and differential scanning calorimetry. Results: Photon correlation spectroscopy revealed a particle hydrodynamic diameter of 165.8 nm and zeta potential of –41.6.0 mV for the drug-loaded nanoparticles. Atomic force microscopy investigation showed the nanoparticles to be 50–600 nm in length and 66.5 nm in height. Differential scanning calorimetry indicated that the majority of SLNs possessed less ordered arrangements of crystals compared with corresponding bulk lipids, which is favorable for improving drug-loading capacity. Drug-loading capacity and drug entrapment efficiency values for the SLNs were 25.32% and 94.32%, respectively. Conclusion: The SLNs prepared in this study were able to control the release of triamcinolone acetonide under acidic conditions. Keywords: solid lipid nanoparticles, high-shear homogenization, triamcinolone acetonide, tripalmitin, phosphatidylethanolamin

Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients

The purpose in this study was to investigate poly(ethylene glycol)-modified poly (d,l-lactide-co-glycolide) nanoparticles (PLGA-PEG-NPs) loading 9-nitrocamptothecin (9-NC) as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these potent agents undergo a rapid and reversible hydrolysis with the loss of antitumor activity. Previous researchers have shown that the encapsulation of this drug in PLGA nanoparticles could increase its stability and release profile. In this research we investigated PLGA-PEG nanoparticles and their effect on in vitro characteristics of this labile drug. 9-NC-PLGA-PEG nanoparticles with particle size within the range of 148.5 ± 30 nm were prepared by a nanoprecipitation method. The influence of four different independent variables (amount of polymer, percent of emulsifier, internal phase volume, and external phase volume) on nanoparticle drug-loading was studied. Differential scanning calorimetry and X-ray diffractometry were also evaluated for physical characterizing. The results of optimized formulation showed a narrow size distribution, suitable zeta potential (+1.84), and a drug loading of more than 45%. The in vitro drug release from PLGA-PEG NPs showed a sustained release pattern of up to 120 hours and comparing with PLGA-NPs had a significant decrease in initial burst effect. These experimental results indicate that PLGA-PEG-NPs (versus PLGA-NPs) have a better physicochemical characterization and can be developed as a drug carrier in order to treat different malignancies

Pharmacokinetic study of furosemide incorporated PLGA microspheres after oral administration to rat

Objective(s): The purpose of the current study was to assess the feasibility of microspheres from biocompatible polymer for oral bioavailability (BA) enhancement of potent sulfonamide- type loop diuretic- Furosemide - which used in the treatment of congestive heart failure, caused edema, cirrhosis, renal disease and as an adjunct in acute pulmonary edema. The comparatively poor and inconstant BA of furosemide, which occurs site-specifically in the stomach and upper small intestine, has been ascribed to the poor dissolution of furosemide. Materials and Methods: In attempt to enhance the drug BA, poly (dl-lactic-co-glycolic acid) (PLGA) microspheres of furosemide were obtained using solvent-evaporation method and the carrier characteristics were investigated subsequently. Results: The in vivo performance of optimum formulation was assessed by pharmacokinetic evaluation of drug after orally administration of free and loaded in microspheres to rats (4 mg/Kg). For this reason, the concentration of drug in plasma was measured by a new developed and sensitive method of HPLC. Acceptable drug loading and encapsulation efficiency of microspheres were obtained to be 70.43 and 85.21 %, respectively. Microspheres provided improved pharmacokinetic parameters (Cmax = 147.94 ng/ml, Tmax = 1.92 hr) in rats as compared with pure drug (Cmax = 75.69 ng/ml, Tmax = 1.5 hr). The obtained AUC of drug in microsphere was 10 fold higher than of the free drug. Conclusion: The results showed that the prepared microspheres successfully improved BA of the poorly water-soluble drug effectively

Clinical Features and Drug Characteristics of Patients with Generalized Fixed Drug Eruption in the West of Iran (2005–2014)

Background. Generalized fixed drug eruption is a specific variant of fixed drug eruption with multifocal lesions. Diagnosis of this drug reaction is straightforward, but occasionally recognition of the causative drug is not possible. This study was aimed at evaluating the clinical features and culprit drugs in generalized fixed drug eruptions in the west of Iran. Method. This cross-sectional study was carried out on 30 patients with criteria of generalized fixed drug eruption over 9 years. Demographic, clinical, and drug intake information were collected. Results. Out of 30 patients (17 females and 13 males) with the mean age of 26.67±10.21 years, 28 (93.3%) and 2 (6.7%) cases had plaque and bullous clinical presentation, respectively. Upper limbs were the most common (90%) site of involvement. The antibiotic group, especially cotrimoxazole (26.1%), was reported to be the most common offending drug, but the causative drug was not determined in 7 (23.3%) patients. Conclusion. Many cases of generalized fixed drug eruption firstly presented as limited lesions and led to generalized lesion due to repeated intake of the causative drug. No causative drug was found in some patients, which might be associated with concurrent intake of several drugs, multiple FDE, and peculiarity of the patch test