Development of a Respirable, Sustained Release Microcarrier for 5-Fluorouracil II: In Vitro and In Vivo Optimization of Lipid Coated Nanoparticles

Hitzman, Cory J.; Elmquist, William F.; Wiedmann, Timothy S.

doi:10.1002/jps.20590

Cited by 44 publications

(29 citation statements)

References 29 publications

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“…10 The direct delivery of 5-FU to the lung as an aerosol could maximize the local concentration, while minimizing the concentration of 5-FU in the rest of the body. [11][12][13][14] For aerosol delivery of pharmaceuticals to the lung, a narrow size distribution of fine particles is necessary. 15 Several conventional methods are currently being used to produce fine powders, including milling, spray-drying, recrystallization using solvent evaporation, and liquid antisolvents.…”

Section: Introductionmentioning

confidence: 99%

Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

Kalantarian

Najafabadi²,

Haririan

et al. 2010

IJN

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This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction.

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Section: Introductionmentioning

confidence: 99%

Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

Kalantarian

Najafabadi²,

Haririan

et al. 2010

IJN

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“…5-FU SLNs prepared using phospholipids were found to effectively reduce MDA-MB-468 tumor growth [9]. As an inhalation therapy, 5-FU SLNs have been found effective in lung cancer [10,11]. Multiple emulsion-ultrasonication method has also been employed to prepare 5-FU, which was found to be a promising alternative for passive targeting therapeutic agents for curing primary lung carcinoma [12].…”

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confidence: 99%

In vitro anticancer evaluation of 5-fluorouracil lipid nanoparticles using B16F10 melanoma cell lines

Shenoy

Gude²,

Murthy

2013

Int Nano Lett

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The present study is aimed to investigate the formulation and in vitro anticancer activities of solid lipid nanoparticles (SLNs) of 5-fluorouracil (5-FU) prepared using glyceryl monostearate (GMS) and cetyl palmitate (CP) by hot homogenization method. The lipids were selected based on the partition coefficient of 5-FU in lipids. The lipid nanoparticles were optimized for process and formulation parameters. The optimized nanoparticles were characterized for their zeta potential, morphology, release kinetics, and anticancer activity. Higher entrapments were achieved using a combination of emulsifiers. The zeta potential of the optimized CP and GMS SLN formulation were −8.26 and −9.35 mV, respectively. Both the optimized formulations were spherical. The in vitro release studies of SLNs of both the lipid carriers followed Peppas-Korsenmeyer equation when carried out at pH 3.5 and 7.4. The chemosensitivity assay carried out in B16F10 cell lines revealed that CP SLNs had better cytotoxicity than 5-FU solution and GMS SLNs at 48 h of incubation. Subtoxic concentration of 5-FU-loaded CP SLNs (0.12 μg/mL) possessed comparable antimigrational activity, colony inhibition activity, and cytopathic as that of 5-FU solution effects. The results indicated that encapsulating 5-FU in CP would be a promising delivery system for delivering 5-FU.

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“…However, this concept contradicts the fact that, due to blood circulation in the lung 52,53 and the lymphatic circulation, drug concentrations have been found in the systemic circulation and surgically resected lymph nodes. 31,32,84,131,230,231,238 In addition, a high percentage of lymph nodes in the aerosol treatment groups did not show any metastasis in several studies, so it is possible that this route of administration destroys tumor cells and prevents them from trafficking from the primary subcutaneous tumor to the lungs and lymph nodes via the lymphatic system. 31,32,49,57 Nevertheless, in many of these studies, an additional intravenous chemotherapy regimen was administered, so clear conclusions cannot be drawn.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, an evaluation has to be made of whether inhaled chemotherapy is appropriate for early-stage lung cancer, or as neoadjuvant or adjuvant treatment. 57,60,61,230,231 Because lesions are of smaller size, drug deposition is not prevented by the large mass median diameter of the tumor. 131 Current drug delivery systems have demonstrated an ability to achieve sustained release locoregionally, but further improvement is welcomed.…”

Section: Resultsmentioning

confidence: 99%

“…60 Moreover, additional formulations of 5-FU with lipid-coated nanoparticles or difluoromethylornithine, an important enzyme in cell proliferation, were devised to achieve sustained drug release and enhance anticancer properties. 60,230,231 In these studies, previously presented for their inhalable system carriers with 5-FU, a step was made forward in using inhaled chemotherapy as an adjuvant treatment. Studies using taxanes either with liposome carriers, nanoparticles, polymeric micelles, or lipid nanocapsules provided evidence of an increased therapeutic index by prolonging regional action in the lung.…”

Section: Inhalation Studiesmentioning

confidence: 99%

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Inhaled chemotherapy in lung cancer: future concept of nanomedicine

Zarogoulidis

Chatzaki²,

Porpodis³

et al. 2012

IJN

168

160

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Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.

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Development of a Respirable, Sustained Release Microcarrier for 5-Fluorouracil II: In Vitro and In Vivo Optimization of Lipid Coated Nanoparticles

Cited by 44 publications

References 29 publications

Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

In vitro anticancer evaluation of 5-fluorouracil lipid nanoparticles using B16F10 melanoma cell lines

Inhaled chemotherapy in lung cancer: future concept of nanomedicine

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