Silibinin solubilization: combined effect of co-solvency and inclusion complex formation.

OBJECTIVE: Belonging to the class II drugs according to the biopharmaceutics classification system, silibinin (SLB) benefits from high permeability but suffers poor solubility that negatively affects the development of any delivery system. This research aimed to improve SLB solubility by combined use of co-solvency and complexation phenomena. METHODS: Solubility studies were performed using the phase solubility analysis according to the shake-flask method in the presence of ethanol and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a co-solvent and inclusion complexing agent, respectively. SLB release studies from chitosan nanoparticles were carried out in double-wall, diffusion cells using the optimized drug release medium. RESULTS: SLB solubility was mathematically optimized constraining to using the lowest concentrations of ethanol and HP-ß-CD. SLB solubility increased linearly with the increase of HP-ß-CD concentration. The solubility in PBS-ethanol mixtures followed a log-linear model. SLB solubility in the presence of the ethanol co-solvent and HP-ß-CD complexing agent was optimized by adopting a genetic algorithm suggesting the phosphate buffer saline solution supplemented by 6%v/v ethanol and 8 mM HP-ß-CD as an optimized medium. The optimized solution was examined to study SLB release from chitosan nanoparticles (4.5 ± 0.2% drug loading) at 37 °C under static conditions. The sigmoidal release profile of SLB from the particles indicated a combination of erosion and diffusion mechanisms governing drug release from the nanoparticles. CONCLUSION: SLB solubility in a buffered solution supplemented by ethanol co-solvent and HP-ß-CD complexing agent is a function of free drug present in the semi-aqueous media, the drug-ligand binary complex, and the drug/ligand/co-solvent ternary complex.

Nanophytosomes for enhancement of rutin efficacy in oral administration for diabetes treatment in streptozotocin-induced diabetic rats.

Rutin is a natural antioxidant compound with several therapeutic benefits. However, the application of this bioactive compound is limited due to its low stability and bioavailability. To overcome these limitations, this study aimed to encapsulate rutin into nanophytosomes (NPs) and evaluate the therapeutic potency of this nanocarrier in streptozotocin (STZ)-induced diabetic rats. The particle size, zeta potential, and encapsulation efficiency of the prepared NPs were 72.72 nm, -22 mV, and 93.7%, respectively. The in vivo study showed that the oral administration of rutin-loaded NPs (containing 25 mg rutin/kg per day) for 4 weeks was more effective than free rutin in the control of hyperglycemia and hyperlipidemia in the STZ-induced diabetic rats. Additionally, the administration of rutin-loaded NPs regulated the activities of liver marker enzymes and the levels of total hemoglobin and glycated hemoglobin in the diabetic rats. The antioxidant defenses in the diabetic rats were increased by the administration of rutin-loaded NPs more than free rutin. Moreover, the histopathological study showed that the administration of rutin-loaded NPs restored the diabetes-induced damages in kidney, liver, and pancreas. In conclusion, encapsulation of rutin with phytosomes is an effective technique to benefit from its therapeutic potential, especially to attenuate diabetic complications.

A Rapid Mercury Droplet Electrode Polarography Method for Determination of Blood Lead Level in Lead Poisoned People.

BACKGROUND: Lead is a hazardous heavy metal, which causes many problems in the human body. Unfortunately, recent reports showed that smugglers and opium sellers add lead to drugs during the production procedure in order to increase its weight and cost. PURPOSE: The aim of this study was development of a rapid and accurate method for measurement of blood lead levels (BLL) in the oral and inhaled opiate abuser people. METHODS: BLL in samples obtained from the oral and inhaled opium addicted patients referring to Sina Hospital in Tabriz, Iran, during 2017 was compared with healthy control group (N=15). The wet digestion method was used to prepare whole blood and Mercury Droplet Electrode Polarography (MDEP) method was utilized for measurement of the lead content of digested samples. RESULTS: Results showed that there were significant differences between the BLL of samples obtained from oral (17.12±74.61 µg/dL, p<0.0003) and inhaled (19.33±2.257 µg/dL, p<0.0001) opium addicted groups in comparison with healthy control group (4.669±0.3367 µg/dL). CONCLUSION: Based on the results of this study it was observed that BLL in opium addicted people needs to be measured as soon as possible. Furthermore, screening of blood lead concentrations in opium-addicted people with a rapid and accurate MDEP method is very necessary and important.

Mesenchymal Stem Cells: A New Generation of Therapeutic Agents as Vehicles in Gene Therapy.

In recent years, mesenchymal stem cells (MSCs) as a new tool for therapeutic gene delivery in clinics have attracted much attention. Their advantages cover longer lifespan, better isolation, and higher transfection efficiency and proliferation rate. MSCs are the preferred approach for cell-based therapies because of their in vitro self-renewal capacity, migrating especially to tumor tissues, as well as anti-inflammatory and immunomodulatory properties. Therefore, they have considerable efficiency in genetic engineering for future clinical applications in cancer gene therapy and other diseases. For improving therapeutic efficiency, targeted therapy of cancers can be achieved through the sustained release of therapeutic agents and functional gene expression induction to the intended tissues. The development of a new vector in gene therapy can improve the durability of a transgene expression. Also, the safety of the vector, if administered systemically, may resolve several problems, such as durability of expression and the host immune response. Currently, MSCs are prominent candidates as cell vehicles for both preclinical and clinical trials due to the secretion of therapeutic agents in several cancers. In the present study, we discuss the status of gene therapy in both viral and non-viral vectors along with their limitations. Throughout this study, the use of several nano-carriers for gene therapy is also investigated. Finally, we critically discuss the promising advantages of MSCs in targeted gene delivery, tumor inhibition and their utilization as the gene carriers in clinical situations.

Development of a Carrier Free Dry Powder Inhalation Formulation of Ketotifen for Pulmonary Drug Delivery.

BACKGROUND: Pulmonary drug delivery route is gaining much attention because it enables to target the active ingredients directly to lung both for local and systemic treatments, which maximize the therapeutic effect and minimize unwanted systemic toxicity. Dry powder inhaler (DPI) systems for asthma therapy have shown several merits to the other pulmonary delivery systems such as nebulizers and metered dose inhalers. PURPOSE: The present study aims to develop and optimize a DPI formulation for Ketotifen fumarate through spray drying technique. METHODS: Particles size and morphology, crystallinity, and drug-excipient interaction of fabricated DPI formulations were evaluated by scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier Transform Infrared Spectroscopy methods, respectively. The aerosolization indexes and aerodynamic properties of dry powders were determined by next generation impactor. The powder flowability was assessed by measuring the Hausner ratio and compressibility index. RESULTS: Among solvent systems, ethanol-water mixture produced the most desirable powder property for inhalation after spray drying. Although co-spray dried formulations with ammonium bicarbonate resulted in the porous structure, it was not beneficial for DPI formulations due to the interaction with Ketotifen. DSC and XRD experiments proved the amorphous structure of prepared powders, which were stable for 12 months. CONCLUSION: The results of this study demonstrate the potential of Ketotifen DPI formulation and pave a way to use it easily in an industrial scale.

Sensitization of MDA-MBA231 breast cancer cell to docetaxel by myricetin loaded into biocompatible lipid nanoparticles via sub-G1 cell cycle arrest mechanism.

The harmful dose-dependent side effects of chemotherapy drugs have caused the discovery of novel perspective to evaluate chemotherapy protocols. In this study, the potential application of Compritol was investigated as a major scaffold into nanostructured lipid careers to highlight myricetin efficiency in treatment of breast cancer cells along with codelivery of docetaxel (DXT). Characterization of myricetin-loaded NLCs was carried out by measuring the particle size and zeta potential, using the scanning electron microscopy. MTT, DAPI staining, flow cytometric, and RT-PCR (real-time) assays were used to recognize novel formulation behavior on cell cytotoxicity as well as recognizing molecular mechanism of formulation concerning apoptosis phenomenon. Myricetin-loaded NLCs reduced the cell viability from 50 ± 2.3 to 40 ± 1.3% (p < 0.05). Percentage of apoptosis improved with combination treatment of myricetin-loaded NLCs and DXT in the MDA-MBA231 breast cancer cells. Expression of antiapoptotic genes (survivin, Cyclin B1, and Mcl1) indicated a significant reduction in factor along with increment in proapoptotic factor Bax and Bid mRNA rates. Overall, our results represented that the NLC delivery system could be a promising strategy to enhance the effect of anticancer agents such as DXT on breast cancer.

Skin toxicity of topically applied nanoparticles.

Nowadays, nanoproducts have found numerous applications, allowing them to enter the human body in different ways. Skin is a major body organ that acts as the first-line barrier between the internal organs and external environment. Although the inhalation and ingestion of nanoparticles is more dangerous compared with skin exposure, there are noteworthy information gaps in skin exposure to nanoparticles that need much attention. Despite the few reviews in the literature on the cytotoxic effects of nanoparticles, no research has reviewed the clinical side effects of nanoparticles following topical admonition, including skin inflammation, skin cancer and genetic toxicity.

A multilayer hollow nanocarrier for pulmonary co-drug delivery of methotrexate and doxorubicin in the form of dry powder inhalation formulation.

Lung cancer is the number one cause of cancer deaths in the global population and remains difficult to treat mainly because of the absence of targeted drug delivery stages and restrictions related with delivery of drugs to deep lung tissues. The aim of the present study was to develop a noninvasive, patient-convenient formulation for the targeted delivery of chemotherapeutics to cancer cells located in the deep lung tissue. A PEGylated paramagnetic hollow-nanosphere was fabricated, fully characterized and used as a nanocarrier for pulmonary co-delivery of Doxorubicin (DOX) and Methotrexate (MTX). In first step, magnetic-silica nanoparticles were synthesized and then coated with amino/acrylate groups and derivatized with polyethylene glycol (PEG). Finally, silica was removed to provide hollow structured nanoparticles. The biocompatibility of blank carriers and the efficiency of MTX-DOX-loaded carriers were also approved by MTT assay and DAPI staining. The aerosolization performance of nanoparticles embedded microspheres were assessed by next generation impactor. The almost natural zeta potential and obvious decrease in silica content observed by EDX and removal of intense silica characteristic peak at FTIR analyses approved the successful removal of silica layer and preparation of hollow-nanospheres. The successful PEGylation of multilayer magnetic hollow-nanospheres catalyzed by boric acid was confirmed by presence of amide groups in FTIR spectra. The developed polymeric nanoparticle showed quite appropriate loading capacity for both DOX and MTX (48%) because of designing adequate negatively and positively charged sites for both drugs. The cytotoxicity assays proved the safety of blank nanoparticles and efficacy of drugs-loaded nanoparticles on lung cancer A549 cell lines. The developed dry powder inhalation formulation of nanoparticles showed appropriate aerosolization performance (fine particle fraction around 22%). It was concluded that these outcomes may open the potentials for efficient pulmonary co-delivery of MTX and DOX to the carcinogenic tissues.

Improvement of dermal delivery of tetracycline using vesicular nanostructures.

The objective of this investigation was to study the potential use of nanoliposomes and nanotransfersomes in dermal delivery of tetracycline hydrochloride (TC) for acne treatment. Vesicular nanostructures were prepared by thin film hydration method and evaluated for their size, zeta potential, morphology, and entrapment efficiency. Minimal inhibitory concentration values of TC-loaded vesicles were evaluated and compared with TC aqueous solution against Staphylococcus epidermis. In vitro drug release and ex vivo drug permeation through the excised rat skin were performed to assess drug delivery efficiency. Particle size, zeta potential, and entrapment efficiency of prepared nanoliposomes and nanotransfersomes were found to be 75 and 78 nm, 17 and 7 mV, and 45 and 55%, respectively. Antimicrobial analysis indicated that there was no difference between vesicular formulations and aqueous solution of TC. In vitro drug release study indicated that nanoliposomes could release TC 2.6 folds more than nanotransfersomes, and skin permeation study showed that the permeability of TC-loaded nanotransfersomes was 1.6 times higher than nanoliposomes which was also confirmed by fluorescence microscope imaging. These findings concluded that nanoliposomal and especially nanotransfersomal formulations could be proposed as the potential approach for better therapeutic performance of TC against acne.

A review on the role of lipid-based nanoparticles in medical diagnosis and imaging.

Molecular and diagnostic imaging has been recently a subject of intense research in the treatment of numerous diseases. In medical imaging, there are different modalities with unique strengths including MRI, ultrasound imaging, computed tomography, positron emission tomography and single photon emission computed tomography. These systems need specific contrast agents to achieve a suitable image with the best quality. Nanoparticles represent an innovative tool in imaging field research and diagnostics of various diseases, especially cancerous ones. Among the nanocarriers, lipid-based nanoparticles, such as nanostructured lipid carriers, solid lipid nanoparticles and liposomes, are the most used carriers in imaging because of having many advantageous properties. This review addresses advancements in different lipid-based nanoparticles as tools in medical diagnostic and imaging.

The effect of different coating materials on the prevention of powder bounce in the next generation impactor.

In the process of quality control of pulmonary drug delivery products, aerosolization efficiency is mainly determined using impactors, e.g. next generation impactor (NGI). However, particle bounce may interfere with the validity and accuracy of results due to the overestimation of the respirable fraction. It is suggested that the coating of impactor's stages may prevent the particle bounce. Therefore, coating materials may influence the results of the aerosolization indexes of pulmonary dosage forms. The aim of this study was to investigate if the aerosolization indices are affected differently by using the different coating materials. In this study, the effects of using different materials including Span® 85, Tween® 80, silicon® oil, glycerin and Brij® 35/glycerin mixture recommended for the coating of NGI stages on the aerosolization indices such as fine particle fraction, fine particle dose, mass median aerodynamic diameter, and geometric standard deviation of salbutamol emitted from a commercial metered dose inhaler (MDI), were assessed. Three statistically different results were obtained on using Tween® 80, Span® 85 and silicon oil, and glycerin and Brij®35/glycerin mixture. It can be concluded that the type of coating material influenced the aerosolization indices of the examined MDI in NGIs.

Attenuation of Morphine-Induced Tolerance and Dependence by Pretreatment with Cerebrolysin in Male rats.

BACKGROUND: Dependence and tolerance to morphine are major problems which limit its chronic clinical application. PURPOSE: This study was aimed to investigate the attenuation effect of Cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,), on the development of Morphine-induced dependence and tolerance. METHODS: Male Wistar rats were selected randomly and divided into different groups (n=8) including: a control group, groups received additive doses of morphine (5-25 mg/kg, ip, at an interval of 12 h until tolerance completion), and groups pretreated with Cerebrolysin (40, 80 and 160 mg/kg, ip, before morphine administration). Development of tolerance was assessed by tail-flick test and the attenuation effect of Cerebrolysin on morphine-induced dependence was evaluated after injection of naloxone (4 mg/kg, ip, 12 h after the morning dose of morphine). Seven distinct withdrawal signs including: jumping, rearing, genital grooming, abdominal writhing, wet dog shake and teeth grinding were recorded for 45 min and total withdrawal score (TWS) was calculated. RESULTS: Results showed that administration of Cerebrolysin could prolonged development (10 and 14 days in administration of 80 mg/kg and 160 mg/kg Cerebrolysin) and completion (4, 10 and 14 days in administration of 40, 80 and 160 mg/kg Cerebrolysin, respectively) of tolerance. Results also indicated that administration of Cerebrolysin (40, 80 and 160 mg/kg) could significantly decreased the TWS value (62±2, 77±4 and 85±6%, respectively). CONCLUSION: In conclusion, it was found that pretreatment with Cerebrolysin could attenuated morphine-induced tolerance and dependence.

Application of Spray Drying Technique for Flowability enhancement of Divalproex Sodium.

BACKGROUND: Tablets and capsules are the most accepted and widely used solid dosage forms in the medical therapy. Flow property of the powders is playing a key role in the various pharmaceutical fields especially in the fomulation of tablets and capsules. The high hygroscopic crystalline structure of anhydrous Divalproex sodium (DVX) makes it to be appear as waxy white flakes with almost no powder flowability which cause serious problems during the tabletting and capsule filling procedures. PURPOSE: The main objective of this study was to improve the flowability of DVX powder. METHODS: DVX was mixed with mannitol or lactos in different ratios, dissolved in water and differet binary mixtures of ethanol:water, and finally spray dried with different spray drying conditions. Particle size and powders morphology were assessed by Scanning Electron Microscopy (SEM). The poweder flowability was assessed by measurmet of Hausner ratio (HR), Carr's index (CI) and angle of repose (AOR) indexes. Furthermore, the content uniformity of DVX in spray-dried powders was determined by using a validated HPLC technique. RESULTS: The results showed that spray drying technique improved DVX flowability by forming spherical particles with narrow size distribution AOR value of DVX was decrease from not flowable to 36.1° in spray dried solid dispersion indicating the improvmet of powder flowability from very poor to fair/good condition. CONCLUSION: Findings suggest that the spray drying technique improves DVX flowability and may pave the way for improvement in the tabletting procedure of DVX.

Improvement of citral antimicrobial activity by incorporation into nanostructured lipid carriers: a potential application in food stuffs as a natural preservative.

At the present time, utilization of essential oils in food preservation to prevent bacterial and fungal growth and improve shelf life and safety of the food products has notably gained increased interest. The aim of the present study was to improve the antimicrobial efficacy of citral as a natural preservative using nanostructured lipid carriers (NLCs). Formulations of NLCs were characterized using particle size analysis and scanning electron microscopy methods. Possible citral-carrier interaction and citral encapsulation efficiency percent (EE%) were assessed by Fourier transform infrared (FTIR) spectroscopy and gas chromatography techniques, respectively. Antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of citral-loaded NLCs were evaluated and compared with the conventional citral emulsion against various gram-positive bacteria (Staphylococcus aureus, Bacillus cereus), gram-negative bacteria (Escherichia coli), and fungi (Candida albicans). Citral-loaded NLCs were spherically shaped nanosized (74.8 nm) particles with narrow size distribution, high EE% (99.84%), and appropriate physical stability during 90 days of storage period. FTIR spectra indicated the interaction between citral and formulation ingredients, which justified the obtained high EE% value. The MIC and MBC values of citral-loaded NLCs were lower than those of citral emulsion for all microorganisms. NLCs formulation showed remarkable capability of encapsulating essential oil and increasing antimicrobial properties to offer effective preservation in food industry.

Formulation of Menthol-Loaded Nanostructured Lipid Carriers to Enhance Its Antimicrobial Activity for Food Preservation.

Purpose: Due to the antimicrobial property, menthol have significant potential for food preservation and foodstuff shelf life improvement. Nevertheless, menthol instability, insolubility, and rapid crystallization in aqueous media make it unsuitable for used in food products. This work was aimed to prepare menthol-loaded nanostructured lipid carriers (NLCs) to enhance its antimicrobial activity. Methods: Morphology, particle size and size distribution, encapsulation efficiency percent (EE%), and physical stability of the optimized formulation, prepared by hot melt homogenization method, were characterized by scanning electron microscopy, particle size analyzing, gas chromatography, and X-ray diffraction (XRD) methods. Minimum inhibitory concentration and minimum bactericidal concentration of menthol-loaded NLCs were evaluated and compared with conventional menthol emulsion against various Gram-positive (Staphylococcus aureus, Bacillus cereus) and Gram-negative bacteria (Escherichia coli), as well as one fungus (Candida albicans). Results: Menthol-loaded NLCs were spherically shaped nanosized (115.6 nm) particles with narrow size distribution (PDI = 0.2), suitable menthol EE% (98.73%), and appropriate physical stability after 90 days of storage period. XRD results indicated that menthol was in the amorphous form in the nanoparticles matrix. Antibacterial assay results revealed that the menthol-loaded NLCs exhibited significantly higher in vitro antimicrobial property than conventional menthol emulsion. The results also indicated that menthol-loaded NLCs had better effect on fungi than bacteria, and furthermore, antibacterial efficiency on Gram-positive bacteria was higher than Gram-negative bacteria. Conclusion: In conclusion, NLCs could be a promising carrier for improvement of antimicrobial activity and preservation efficacy of essential oils in foodstuffs.

Nanoethosomal formulation of gammaoryzanol for skin-aging protection and wrinkle improvement: a histopathological study.

BACKGROUND: Free radical scavengers and antioxidants, with the main focus on enhanced targeting to the skin layers, can provide protection against skin ageing. OBJECTIVE: The aim of the present study was to prepare nanoethosomal formulation of gammaoryzanol (GO), a water insoluble antioxidant, for its dermal delivery to prevent skin aging. METHODS: Nanoethosomal formulation was prepared by a modified ethanol injection method and characterized by using laser light scattering, scanning electronic microscope (SEM) and X-ray diffraction (XRD) techniques. The effects of formulation parameters on nanoparticle size, encapsulation efficiency percent (EE%) and loading capacity percent (LC%) were investigated. Antioxidant activity of GO-loaded formulation was investigated in vitro using normal African green monkey kidney fibroblast cells (Vero). The effect of control and GO-loaded nanoethosomal formulation on superoxide dismutase (SOD) and malondialdehyde (MDA) content of rat skin was also probed. Furthermore, the effect of GO-loaded nanoethosomes on skin wrinkle improvement was studied by dermoscopic and histological examination on healthy humans and UV-irradiated rats, respectively. RESULTS: The optimized nanoethosomal formulation showed promising characteristics including narrow size distribution 0.17 ± 0.02, mean diameter of 98.9 ± 0.05 nm, EE% of 97.12 ± 3.62%, LC% of 13.87 ± 1.36% and zeta potential value of -15.1 ± 0.9 mV. The XRD results confirmed uniform drug dispersion in the nanoethosomes structure. In vitro and in vivo antioxidant studies confirmed the superior antioxidant effect of GO-loaded nanoethosomal formulation compared with control groups (blank nanoethosomes and GO suspension). CONCLUSIONS: Nanoethosomes was a promising carrier for dermal delivery of GO and consequently had superior anti-aging effect.

Histological evaluation of follicular delivery of arginine via nanostructured lipid carriers: a novel potential approach for the treatment of alopecia.

The use of lipidic nanoparticles can overcome the limitations of skin penetration of hydrophilic charged materials. Oleic acid as an ion pairing agent was used to enhance the encapsulation of positively charged arginine into lipophilic nanostructured lipid carrier (NLC). Histological study on the male hamsters was performed to assess the efficiency of drug delivery on hair growth. The accumulation of NLCs in the hair follicles was verified and in vivo studies showed more new hair follicle growth by utilizing arginine-loaded NLCs than arginine aqueous solution. It was concluded that employing ion pairing agent could enhance drug encapsulation into NLCs structure.

Dramatic improvement in dissolution rate of albendazole by a simple, one-step, industrially scalable technique.

Low solubility and dissolution rate are the primary challenges in the drug development which substantially impact the oral absorption and bioavailability of drugs. Due to the poor water solubility, Albendazole (ABZ) is poorly absorbed from the gastrointestinal tract and shows low oral bioavailability (5%) which is a major disadvantage for the systemic use of ABZ. To improve the solubility and dissolution rate of ABZ, different classes of hydrophilic excipients such as sugars (lactose, sucrose, and glucose), polyols (mannitol and sorbitol), ionic surfactant (sodium lauryl sulfate) and non-ionic surfactant (Cremophor A25) were co-spray dried with ABZ. The crystallinity changes in the processed drug were characterized by differential scanning calorimetry and X-Ray diffraction methods were used to interpret the enhanced solubility and dissolution rate of the drug. Results showed that the solubility and dissolution rate of ABZ were increased 1.8-2.6 folds and 3-25 folds, respectively. Unexpectedly, SLS decreased the solubility index of drug powder even lower than the unprocessed drug which was attributed to drug-SLS ionic interaction as depicted from Fourier transform infrared spectroscopy. It was concluded that by applying the facile, one-step, industrially scalable technique and the use of small amounts of excipient (only 4% of the formulation), a great improvement (21 folds) in dissolution rate of ABZ was achieved. This finding may be used in the pharmaceutical industries for the formulation of therapeutically efficient dosage forms of class II and IV drugs classified in biopharmaceutical classification system.

The Effect of Spacer Morphology on the Aerosolization Performance of Metered-Dose Inhalers.

PURPOSE: Respiratory drug delivery has been attracted great interest for the past decades, because of the high incidence of pulmonary diseases. However, despite its invaluable benefits, there are some major drawbacks in respiratory drug delivery, mainly due to the relatively high drug deposition in undesirable regions. One way to improve the efficiency of respiratory drug delivery through metered-dose inhalers (MDI) is placing a respiratory spacer between the inhaler exit and the mouth. The aim of this study was to assess the effect of type and shape of spacer on the aerosolization performance of MDIs. METHODS: A commercial Beclomethasone Dipropionate (BDP) MDI alone or equipped with two different spacer devices (roller and pear type) widely distributed in the world pharmaceutical market was used. The effect of spacers was evaluated by calculating aerosolization indexes such as fine particle fraction (FPF), mass median aerodynamic diameters (MMAD) and geometric standard deviation (GSD) using the next generation impactor. RESULTS: Although one of the spacers resulted in superior outcomes than the other one, but it was not statistically significant. CONCLUSION: The results confirmed that the type and shape of spacer did not substantially influence the aerosolization performance of MDIs.

The Effect of Particle Size on the Deposition of Solid Lipid Nanoparticles in Different Skin Layers: A Histological Study.

PURPOSE: In the present study the effect of particle size, as a substantial parameters in skin penetration, on the deposition depth and rate of SLNs in different layers of skin was explored. METHODS: SLNs in different particle size ranges (80, 333 and 971 nm) made of Precirol as solid lipid were prepared using hot melt homogenization technique and pigmented by Rhodamine B to be able to be tracked in the skin under inspection of fluorescent microscopy. After 0.5 h, 3 h, 6 h and 24 h of SLNs administration on rat skin, animals were sacrificed and exercised skins were sliced by a freeze microtome. SLNs were monitored in the skin structure under fluorescence microscope. RESULTS: The size of SLNs played a crucial role in the penetration to deep skin layers. The sub100 nm size range of SLNs showed the most promising skin penetration rate and depth mainly via hair follicles. CONCLUSION: The results of the present study indicated that the selection of an appropriate size of particles may be a valuable factor impacting the therapeutic outcomes of dermal drug administration.