Suitability of liposomal carriers for systemic delivery of risedronate using the pulmonary route

Abstract

Objective: This study aims at testing the hypothesis that reversed phase evaporation liposomes (REVs) are suitable for systemic delivery of an anti-osteporotic drug (risedronate sodium (RS)) via pulmonary nebulization.

Materials and methods: RS REVs were prepared using phospholipids and cholesterol with or without stearylamine, and were characterized for morphology, entrapment efficiency (EE%), in vitro release, particle size and aerosolization behavior from an actively vibrating mesh nebulizer. RS accumulation in rat bones following intra-tracheal administration of the selected formulation was assessed using a radiolabelling-based technique, and histological examination of rat lung tissue was performed to assess its safety.

Results: The EE% of RS REVs ranged from 8.8% to 58.96% depending on cholesterol molar ratio, phospholipid type and presence of stearylamine. RS REVs’ particle size ranged from 2.15 to 3.61?µm and were spherical and moderately polydisperse. Nebulization of the selected formulation showed an aerosol output of 85%, a fine particle fraction of 70.75% and a predicted alveolar deposition of 30.39%. The amount of radiolabelled RS deposited in rat bones after pulmonary administration was 20%, while being considerably safe on lung tissues.

Conclusion: Cationic REVs is a promising carrier for systemic delivery of RS for treatment of bone resorptive diseases.     

Production,characterisation, and in vitro nebulisation performance of budesonide-loaded PLA nanoparticles

Abstract

The aim of this study is to prepare a nanosuspension of budesonide for respiratory delivery using nebuliser by optimising its particle size and characterising its in vitro deposition behaviour. PLA (poly lactic acid)–budesonide nanosuspension (BNS) was prepared using high-pressure emulsification/solvent evaporation method. To optimise particle size, different parameters such as PLA concentration, sonication time, and amplitude were investigated. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscope (SEM) analyses were performed to characterise the prepared PLA–budesonide nanoparticles. The in vitro aerodynamic characteristics of the PLA–BNS using a jet nebuliser were estimated and compared with that of commercially available suspension formulation of budesonide.

Budesonide-loaded PLA nanoparticles with fine particle size (an average size of 224–360?nm), narrow size distribution, and spherical and smooth surface were prepared. The optimum condition for preparation of fine particle size for aerosolisation was found to be at PLA concentration of 1.2?mg/ml and amplitude of 70 for 75?s sonication time. The in vitro aerosolisation performance of PLA–BNS compared to that of commercial budesonide indicated that it has significantly (p?<?0.05) smaller mass median aerodynamic diameter (MMAD) value with an enhancement in fine particle fraction (FPF) value. Improving the in vitro deposition of budesonide, PLA–BNS could be considered as a promising alternative suspension formulation for deep lung delivery of the drug using nebuliser.     

Modeling the effect of sonication parameters on size and dispersion temperature of solid lipid nanoparticles (SLNs) by response surface methodology (RSM)

Abstract

The objective of this study was to evaluate the effect of sonication time and pulse frequency on average dispersion temperature (ART), particle size and zeta potential of solid lipid nanoparticles (SLNs). A two-factor, three-level response surface methodology (RSM) was used to optimize sonication time between 5 and 15?min and pulse frequency from 30 to 90%. SLNs made from stearyl alcohol (SA) and cetyl trimethylammonium bromide (CTAB) blend at 1:3 ratio were prepared by applying high-shear homogenization and sonication. Pulse frequency and time were found to have a significant effect on particle size and ART. The effect of sonication parameters on zeta potential, however, was insignificant. The optimal sonication parameters for preparing 100?nm SLNs made from a SA/CTAB blend was 60% pulse frequency at 40% power for 10?min. Optimized sonication parameters were then used to investigate the effect of lipid type on SLN size and zeta potential. The mean particle sizes of SLNs made with SA, cetyl palmitate, Precirol®, Dynasan118® and Compritol® were 98, 190, 350, 350 and 280?nm, respectively. In conclusion, pulse frequency and time were found to be critical for obtaining SLNs with desirable size, whereas the stability of the SLNs was dependent on their lipid content.     

Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo

Objective: To formulate and evaluate solid-reversed-micellar-solution (SRMS)-based solid lipid microparticles (SLMs) for intramuscular administration of gentamicin.

Methods: SRMS formulated with Phospholipon® 90G and Softisan® 154 were used to prepare gentamicin-loaded SLMs. Characterizations based on size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release of gentamicin from the SLMs was performed in phosphate buffer while in vivo release studies were conducted in rats.

Results: Maximum EE% of 90.0, 91.6 and 83.0% were obtained for SLMs formed with SRMS 1:1, 1:2 and 2:1, respectively. Stable, spherical and smooth SLMs of size range 9.80?±?1.46?µm to 33.30?±?6.42?µm were produced. The release of gentamicin in phosphate buffer varied widely with the lipid contents. Moreover, significant (p?<?0.05) amount of gentamicin was released in vivo from the SLMs.

Conclusion: SRMS-based SLMs would likely offer a reliable means of delivering gentamicin intramuscularly.     

Floating microspheres of carvedilol as gastro retentive drug delivery system: 32 full factorial design and in vitro evaluation

Abstract

Context: Designing a sustained release system for Carvedilol to increase its residence time in the stomach.

Objective: Preparation of floating microsphere by the emulsion solvent diffusion method, studying the effect of various process parameters and optimize the formulation using full factorial design.

Methods: Different microsphere formulations were prepared by varying the ratio ethanol:dichloromethane (1:0 to 1:1.5), ethyl cellulose:hydroxypropyl methyl cellulose and stirring speed (800–1600?rpm). The effect of these variables on particle size, encapsulation parameters, surface topography, in vitro floatability and drug release were evaluated.

Results: 3² full factorial design was used for the optimization of the formulation. Drug entrapment efficiency, particle size and in vitro drug release were dependent on concentration of ethyl cellulose and stirring speed. Microspheres remained buoyant for more than 10?h and showed sustained release of the drug.

Conclusion: Floating microspheres of Carvedilol with good floating ability and sustained release were developed.     

Testosterone solid lipid microparticles for transdermal drug delivery. Formulation and physicochemical characterization

Purpose: The main objective of the study was to formulate and characterize testosterone (TS) solid lipid microparticles (SLM) to be applied as a transdermal delivery system.

Methods: Testosterone SLMs were formulated using an emulsion melt homogenization method. Various types and concentrations of fatty materials, namely glyceryl monostearate (GM), glyceryl distearate (GD), stearic acid (SA) and glyceryl behanate (GB) were used. The formulations contained 2.5 or 5?mg TS?g^?1. Morphology, particle size, entrapment efficiency (EE), rheological properties and thermal behaviour of the prepared SLM were examined. In vitro release characteristics of TS from various prepared SLM were also evaluated over 24?h using a vertical Franz diffusion cell. In addition, the effect of storage and freeze-drying on particle size and release pattern of TS from the selected formulation was evaluated.

Results: The results indicated that the type of lipid affected the morphology and particle size of SLM. A relatively high drug percentage entrapment efficiency ranging from 80.7–95.7% was obtained. Rheological studies showed plastic flow characteristics of the prepared formulations. DSC examination revealed that TS existed in amorphous form in the prepared SLM. Release studies revealed the following rank order of TS permeation through cellophane membrane after application of various formulations: 5% GM?<?5% GD?<?5% SA?<?5% GB?<?2.5% GM?<?2.5% SA?<?10% GD?<?10% GB. The drug permeation through excised abdomen rat skin after application of 10% GB–2.5?mg TS?g^?1 SLM was lower than that permeated through cellophane membrane. Moreover, SLM containing 10% GB–2.5?mg TS?g^?1 stored at 5°C showed good stability as indicated by the release study and particle size analysis. Trehalose showed high potential as a cryoprotectant during freeze drying of the selected SLM formulation.

Conclusions: The developed TS SLM delivery system seemed to be promising as a TS transdermal delivery system.     

A novel high-pressure precipitation tandem homogenization technology for drug nanocrystals production – a case study with ursodeoxycholic acid

Abstract

To overcome the limitations of the conventional particle size reduction technologies, a novel combinative particle size reduction method for the effective production of homogeneous nanosuspensions was investigated. Ursodeoxycholic acid, a poorly soluble drug representative, was tried to prepare nanosuspension by homogenization technology and high-pressure precipitation tandem homogenization technology. It was shown that the combinative approach could significantly improve the particle size reduction effectiveness over conventional homogenization approach. The Box–Behnken design analysis for process optimization revealed that the acceptable UDCA-NS was obtained wherein the optimal values of A, B, C and D were 10%, 500?bar, 0.125 and 600?bar, respectively. SEM results demonstrated that no significant aggregation or crystals growth could be observed in the freeze-dried UDCA nanocrystals. The DSC and XRD results showed that UDCA remained in a crystalline state. Dissolution velocities of the freeze-dried UDCA-NS powder were distinctly superior compared to those of the crude powder and physical mixture. The high-pressure precipitation tandem homogenization technology can be a good choice for nanosuspension preparation of poorly soluble UDCA, due to high efficiency of particle size reduction.     

Nanogel for dermal application of the triterpenoids isolated from Ganoderma lucidum (GLT) for frostbite treatment

Abstract

Objective: The purpose of this study was to formulate stable Ganoderma lucidum (GLT) nanogels suitable for topical delivery with a view to improve the therapeutic effect for frostbite.

Methods: GLT nanosuspensions were formulated using the high-pressure homogenization technique and then suitably gelled for characterized. In order to confirm the advantages of GLT nanogel for dermal application, skin permeation studies in vitro and pharmacodynamic evaluation in vivo were studied and compared with GLT–carbopol gel.

Results: The particle size analysis and SEM studies revealed that GLT nanosuspensions were still stably kept their particle size after suitably gelled by carbopol preparation. The drug content, pH, and spreadability of the GLT nanogel was found to be 99.23?±?1.8%, 6.07?±?0.1, and 26.42 (g·cm)/s, which were within acceptable limits. In vitro permeation studies through rat skin indicated that the amount of GLT permeated through skin of GLT nanogel after 24?h was higher than GLT–carbopol gel, and GLT nanogel increased the accumulative amount of GLT in epidermis five times than GLT–carbopol gel. No oedema and erythema were observed after administration of GLT nanogel on the rabbits' skin. Pharmacodynamic study showed that GLT nanogel was more effective than GLT–carbopol gel in treatment of frostbite.

Conclusion: The GLT nanogel possess superior therapeutic effect for frostbite compared with the GLT–carbopol gel, which indicates that nanogels are eligible for the use as a suitable nanomedicine for dermal delivery of poorly soluble drugs such as GLT.     

In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments

Context: Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes.

Objective: To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN).

Materials and methods: In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer.

Results and discussion: The effect of independent variables was studied in two stages. First, the effect of drug–polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500?nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release.

Conclusion: This implant could be further evaluated for pharmacological activities.     

参白药效部位纳米混悬剂的剂型工艺优化及其升白作用的研究

目的 优化参白方有效部位纳米混悬剂的制备工艺,并开展纳米混悬剂的表征和升高白细胞的药效研究。方法 以参白方总多糖和总皂苷混合物为药物原料,在单因素考察的基础上,通过高压均质法,以稳定剂用量、均质压力、均质次数为影响因素,开展参白有效部位纳米混悬剂剂型工艺的正交优化和沉降稳定的观察,对制得的纳米混悬剂进行表征和升高白细胞的药效试验。结果 参白有效部位纳米混悬剂最优剂型工艺为：药物与大豆卵磷脂质量比为1:1.75,均质压力700 bar,均质次数14次。测得纳米混悬剂的粒径为（277.3±2.17）nm,PDI为0.185±0.018,Zeta电位为（-32.50±0.86）mV。给药7 d后,与模型组比较,给药7 d后纳米混悬剂高剂量组白细胞水平显著升高,给药15 d各剂量组白细胞水平显著升高（P＜0.05）。结论 参白有效部位纳米混悬剂的剂型优化工艺合理、可行,制剂粒径符合纳米要求,分散均匀且稳定,具有较好的升白作用,为有效部位组成的中药纳米混悬剂的新药研究提供有益的启示。     

Evaluation of process parameters involved in chitosan microsphere preparation by the o/w/o multiple emulsion method

Abstract

Chitosans are interesting biopolymers largely studied for applications in the medical and pharmaceutical fields. In this work, an o/w/o multiple emulsion technique was used for the preparation of hydrophobic drug loaded microspheres. Moreover, the influence of critical variables (concentration of acetic acid in the polymer solution and drug-polymer ratio) on microsphere morphology and drug content was evaluated. Two chitosans of different molecular weights and deacetylation degree were employed; ketoprofen, a non-steroidal anti-inflammatory drug, was chosen as the hydrophobic model drug. The multiple emulsion method produced well-formed microspheres with good yields. Acetic acid concentration in the polymeric solutions influenced particle size and drug content of the microspheres. The highest drug encapsulation efficiencies were obtained for the lowest theoretical drug/chitosan ratio.     

Influence of phenolic acids on the storage and digestion stability of curcumin emulsions based on soy protein-pectin-phenolic acids ternary nano-complexes

Abstract

Aim: To design novel emulsifiers with the ability to improve the storage and digestion stability of curcumin emulsions, besides to investigate the influence of phenolic acids types on the emulsify ability of soy protein-pectin-phenolic acids complexes obtained by ultrasonication.

Methods: The ternary complexes were characterised by particle size, morphology, zeta potential, X-ray diffraction, Fourier transform infra-red and fluorescence spectroscopy. Additionally, changes in droplet size, charge, and microstructure were monitored as quantitative stability index of curcumin emulsions.

Results: Phenolic acid types significantly affected the formation of ternary complexes. Soy protein-pectin-ferulic acid complex (S-P-F) stabilised curcumin emulsion had the best emulsifying property, followed by soy protein-pectin- ellagic acid (S-P-E), and soy protein-pectin-tannic acid complexes (S-P-T). Moreover, S-P-F emulsion was found to retain efficiently cucumin within 30?days storage (77.35%) and simulated gastrointestinal tract (64.09%).

Conclusion: Protein-polysaccharide-phenolic acids emulsions are effective oral delivery systems for hydrophobic bioactives.     

Curcumin-loaded mixed micelles: preparation,optimization, physicochemical properties and cytotoxicity in vitro

Abstract

Although curcumin (CUR) can inhibit proliferation and induce apoptosis of tumors, the poor water solubility restricted its clinical application. The aim of this study was to improve the aqueous solubility of CUR and make more favorable changes to bioactivity by preparing curcumin-loaded phospholipid-sodium deoxycholate-mixed micelles (CUR-PC-SDC-MMs). CUR-PC-SDC-MMs were prepared by the thin-film dispersion method. Based on the results of single factor exploration, the preparation technology was optimized using the central composite design-response surface methodology with drug loading and entrapment efficiency (EE%) as indicators. The images of transmission electron microscopy showed that the optimized CUR-PC-SDC-MMs were spherical and well dispersed. The average size of the mixed micelles was 66.5?nm, the zeta potential was about ?26.96?mV and critical micelle concentration was 0.0087?g/l. CUR was encapsulated in PC-SDC-MMs with loading capacity of 13.12%, EE% of 87.58%, and the solubility of CUR in water was 3.14?mg/ml. The release results in vitro showed that the mixed micelles presented sustained release behavior compared to the propylene glycol solution of CUR. The IC₅₀ values of CUR-loaded micelles and free drug in human breast carcinoma cell lines were 4.10?μg/ml and 6.93?µg/ml, respectively. It could be concluded from the above results that the CUR-PC-SDC-MMs system might serve as a promising nanocarrier to improve the solubility and bioactivity of CUR.     

Effect of drug physico-chemical properties on the efficiency of top-down process and characterization of nanosuspension

Introduction: The top-down approach is frequently used for drug nanocrystal production. A large number of review papers have referred to the top-down approach in terms of process parameters such as stabilizer selection. However, a very important factor, that is, the influence of drug properties, has been not addressed so far.

Areas covered: This review will first discuss different nanocrystal technologies in brief. The focus will be on reviewing the different drug properties such as solid state and particle morphology on the efficiency of particle size reduction during top-down processes. Furthermore, the drug properties in the final nanosuspensions are critical for drug dissolution velocity. Therefore, another focus is the characterization of drugs in obtained nanosuspension.

Expert opinion: Drug physical properties play an important role in the production efficiency. The combinative technologies using modified drugs could significantly improve the performances of top-down processes. However, further understanding of the drug millability and homogenization will still be needed. In addition, a carefully established characterization system for nansuspension is essential.     

Optimization of novel tocopheryl acetate nanoemulsions for parenteral delivery of curcumin for therapeutic intervention of sepsis

Objective: The objective of this study is to develop a nanostructured parenteral delivery system, laden with curcumin (CUR), for the therapeutic intervention of sepsis and associated pathologies.

Methods: Nanoemulsions were fabricated using sonication and speed homogenization. Size and zeta potential were evaluated by dynamic light scattering and transmission electron microscopy analysis. Pharmacodynamic and pharmacokinetic studies were performed on a rat model of lipopolysaccharide (LPS)-induced sepsis.

Results: The drug content of optimized nanoemulsion (F5) formulation (particle size 246 ± 08 nm, polydispersity index (PDI) of 0.120, zeta potential of ?41.1 ± 1.2 mV) was found to be 1.25 mg/ml. In vitro release studies demonstrated that F5 was able to sustain the release of CUR for up to 24 h. Minimal hemolysis and cellular toxicity demonstrated its suitability for intravenous administration. Significant reduction of inflammatory mediator levels was mediated through enhanced uptake by in RAW 264.7 and THP-1 in absence/presence of LPS. Nanoemulsion resulted in an improvement of plasma concentration (AUC_F5/AUC _CUR = 8.80) and tissue distribution of CUR in rats leading to a reduction in LPS-induced lung and liver injury due to less neutrophil migration, reduced TNF-α levels and oxidative stress (demonstrated by levels of lipid peroxides as well as carbonylated proteins) as confirmed by histopathological studies.

Conclusion: The findings suggest that the therapeutic performance (i.e., reduction in oxidative damage in tissues) of CUR can be enhanced by employing tocol acetate nanoemulsions (via improving pharmacokinetics and tissue distribution) as a platform for drug delivery in sepsis-induced organ injury.     

Formulation and Characterization of Immunoreactive Tetanus Toxoid Biodegradable Polymer Particles

Poly lactide-co-glycolide and polylactide polymer particles entrapping immunoreactive tetanus toxoid (TT) were prepared with a view to developing a single shot controlled release vaccine formulation. Denaturation of TT by dichloromethane (DCM) during primary emulsification stage of particle formulation was minimized by incorporation of an optimal amount of rat serum albumin (RSA) in the internal aqueous phase. Incorporation of RSA as a stabilizer during the primary emulsification stage of polymer particle formulation protected the immunoreactivity of TT, enhanced its encapsulation efficiency and also led to uniform polymer particle formation. Use of sonication, both during primary and secondary emulsification processes, resulted in formation of nanoparticles whereas microparticles were formed when the secondary emulsion was carried out by homogenization. Immunoreactive TT particles made from different polymers incorporating stabilizers released antigen continuously for more than four months in vitro. Single injection of both type of particles encapsulating stabilized TT elicited anti-TT antibody titers in rats for more than five months, which was higher than that obtained with TT injected in saline. Anti-TT antibody titers in vivo were in accordance with the in vitro release characteristics of immunoreactive TT from the particles. Immune responses with hydrophobic polymer particles were better than those made using hydrophilic polymers. These results indicate the importance of protecting the immunoreactivity of TT during formation of polymer particles for sustained and improved antibody response.     

Effects of borneol on the pharmacokinetics of 9-nitrocamptothecin encapsulated in PLGA nanoparticles with different size via oral administration

Context: Although nanocarriers provide promising potential for oral drug delivery, the delivery efficiency remains unsatisfactory and needs to be improved. Size is considered to be the most important characteristic of nanoparticles related to their oral absorption. Borneol has been proved to have the ability to enhance the penetration and transport of many drugs through various physical barriers.

Objective: To investigate the effect of the particle size and coadministration of borneol on the pharmacokinetics and bioavailability of entrapped drug in different size poly(lactic-co-glycolic acid) (PLGA) nanoparticles.

Materials and methods: 9-Nitrocamptothecin (9-NC)-loaded PLGA nanoparticles with three different range of size (50–100?nm, 100–200?nm, 200–300?nm) were prepared by emulsion solvent-evaporation method. The pharmacokinetic study in rats of these nanoparticles with borneol was carried out.

Results: The experiments showed that the encapsulation drug in nanoparticles with size below 200?nm could improve the oral bioavailability of 9-NC. The small size nanoparticles (50–100?nm) had a better improvement efficacy. As for borneol, it played a significant promotion effect only on the small nanoparticles. Moreover, there was no significant influence on the nanoparticles with size more than 100?nm.

Discussion and conclusion: The study indicated that both entrapping drug in nanoparticles with the size below 100?nm and coadministrating with borneol could enhance the gastrointestinal absorption of water insoluble drug. The combination of the two strategies provides a potential approach to improve the oral bioavailability of drug.     

Preparation and characterization of β-cyclodextrin and poly(acrylic acid) microspheres

Abstract

A method for the preparation of poly(acrylic acid) (PAA) microspheres cross-linked with beta-cyclodextrin (β-CD) is described. The method is based on a water-in-oil (w/o) emulsion solvent evaporation technique which facilitates a condensation reaction between PAA and β-CD. Aqueous solutions of PAA and β-CD were used as the dispersed phase and food grade olive oil was used as the continuous phase. The effect of homogenization speed (used in the preparation of the emulsion), phase volume ratio and cyclodextrin-polymer load on the particle size of the microspheres produced was investigated in a replicated factorial design. Microspheres were sized by light microscopy. The particle size of the microspheres was influenced by all three variables with two significant first order interactions between the variables being observed (homogenization speed with phase volume ratio and homogenization speed with load). A second order interaction between the three principal factors was also observed. Particle size ranged from 16 to 150m, depending on the production variables employed. The yield for the technique was 69.5 × 9.5%. Using selected conditions, microspheres of 15–25 pm size were prepared from a range of PAA with different weight average molecular weights (w). These particles were then characterized for β-CD, free carboxylic acid group content and residual oleic acid.     

Formulation,characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles

Abstract

Context: Galbanic acid (GBA) is a sesquiterpene coumarin with different medicinal properties and anticancer effects.

Objective: To improve the anticancer activities of GBA, in the current study, we aimed to fabricate GBA-loaded solid lipid nanoparticles (GBA-SLNs) and study their biological activities in vitro.

Materials and methods: Hot homogenization was used for preparation of GBA-SLNs. The encapsulation efficiency (EE) and drug loading (DL) and in vitro release were determined. MTT, DAPI, DNA fragmentation, comet, and Anexin V apoptosis assays were used to compare the anti-cell proliferation and genotoxicity properties of GBA and GBA-SLNs against A549 cells and HUVEC to detect apoptosis and DNA damage in the final concentration of 100?µM after 48?h treatment.

Results: Scanning electron microscopy (SEM) and particle size analysis showed spherical SLNs (92?nm), monodispersed distribution, and zeta potential of ?23.39?mV. High EE (>98%) and long-term in vitro release were achieved. The stability of GBA-SLNs in aqueous medium was approved after 3 months in terms of size and polydispersity index. GBA was able to inhibit A549 growth with an IC₅₀ value of 62?µM at 48?h. Although GBA-SLNs could also inhibit the growth rate of A549 cells, the effect is perceived after 48?h, as approved by the quantitative expression of Bcl-xL and Casp 9 genes, and also genotoxicity assays.

Conclusion: Long-term apoptotic effect of GBA-SLNs compared with GBA may be due to the accumulation of GBA-SLNs in the tumor site because of deviant tumor pathology. Our data confirmed that SLNs could be exploited for sustained lipophilic GBA delivery.     

Formulation,characterization and evaluation of rotavirus encapsulated PLA and PLGA particles for oral vaccination

Polylactide (PLA) and polylactide-co-glycolide (PLGA) particles entrapping rotavirus (strain SA11) were formulated using a solvent evaporation technique. To minimize denaturation of viral antigen during the emulsification process, serum albumin was used as a stabilizer. Use of NaHCO₃ and sucrose during the primary emulsification step resulted in uniform stabilized particles entrapping rotavirus. Sonication during the primary emulsion and homogenization during the secondary emulsion process resulted in particles of sizes 2–8 μm, whereas nanoparticles were formed when sonication was used during both primary and secondary emulsion processes. Scanning electron and atomic force microscopy showed uniform pores and roughness throughout the polymer particle surface. Single dose oral immunization with 20 μg of antigen entrapped in PLA particles elicited improved and long-lasting IgA and IgG antibody titer in comparison to the soluble antigen. The study shows results illustrating the usefulness of polymeric microparticles as a potential oral delivery system for rotavirus vaccine.