Oseltamivir phosphate loaded pegylated-Eudragit nanoparticles for lung cancer therapy: Characterization, prolonged release, cytotoxicity profile, apoptosis pathways and in vivo anti-angiogenic effect by using CAM assay.

The target of the current investigation was the delivery of oseltamivir phosphate (OSE) into the lung adenocarcinoma tissues by means of designing nanosized, non-toxic and biocompatible pegylated Eudragit based NPs and investigating their anticancer and antiangiogenic activity. The rationale for this strategy is to provide a novel perspective to cancer treatment with OSE loaded pegylated ERS NPs under favor of smaller particle size, biocompatible feature, cationic characteristic, examining their selective effectiveness on lung cell lines (A549 lung cancer cell line and CCD-19Lu normal cell line) and examining antiangiogenic activity by in vivo CAM analysis. For this purpose, OSE encapsulated pegylated ERS based NPs were developed and investigated for zeta potential, particle size, encapsulation efficiency, morphology, DSC, FT-IR, 1H NMR analyses. In vitro release, cytotoxicity, determination apoptotic pathways and in vivo CAM assay were carried out. Considering characterizations, NPs showed smaller particle size, cationic zeta potential, relatively higher EE%, nearly spherical shape, amorphous matrix formation and prolonged release pattern (Peppas-Sahlin and Weibull model with Fickian and non-Fickian release mechanisms). Flow cytometry was used to assess the apoptotic pathways using the Annexin V-FITC/PI staining assay, FITC Active Caspase-3 staining assay, and mitochondrial membrane potential detection tests. Activations on caspase-3 pathways made us think that OSE loaded pegylated ERS NPs triggered to apoptosis using intrinsic pathway. As regards to the in vivo studies, OSE loaded pegylated ERS based NPs demonstrated strong and moderate antiangiogenic activity for ERS-OSE 2 and ERS-OSE 3, respectively. With its cationic character, smaller particle size, relative superior EE%, homogenous amorphous polymeric matrix constitution indicated using solid state tests, prolonged release manner, highly selective to the human lung adenocarcinoma cell lines, could trigger apoptosis intrinsically and effectively, possess good in vivo antiangiogenic activity, ERS-OSE 2 formulation is chosen as a promising candidate and a potent drug delivery system to treat lung cancer.

Spray dried nanospheres for inclusion complexes of cefpodoxime proxetil with ß-cyclodextrin, 2-hydroxypropyl-ß-cyclodextrin and methyl-ß-cyclodextrin: improved dissolution and enhanced antibacterial activity.

OBJECTIVE: The aim of the current research was the development hard cellulose capsules containing cefpodoxime proxetil (CEF) (BCS-Class II) encapsulated nanospheres of inclusion complexes with ß-CD, HP-ß-CD and M-ß-CD for efficient antibacterial therapy. SIGNIFICANCE: The reason for this phenomenon is to bring an innovative approach to effective oral antimicrobial therapy with hard cellulose capsules containing spray dried nanospheres of CEF with ß-CD, HP-ß-CD and M-ß-CD by means of increased solubility, dissolution rate and improved antibacterial efficiency with lower oral dose. METHODS: Phase solubility analyses was performed to evaluate the drug/CD interaction, involving the stoichiometry and apparent stability constant. Following the preparation of inclusion complexes by spray-drying method, complexes were characterized for physical, solid-state and microbiological analyses. In vitro dissolution from hard cellulose capsules containing CEF and CEF/ß-CD, CEF/HP-ß-CD and CEF/M-ß-CD complexes were performed. RESULTS: According to AL type phase solubility curves, complexes were formulated as 1:1 molar ratio. The solubility of pure CEF was determined as 0.241 ± 0.002 mg mL-1, the solubility of inclusion complexes increased solubility from 3 to 5 times. The strong host-guest interaction was confirmed for CEF/HP-ß-CD and CEF/M-ß-CD complexes with SEM, DSC, FT-IR and 1H-NMR analyses. Inclusion complexes were more efficient on bacterial cells (2-4 fold) than pure CEF both Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Hard-cellulose capsules filled with inclusion complexes exhibited significantly faster release than unprocessed CEF. CONCLUSION: Hard-cellulose capsules containing CEF/HP-ß-CD and CEF/M-ß-CD complexes appear to be superior alternative to commercially available CEF tablets for effective antibacterial therapy.

Development and characterization of lyophilized cefpodoxime proxetil-Pluronic® F127/polyvinylpyrrolidone K30 solid dispersions with improved dissolution and enhanced antibacterial activity.

The aim of this study was the development of hard-cellulose capsules containing cefpodoxime proxetil (CEF) (BCS Class II) loaded novel Pluronic® F127 (P127)/Polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) using ultrasonic probe induced solvent-lyophilization method for effective antibacterial treatment by means of improved saturated aqueous solubility, dissolution rate, reduced particle size, and wettability. SDs were evaluated for physical and solid-state analyses. The solubility of pure CEF was calculated as 0.269 ± 0.005 mg/mL, SDs formulated with P127/PVP exhibited increased solubility from 3.5- to 8-fold. Molecular distribution of CEF in SDs and formation of CEF loaded amorphous polymeric network were confirmed with morphological study, thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), and 1H-NMR studies. Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), and Klebsiella pneumoniae (ATCC 700603) were used to investigate the antibacterial effectiveness of the SDs. The minimum inhibitory concentration (MIC) values of the P127/PVP SDs were found 2-8 times lower than the pure CEF. All SDs from hard-cellulose capsules exhibited significantly faster release than unprocessed CEF. The profiles of SDs and reference were detected to be dissimilar according to difference (f1) and similarity factor (f2). Hard-cellulose capsules containing CEF loaded P127/PVP SDs appear to be feasible alternative to commercially available CEF tablets for effective antibacterial therapy at lowest dose.

Novel approaches to cancer therapy with ibuprofen-loaded Eudragit® RS 100 and/or octadecylamine-modified PLGA nanoparticles by assessment of their effects on apoptosis.

Objective: The purpose of this study was the design ibuprofen (IBU)-loaded unique Eudragit® RS 100 (ERS) and/or octadecylamine modified PLGA nanoparticles (NPs) for cancer treatment.Significance: The rational for this approach is to bring a new approach to cancer treatment with modification of IBU-loaded PLGA NPs with ERS and/or octadecylamine by means of smaller particle size (PS), cationic surface, biocompatible nature, and investigating their selective efficacy on lung cell lines (A549 lung cancer cell and CCD-19Lu normal cell line).Methods: IBU encapsulated PLGA-based NPs were prepared and characterized for physical and solid-state analyses. In vitro release, MTT, and determination of apoptotic pathways were performed.Results: Considering characterizations, B, C, E, F, H, and K formulations with higher EE%, smaller PS and encouraging higher zeta potential were chosen for further experiments were intended to enhance anticancer action and apoptotic behavior. Formulations were showed biphasic release profile with extended release manner (Korsmeyer-Peppas model with a diffusion-controlled mechanism). The NPs effect on lung cancer cells with high specificity and affinity was demonstrated by MTT study. It was found that the effect of IBU was increased 4-28 times over the pure form. Annexin V-FITC/PI staining method, FITC Active Caspase-3 staining method, and mitochondrial membrane potential detection analyses was performed to determine the apoptotic pathways by flow cytometry.Conclusion: E coded NP is selected as a promising candidate with its highly specific affinity for human lung adenocarcinoma cells and could induce cell death effectively and be a potent system to treat lung cancer.

In vitro/in vivo evaluation of gamma-aminobutyric acid-loadedN,N-dimethylacrylamide-based pegylated polymeric nanoparticles for brain delivery to treat epilepsy.

Objectives of this study were the delivery of gamma aminobutyric acid (GABA) into the brain by means of developing brain targeted, nanosized, non-toxic and biocompatible polymeric nanoparticles, and investigating their effectiveness in epilepsy. For this purpose, GABA conjugated N,N-dimethylacrylamide-based pegylated nanoparticles were designed and characterised for particle size, zeta potential, pH, morphology, DSC, XRD, FTIR, GABA quantification and in vitro release. Formulations showed smaller particle size, cationic zeta potential characteristic, possible GABA polymeric matrix interaction and prolonged release pattern. Brain responses were examined using epileptic rats. Both formulations prepared were found to increase latency of seizure, decrease ending time of convulsion, duration of severe convulsion and mortality rate significantly compared with GABA solution. When GABA concentration was measured in Stratum corsatum, there was no statistical difference between GABA solution and formulations. All findings suggested enhancement in all phases of seizures indicating efficient delivery of GABA into the brain via formulations.

Levocetirizine Dihydrochloride-Loaded Chitosan Nanoparticles: Formulation and In Vitro Evaluation.

OBJECTIVES: The aim of the present study was to formulate levocetirizine hydrochloride (LCD)-loaded chitosan nanoparticles at submicron level with high entrapment efficiency and prolonged effect for optimizing the plasma drug concentration enhancing bioavailability. MATERIALS AND METHODS: LCD was successfully incorporated into chitosan nanoparticles by spray drying for the purpose of oral application. In vitro characteristics were evaluated in detail. RESULTS: LCD was successfully loaded into the polymeric matrices by spray drying. Characterization of the nanoparticles including encapsulation efficiency, particle size, zeta potential, morphology, polydispersity index, solid-state characterizations, and LCD quantification by high performance liquid chromatography was performed. The release pattern of LCD from the nanoparticles was determined using a dialysis tube in simulated intestinal fluid (pH 6.8). In vitro release profiles indicated prolonged release of LCD from the nanoparticles that followed the Korsmeyer-Peppas kinetic model. CONCLUSION: Chitosan-based LCD-loaded polymeric nanoparticles appear to be a promising drug delivery system for the active agent.