Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release

AbstractLupinifolin, a plant flavonoid, has been reported to possess various pharmacological effects. It most likely exerts low oral bioavailability because of poor water solubility. The objective of this study was to develop lipid nanocarriers as drug delivery systems to increase the gastrointestinal absorption of lupinifolin extracted from Albizia myriophylla. Three types of nanocarriers, lupinifolin-loaded solid lipid nanoparticles, lupinifolin-loaded nanostructured lipid carriers, and lupinifolin-loaded nanoemulsions, were prepared by an emulsification-sonication technique. All three types of nanocarriers loaded with lupinifolin, lupinifolin-loaded solid lipid nanoparticles, lupinifolin-loaded nanostructured lipid carriers, and lupinifolin-loaded nanoemulsions, were successfully synthesized. The lipid components chosen to formulate nanocarriers were tripalmitin and/or medium chain triglyceride. Physicochemical characterizations along with releasing profiles of lupinifolin-loaded lipid nanocarriers were compared. It was found that the best lipid nanocarrier for lupinifolin was lupinifolin-loaded nanostructured lipid carriers, which demonstrated the particle size of 151.5 ± 0.1 nm, monodispersity distribution with a polydispersity index of 0.24, negative surface charge at − 41.2 ± 0.7 mV, high encapsulation (99.3%), and high loading capacity (5.0%). The obtained lupinifolin-loaded nanostructured lipid carriers exhibited prolonged release in a simulated circulatory system but produced a low release in gastrointestinal conditions (3.7%). Intestinal permeability of the nanocarriers was further evaluated in everted intestinal sacs. The results from the ex vivo study indicated that lupinifolin-loaded nanostructured lipid carriers significantly increased the absorption of lupinifolin compared to the native form. In conclusion, lupinifolin-loaded lipid nanocarriers were successfully formulated as delivery systems to enhance its oral bioavailability. Further in vivo experiments are needed to validate the results from this study.

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Fabrication, Characterization, and In Vivo Evaluation of Famotidine Loaded Solid Lipid Nanoparticles for Boosting Oral Bioavailability

Journal of Nanomaterials ◽

10.1155/2017/7357150 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Muhammad Shafique ◽

Mir Azam Khan ◽

Waheed S. Khan ◽

Maqsood-ur-Rehman ◽

Waqar Ahmad ◽

...

Keyword(s):

Drug Release ◽

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Lipid Nanoparticles ◽

Fickian Diffusion ◽

Release Time ◽

Pharmacokinetic Studies ◽

Prolonged Release ◽

Solid Lipid

Famotidine as H2 receptor has antagonistic effects on gastric secretion. Unfortunately, its hydrophobic nature contributes to its variable and poor oral bioavailability. In the current study efforts are being made to fabricate famotidine loaded solid lipid nanoparticles with narrow size distribution. Prepared nanoformulations were pharmaceutically evaluated to confirm the desired boosted oral bioavailability. Famotidine loaded nanoformulation (FFSe-4) showed particle size 111.9±1.3 nm, polydispersity index 0.464±0.03, zeta potential −33.46±2 mV, entrapment efficiency 84±2.7%, and drug loading capacity 2.709±0.13%. Drug-excipients compatibility was confirmed by Fourier transformed infrared spectroscopy. Scanning electron microscopy confirmed spherical shaped, nanosized particles. Differential scanning calorimetry and powder X-ray diffractometry confirmed the change in crystalline nature. Prepared nanoformulation was more stable at refrigerated temperature. In vitro study showed that drug release time is proportional to drug pay load and followed zero order kinetics. Release exponent (n>0.5) confirmed non-Fickian-diffusion mechanism for drug release. In vivo pharmacokinetic studies showed 2.06-fold increase in oral bioavailability of famotidine dispersed in solid lipid nanoparticles compared to commercial product. These results authenticate solid lipid nanoparticles as drug delivery system and propose prolonged release with improved oral bioavailability for famotidine.

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Intestinal Permeability of Artesunate-Loaded Solid Lipid Nanoparticles Using the Everted Gut Method

Journal of Drug Delivery ◽

10.1155/2018/3021738 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 11

Author(s):

Wadzanayi L. Masiiwa ◽

Louis L. Gadaga

Keyword(s):

Drug Release ◽

Intestinal Permeability ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Burst Release ◽

Prolonged Release ◽

Average Particle ◽

Dissolution Profile ◽

Dilution Technique ◽

Solid Lipid

Background. Artesunate is one of the most potent, rapidly acting and therapeutically versatile antimalarial drugs. Its efficacy is hampered by poor aqueous solubility and stability resulting in low oral bioavailability. Recent efforts to nanoformulate artesunate have shown great potential of improving its dissolution profile and bioavailability. However, no study has yet been done to investigate the intestinal permeability of these nanoformulations, which is a critical determinant of systemic absorption. Objective of the Study. The main aim of the study was to determine the intestinal permeability of artesunate-loaded solid lipid nanoparticles (SLN). Method. The microemulsion dilution technique was used to fabricate artesunate-loaded solid lipid nanoparticles. In vitro drug release studies were performed at pH 1.2 and 6.8 using the dialysis membrane method. The everted gut sac method was used to assess the intestinal permeability of the prepared nanoparticles. Results. The average particle size was 1109 nm and the polydispersity index (PDI) was 0.082. The zeta potential was found to be −20.7 mV. The encapsulation efficiency of the solid lipid nanoparticles obtained was 51.7%. At both pH 1.2 and 6.8, pure artesunate was rapidly released within the first 30 mins while the SLN showed a biphasic release pattern with an initial burst release during the first hour followed by a prolonged release over time. The rate of drug release increased with increasing pH. The apparent permeability (Papp) of SLN was found to be greater (0.169 mg/cm2) as compared to that of pure artesunate (0.117 mg/cm2) at the end of the experiment. Conclusion. The results obtained in this study showed that the microemulsion dilution technique can be used to formulate artesunate solid lipid nanoparticles. The formulation exhibited a sustained drug release profile. The intestinal permeability of artesunate could be enhanced by the nanoformulation.

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Antinociceptive antibiotics-loaded into solid lipid nanoparticles of prolonged release: Measuring pharmacological efficiency and time span on chronic monoarthritis rats

PLoS ONE ◽

10.1371/journal.pone.0187473 ◽

2018 ◽

Vol 13 (4) ◽

pp. e0187473 ◽

Cited By ~ 4

Author(s):

Carlos Valdes ◽

Gonzalo Bustos ◽

Jose L. Martinez ◽

Claudio Laurido

Keyword(s):

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Time Span ◽

Prolonged Release ◽

Solid Lipid

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The Current Situation in Chemical Stabilization of Biological Materials

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100093912 ◽

1972 ◽

Vol 30 ◽

pp. 132-133

Author(s):

John H. Luft

Keyword(s):

Electron Microscopy ◽

Electron Microscope ◽

Osmium Tetroxide ◽

Molecular Level ◽

Cross Linking ◽

Chemical Stabilization ◽

Specimen Preparation ◽

Sufficient Condition ◽

Radio Telescopes

With information processing devices such as radio telescopes, microscopes or hi-fi systems, the quality of the output often is limited by distortion or noise introduced at the input stage of the device. This analogy can be extended usefully to specimen preparation for the electron microscope; fixation, which initiates the processing sequence, is the single most important step and, unfortunately, is the least well understood. Although there is an abundance of fixation mixtures recommended in the light microscopy literature, osmium tetroxide and glutaraldehyde are favored for electron microscopy. These fixatives react vigorously with proteins at the molecular level. There is clear evidence for the cross-linking of proteins both by osmium tetroxide and glutaraldehyde and cross-linking may be a necessary if not sufficient condition to define fixatives as a class.

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