Preparation of oxytocin liposomes modified by cell penetrating peptides and evaluation on brain targeting efficiency via intranasal delivery / 药学学报

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

Glyceryl behenate-based solid lipid nanoparticles as a carrier of haloperidol for nose to brain delivery: formulation development, in-vitro, and in-vivo evaluation

Abstract This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.

Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of

Pharmacokinetics and Brain Delivery of Citalopram Hydrobromide Thermosensitive Nasal Gel in Rats / 中国药学杂志

OBJECTIVE: To investigate the pharmacokinetics of citalopram hydrobromide(CTH)thermosensitive nasal gel and further evaluate its brain delivery in rats. METHODS: The concentrations of CTH in rat plasma and brain tissue were determined by HPLC method. With intragastric administration (ig) of CTH solution as control, CTH thermosensitive nasal gel was intranasally given to rats and the concentrations of CTH in plasma and brain tissues were then determined. Moreover, the main pharmacokinetic parameters of CTH in plasma and brain tissues such as tmax, ρmax,relative bioavailability (Fr) and drug targeting efficiency (DTE) were estimated. RESULTS: Main pharmacokinetic parameters of CTH following nasal and ig administration to rats such as tmax and ρmax were 5 and 45 min, 2 152.86 and 589.68 ng•mL-1 in plasma, and 5 and 45 min, 17 660.56 and 1 171.68 ng•g-1 in brain tissue, respectively. Finally, the Fr and DTE of CTH thermosensitive nasal gel were found to be 184.91% and 250.03%, respectively. CONCLUSION: CTH thermosensitive nasal gel may be an ideal non-oral new dosage form with many advantages such as rapid in vivo absorption, high bioavailability and obvious brain delivery characteristics.

Formulation and evaluation of olanzapine loaded chitosan nanoparticles for nose to brain targeting an in vitro and ex vivo toxicity study.

Olanzapine is an atypical antipsychotic drug shows low bioavailability due to extensive first pass metabolism and results in numerous side effects due to non targeted delivery. The present study was aimed to prepare and characterize olanzapine loaded chitosan nanoparticles for nose to brain targeting. The olanzapine loaded chitosan nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions. The formulated nanoparticles showed mean particle size, polydispersity index and zeta potential to be 183.1±8.42 nm, 0.122±0.08, +52.1±2.4 mV respectively. The entrapment efficiency and drug loading was found to be 72.42 ±3.65% and 26 .04± 2.12. In vitro drug release was showed a biphasic release pattern with initial burst release followed by sustained release of formulated nanoparticles. In vitro toxicity studies were carried out on RPMI 2650 human nasal epithelial cell line by MTT assay. The obtained result shows lower toxicity (high IC50 value) of nanoformulation as compared to free drug. Ex vivo histopathological studies were carried out by using excised goat nasal mucosa and the microscopic structure of nasal mucosa shows no significant harmful effects of formulated nanoparticles. These results illustrate that olanzapine loaded chitosan nanoparticles is a potential new delivery system for treatment of depressant when transported via olfactory nasal pathway to the brain.