Clozapine loaded nanostructured lipid carriers engineered for brain targeting via nose-to-brain delivery: Optimization and in vivo pharmacokinetic studies

2021 ◽  
pp. 102533
Author(s):  
Hetal P. Patel ◽  
Priyanshi A. Gandhi ◽  
Priyanka S. Chaudhari ◽  
Bhargavi V. Desai ◽  
Ditixa T. Desai ◽  
...  
Keyword(s):  
Nanostructured Lipid Carriers ◽  
Brain Targeting ◽  
Pharmacokinetic Studies ◽  
Brain Delivery

scholarly journals Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1059
Author(s):  
Saif Ahmad Khan ◽  
Saleha Rehman ◽  
Bushra Nabi ◽  
Ashif Iqubal ◽  
Nida Nehal ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Fold Increase ◽  
Pharmacokinetic Studies ◽  
Nanostructured Lipid Carrier ◽  
Brain Delivery ◽  
The Brain

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.

Appraisal of Nano-lipidic Astaxanthin cum Thermoreversible Gel and its Efficacy in Haloperidol Induced Parkinsonism

2021 ◽  
Vol 18 ◽  
Author(s):  
Deepika Gautam ◽  
Samipta Singh ◽  
Priyanka Maurya ◽  
Manjari Singh ◽  
Sapana Kushwaha ◽  
...  
Keyword(s):  
Average Particle Size ◽  
Radical Scavenging ◽  
Nanostructured Lipid Carriers ◽  
Neuronal Uptake ◽  
Pharmacokinetic Studies ◽  
Average Particle ◽  
In Situ Gel ◽  
Thermoreversible Gel

Background: Parkinsonism has a toxic cascade of neurodegeneration, with akinesia as a major manifestation. Some antioxidants have shown promise against the disease. Astaxanthin is a powerful antioxidant, demonstrates free radical scavenging, and is also a potential neuroprotective agent Objective: To formulate astaxanthin laden nanostructured lipid carriers based thermoreversible gel for better neuronal uptake and better neuronal efficacy. Methods: The method for fabricating astaxanthin-nanostructured lipid carriers (ATX-NLC) was melt-emulsification, and these were optimized using factorial design and further evaluated for diverse parameters. Neurotoxicity was induced in rats by haloperidol. The treated and non-treated rats were then witnessed for their behaviour. TBARs and GSH levels were also determined. Pharmacokinetics was studied via HPLC. Results: The average particle size (by DLS), entrapment efficiency and zeta potential of optimized ATX-NLC were 225.6 ± 3.04 nm, 65.91 ± 1.22 % and -52.64 mV respectively. Astaxanthin release (after 24 h in simulated nasal fluid) from optimized ATX-NLC was 92.5 ± 5.42 %. Its thermo-reversible nasal gel (ATX-NLC in-situ gel) was prepared using poloxamer-127. The obtained gel showed in-vivo betterment in the behaviour of animals when studied using rotarod and akinesia test. Pharmacokinetic studies showed better availability of astaxanthin in the brain on the rats treated with ATX-NLC in-situ gel as compared to those treated with ATX-in-situ gel. Conclusion: Astaxanthin loaded lipidic nanoparticulate gel can be a hopeful adjuvant therapy for Parkinsonism and holds scope for future studies.

Nanostructured lipid carriers-mediated brain delivery of carbamazepine for improved in vivo anticonvulsant and anxiolytic activity

2020 ◽  
Vol 577 ◽  
pp. 119033 ◽  
Author(s):  
Namrah Khan ◽  
Fawad Ali Shah ◽  
Isra Rana ◽  
Muhammad Mohsin Ansari ◽  
Fakhar ud Din ◽  
...  
Keyword(s):  
Anxiolytic Activity ◽  
Nanostructured Lipid Carriers ◽  
Brain Delivery

scholarly journals Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies

Drug Delivery ◽  
2017 ◽  
Vol 24 (1) ◽  
pp. 692-700 ◽  
Author(s):  
Sara Nageeb El-Helaly ◽  
Ahmed Abd Elbary ◽  
Mohamed A. Kassem ◽  
Mohamed A. El-Nabarawi
Keyword(s):  
Ex Vivo ◽  
Brain Targeting ◽  
Pharmacokinetic Studies

scholarly journals Encapsulated Escitalopram and Paroxetine Intranasal Co-Administration: In Vitro/In Vivo Evaluation

2021 ◽  
Vol 12 ◽  
Author(s):  
Soraia Silva ◽  
Joana Bicker ◽  
Carla Fonseca ◽  
Nuno R. Ferreira ◽  
Carla Vitorino ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Common Mental Disorder ◽  
Drug Loading ◽  
Pharmacokinetic Studies ◽  
Brain Delivery ◽  
In Vivo Evaluation ◽  
The Brain

Depression is a common mental disorder. Its treatment with selective serotonin reuptake inhibitors (SSRIs) is effective only in a fraction of patients, and pharmacoresistance is increasing steadily. Intranasal (IN) drug delivery to the brain stands out as a promising strategy to improve current therapeutic approaches by operating as a shuttle to overcome the blood–brain barrier. This work aimed to simultaneously administer escitalopram and paroxetine by IN route to mice. For this purpose, three nanostructured lipid carriers (NLC1, NLC2, and BorNLC) and one nanoemulsion (NE) were tested for drug loading. After their characterization, investigation of their impact on nasal cell viability and SSRI permeability assays were performed, using a human nasal RPMI 2650 cell line in air–liquid interface. In vitro assays demonstrated that NLCs, including borneol (BorNLC), significantly increased escitalopram permeability (p < 0.01) and paroxetine recovery values (p < 0.05) in relation to the other formulations and non-encapsulated drugs. IN and intravenous (IV) pharmacokinetic studies performed in vivo with a single dose of 2.38 mg/kg demonstrated similar results for escitalopram brain-to-plasma ratios. IN administrations delayed escitalopram peak concentrations in the brain for 15–60 min and no direct nose-to-brain delivery was detected. However, encapsulation with BorNLC considerably decreased escitalopram exposure in the lungs (124 μg min/g) compared with free escitalopram by IN (168 μg min/g) and IV (321 μg min/g) routes. Surprisingly, BorNLC IN instillation increased concentration levels of paroxetine in the brain by five times and accelerated brain drug delivery. Once again, lung exposure was considerably lower with BorNLC (AUCt = 0.433 μg min/g) than that with IV administration (AUCt = 1.01 μg min/g) and non-encapsulated IN formulation (AUCt = 2.82 μg min/g). Direct nose-to-brain delivery was observed for paroxetine IN administration with a direct transport percentage (DTP) of 56.9%. If encapsulated, it increases to 74.2%. These results clearly emphasize that nose-to-brain delivery and lung exposure depend on the formulation and on the characteristics of the drug under investigation. NLCs seem to be an advantageous strategy for nose-to-brain delivery of lipophilic molecules, since they reduce systemic and lung exposure, thereby decreasing adverse effects. For hydrophilic compounds, NLCs are particularly important to decrease lung exposure after IN administration.

scholarly journals Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 451 ◽  
Author(s):  
Nermin E. Eleraky ◽  
Mahmoud M. Omar ◽  
Hemat A. Mahmoud ◽  
Heba A. Abou-Taleb
Keyword(s):  
Drug Delivery ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Relative Bioavailability ◽  
Nanostructured Lipid Carriers ◽  
Brain Targeting ◽  
Pharmacokinetic Data ◽  
Average Size

The opposing effect of the blood–brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 42 full factorial design. The optimum formulation (NLC-1) consisted of; Compritol® 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer® 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, −10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.

scholarly journals ZIPRASIDONE HYDROCHLORIDE LOADED NANOSTRUCTURED LIPID CARRIERS (NLCS) FOR INTRANASAL DELIVERY: OPTIMIZATION AND IN VIVO STUDIES

2019 ◽  
pp. 31-41
Author(s):  
PRAVEEN SIVADASU ◽  
GOWDA D. V. ◽  
SIDDARAMAIAH H. ◽  
HEMALATHA S.
Keyword(s):  
Statistical Design ◽  
Fold Increase ◽  
In Vivo Studies ◽  
Brain Targeting ◽  
Intravenous Route ◽  
Pharmacokinetic Studies ◽  
Nanostructured Lipid Carrier ◽  
Nasal Route ◽  
Blood Brain

Objective: The present study was an attempt to systemically deliver the most desirable schizophrenia drug, ziprasidone hydrochloride (ZRS) via the intranasal route using nanostructured lipid carrier (NLC) approach. Methods: The desired ZRS loaded NLCs were developed using central composite statistical design and the developed formulation was monitored for improving ZRS bioavailability and their brain targeting efficacy. Results: Pharmacokinetic studies revealed a 10 fold increase (ZRS blood-brain ratio) for NLCs administered through nasal route (in comparison to intravenous route). Similarly, the concentration of ZRS (in the brain) delivered via nasal route exhibits 4 fold increment at all-time points. Conclusion: Therefore, the obtained results suggest a potential nose to brain transport of loaded ZRS by effective bypassing of the Blood-Brain Barrier (BBB).

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