Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease

Uppuluri, Chandra Teja; Ravi, Punna Rao; Dalvi, Avantika

doi:10.1016/j.ijpharm.2021.120881

Cited by 38 publications

(23 citation statements)

References 29 publications

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“…Uppuluri et al developed SLNs containing piribedil, an anti-Parkinson’s disease drug, and then loaded optimized SLNs in a thermoresponsive methylcellulose in situ gel [ 27 ]. PK studies in rats showed that the SLN gel (IN) and SLN suspension (IN) increased the AUC 0–6h,brain by 4- and 3.1-fold (RB% = 404.5 and 312.6), respectively as compared with the drug suspension (IN).…”

Section: In Vivo Evaluations Of Sln and Nlc-based Formulations For No...mentioning

confidence: 99%

“…Several studies compared SLN and NLC gels (IN) and plain SLN and NLC suspensions (IN). A recent study compared a piribedil-loaded SLN suspension and piribedil-loaded SLN gel, and found the brain bioavailability (AUC 0–6h,brain ) and mean brain residence time (MRT brain ) of the SLN gel were 1.29- and 1.40-fold greater than those of the SLN suspension, respectively [ 27 ]. Furthermore, the DTE%, DTP%, logRDTE%, B% IN/IV , and RB% values of the SLN gel (IN) were 137.5, 27.29, 2.40, 145.3, and 404.5, higher than those of the SLN suspension (IN) (119.9, 16.59, 2.34, 112.3, and 312.6, respectively).…”

Section: Effects Of Gelling Systems and Surface Modifications Of Slns...mentioning

confidence: 99%

“…These findings indicate that the SLN gel (IN) better targeted brain than the SLN suspension (IN). Besides the longer nasal residence of gel (21.7 min versus 8 min), the use of thermoresponsive in situ gel with rapid gelation may have reduced the spread of formulation from the olfactory region to respiratory epithelium, and therefore increased drug transport via direct routes [ 27 ]. In another study, the occurrence of seizures in pentylenetetrazole-treated rats was lower for lorazepam-loaded NLC gel (IN) than a lorazepam-loaded NLC suspension (IN) [ 84 ].…”

Section: Effects Of Gelling Systems and Surface Modifications Of Slns...mentioning

confidence: 99%

“…In particular, formulations based on SLNs and NLCs provide effective nose-to-brain transport to improve drug bioavailability by increasing drug solubility, drug permeation, and stability, extending the drug action, and reducing enzymatic degradation. SLNs and NLCs can also be loaded into hydrogel systems [ 26 , 27 ] or coated with mucoadhesive polymers to improve these effects [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…Regarding free drugs (IN) and free drugs (IV) comparisons (Figure7b), the IN route had a higher AUC brain /AUC blood ratio in 14 of 19 cases. Five cases reported a higher AUC brain /AUC blood ratio for free drugs (IV), which were piribedil-loaded SLN gel[27], efavirenz-loaded NLCs[65], ropinirole-loaded anionic NLC gel[61], nicergoline-loaded NLCs[58], and phenytoin-loaded NLCs (of particle size < 50 nm)[36]. The AUC brain /AUC blood ratios of SLN and NLC-based formulations (IN) were always higher than those of free drug (IV) in same studies (Figure7c).The boxplots in Figure7dshow that log(AUC brain /AUC blood ) values generally followed the order: SLN and NLC-based formulations (IN) > free drugs (IN) > free drugs (IV).…”

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confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

Nguyen

Maeng

2022

Pharmaceutics

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Nose-to-brain drug delivery has been of great interest for the treatment of many central nervous system (CNS) diseases and psychiatric disorders over past decades. Several nasally administered formulations have been developed to circumvent the blood-brain barrier and directly deliver drugs to the CNS through the olfactory and trigeminal pathways. However, the nasal mucosa’s drug absorption is insufficient and the volume of the nasal cavity is small, which, in combination, make nose-to-brain drug delivery challenging. These problems could be minimized using formulations based on solid lipid nanoparticles (SLNs) or nanostructured lipid carriers (NLCs), which are effective nose-to-brain drug delivery systems that improve drug bioavailability by increasing drug solubility and permeation, extending drug action, and reducing enzymatic degradation. Various research groups have reported in vivo pharmacokinetics and pharmacodynamics of SLNs and NLCs nose-to-brain delivery systems. This review was undertaken to provide an overview of these studies and highlight research performed on SLN and NLC-based formulations aimed at improving the treatment of CNS diseases such neurodegenerative diseases, epilepsy, and schizophrenia. We discuss the efficacies and brain targeting efficiencies of these formulations based on considerations of their pharmacokinetic parameters and toxicities, point out some gaps in current knowledge, and propose future developmental targets.

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Section: In Vivo Evaluations Of Sln and Nlc-based Formulations For No...mentioning

confidence: 99%

Section: Effects Of Gelling Systems and Surface Modifications Of Slns...mentioning

confidence: 99%

Section: Effects Of Gelling Systems and Surface Modifications Of Slns...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

Nguyen

Maeng

2022

Pharmaceutics

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Lyotropic Liquid Crystalline Based Nasal Spray for Improved Parkinson's Treatment: Enhanced Superior Nasal Tract Deposition and Antioxidation Strategy

Xia,

Zhong,

Wei

et al. 2024

Adv Funct Materials

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The blood–brain barrier is one of the serious challenges in the treatment of Parkinson's disease (PD), which severely hinders the drug's brain bioavailability. In this study, a lyotropic liquid crystalline (LLC) based in situ gel nasal spray loaded with the first‐line drug Levodopa (LDA) for PD is developed to resolve this issue based on a nose‐to‐brain drug delivery approach. Specifically, the two key stages of LLC‐based in situ gel nasal spray, droplet deposition, and drug retention are tailored. By adjusting LLC's precursor solution's viscosity, the droplet deposition on the superior nasal tract can be increased by 18 times. Through nasal mucus‐triggered sol–gel transition, the LDA nasal cavity retention is prolonged by three times. The epigallocatechin gallate is incorporated into the LLC‐based in situ gel nasal spray to inhibit the autoxidation of LDA and alleviate the oxidative stress response in PD. The results show that the LLC‐based in situ gel nasal spray has a 26‐fold higher brain bioavailability of LDA compared to oral administration. The PD rats show a significant improvement in behavioral and cognitive disorders after administration. The LLC‐based in situ gel nasal spray is proved to work by reducing oxidative damage. This study is anticipated to offer a promising strategy for the clinical application of LDA.

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Lipid and Transcriptional Regulation in a Parkinson's Disease Mouse Model by Intranasal Vesicular and Hexosomal Plasmalogen‐Based Nanomedicines

Wu,

Wang,

Deng

et al. 2024

Adv Healthcare Materials

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Plasmalogens (vinyl‐ether phospholipids) are an emergent class of lipid drugs against various diseases involving neuro‐inflammation, oxidative stress, mitochondrial dysfunction, and altered lipid metabolism. They can activate neurotrophic and neuroprotective signaling pathways but low bioavailabilities limit their efficiency in curing neurodegeneration. Here we created liquid crystalline lipid nanoparticles (LNPs) for protection and non‐invasive intranasal delivery of purified scallop‐derived plasmalogens. Our in vivo results with a transgenic mouse Parkinson's disease (PD) model (characterized by motor impairments and α‐synuclein deposition) demonstrated the crucial importance of LNP composition, which determines the self‐assembled nanostructure type. Vesicle and hexosome nanostructures (characterized by SAXS) displayed different efficacy of the nanomedicine‐mediated recovery of motor function, lipid balance, and transcriptional regulation (e.g., reduced neuro‐inflammation and PD pathogenic gene expression). Intranasal vesicular and hexosomal plasmalogen‐based LNP treatment led to improvement of the behavioral PD symptoms and downregulation of the Il6, Il33, and Tnfa genes. Moreover, RNA‐sequencing and lipidomic analyses established a dramatic effect of hexosomal nanomedicines on PD amelioration, lipid metabolism, and the type and number of responsive transcripts that may be implicated in neuroregeneration.This article is protected by copyright. All rights reserved

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Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease

Cited by 38 publications

References 29 publications

Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

Lyotropic Liquid Crystalline Based Nasal Spray for Improved Parkinson's Treatment: Enhanced Superior Nasal Tract Deposition and Antioxidation Strategy

Lipid and Transcriptional Regulation in a Parkinson's Disease Mouse Model by Intranasal Vesicular and Hexosomal Plasmalogen‐Based Nanomedicines

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