Delving into the Latest Updates on Cholesteryl-palmitate/Dipalmitoylphosphatidylcholine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Cholesteryl palmitate/colfosceril palmitate, Colfosceril-palmitate/cholesteryl-palmitate, Dipalmitoylphosphatidylcholine/cholesteryl-palmitate

+ [3]

Target-

Mechanism-

Therapeutic Areas

Otorhinolaryngologic Diseases

Active Indication-

Inactive Indication

Acute otitis media

Originator Organization

Otodyne, Inc.

Active Organization-

Inactive Organization

Eledon Pharmaceuticals, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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The appropriate design of experiments (DoE) could support post-approval lean-stability approaches. A three-factor three-level face-centered design was constructed to evaluate the long-term stability of gliclazide (GLZ) alginate-gelatin beads. The formulation variables were GLZ%(X₁), alginate:gelatin ratio(X₂), and glutaraldehyde%(X₃). The studied responses included GLZ release at predefined intervals in 0.1 N HCl (2 h) followed by phosphate buffer (pH 7.4). Model-dependent and independent approaches were utilized for comparison. DoE-model validation and reduction were implemented. All the studied formulations showed non-significant changes in the particle size (p > 0.05) and most of them showed similar release profiles before and after storage. The directions of the relationships between the factors' main effects and the responses (Y₁:Q_0.5_h, Y₂:Q_2h, and Y₃:Q_4h) remained unchanged after storage. The optimal factor settings based on the proposed optimization criteria were defined. The optimized formulations (OP-1 and OP-2) showed non-significant changes in the particle size after storage. The release profiles and kinetics of OP-1 and OP-2 remained unchanged after storage. No chemical change was indicated (FT-IR). DSC-thermograms of OP-1 indicated GLZ conversion to a more stable polymorph after storage. While OP-2 showed a change in GLZ crystallinity. The stored and fresh beads' surfaces after GLZ release were almost similar. DoE could be utilized to evaluate, optimize, and predict the effects of different formulation variables on the long-term stability of GLZ alginate-gelatin beads.

14 Jun 2024·Science Advances

Realveolarization with inhalable mucus-penetrating lipid nanoparticles for the treatment of pulmonary fibrosis in mice

Article

Author: Chen, Chen ; Zhao, Kun ; Liu, Ying ; Yang, Zhenmei ; Yue, Xiao ; Han, Maosen ; Sun, Peng ; Wang, Yan ; Li, Anning ; Han, Kun ; Tang, Chunwei ; Dong, Yuanmin ; Zhang, Jing ; Shi, Chongdeng ; Wang, Zhibin ; Zhang, Yulin ; Kong, Zhichao ; Zhu, Danqing ; Fu, Zhipeng ; Zhao, Xiaotian ; Jiang, Xinyi

The stemness loss–associated dysregeneration of impaired alveolar type 2 epithelial (AT2) cells abolishes the reversible therapy of idiopathic pulmonary fibrosis (IPF). We here report an inhalable mucus-penetrating lipid nanoparticle (LNP) for codelivering dual mRNAs, promoting realveolarization via restoring AT2 stemness for IPF treatment. Inhalable LNPs were first formulated with dipalmitoylphosphatidylcholine and our in-house–made ionizable lipids for high-efficiency pulmonary mucus penetration and codelivery of dual messenger RNAs (mRNAs), encoding cytochrome b5 reductase 3 and bone morphogenetic protein 4, respectively. After being inhaled in a bleomycin model, LNPs reverses the mitochondrial dysfunction through ameliorating nicotinamide adenine dinucleotide biosynthesis, which inhibits the accelerated senescence of AT2 cells. Concurrently, pathological epithelial remodeling and fibroblast activation induced by impaired AT2 cells are terminated, ultimately prompting alveolar regeneration. Our data demonstrated that the mRNA-LNP system exhibited high protein expression in lung epithelial cells, which markedly extricated the alveolar collapse and prolonged the survival of fibrosis mice, providing a clinically viable strategy against IPF.

01 Apr 2024·Molecular Pharmaceutics

Nebulization and In Vitro Upper Airway Deposition of Liposomal Carrier Systems

Article

Author: Mravec, Filip ; Bělka, Miloslav ; Malý, Milan ; Cejpek, Ondřej ; Kejíková, Jana ; Lízal, František ; Mišík, Ondrej ; Jugl, Adam

Liposomal carrier systems have emerged as a promising technology for pulmonary drug delivery. This study focuses on two selected liposomal systems, namely, dipalmitoylphosphatidylcholine stabilized by phosphatidic acid and cholesterol (DPPC-PA-Chol) and dipalmitoylphosphatidylcholine stabilized by polyethylene glycol and cholesterol (DPPC-PEG-Chol). First, the research investigates the stability of these liposomal systems during the atomization process using different kinds of nebulizers (air-jet, vibrating mesh, and ultrasonic). The study further explores the aerodynamic particle size distribution of the aerosol generated by the nebulizers. The nebulizer that demonstrated optimal stability and particle size was selected for more detailed investigation, including Andersen cascade impactor measurements, an assessment of the influence of flow rate and breathing profiles on aerosol particle size, and an in vitro deposition study on a realistic replica of the upper airways. The most suitable combination of a nebulizer and liposomal system was DPPC-PA-Chol nebulized by a Pari LC Sprint Star in terms of stability and particle size. The influence of the inspiration flow rate on the particle size was not very strong but was not negligible either (decrease of D_v50 by 1.34 μm with the flow rate increase from 8 to 60 L/min). A similar effect was observed for realistic transient inhalation. According to the in vitro deposition measurement, approximately 90% and 70% of the aerosol penetrated downstream of the trachea using the stationary flow rate and the realistic breathing profile, respectively. These data provide an image of the potential applicability of liposomal carrier systems for nebulizer therapy. Regional lung drug deposition is patient-specific; therefore, deposition results might vary for different airway geometries. However, deposition measurement with realistic boundary conditions (airway geometry, breathing profile) brings a more realistic image of the drug delivery by the selected technology. Our results show how much data from cascade impactor testing or estimates from the fine fraction concept differ from those of a more realistic case.

100 Deals associated with Cholesteryl-palmitate/Dipalmitoylphosphatidylcholine

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute otitis media	Phase 2	US	Eledon Pharmaceuticals, Inc.	21 Feb 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03818815 (Pubmed) Manual	Phase 2	Acute otitis media	103	amoxicillin-clavulanate+OP0201	(zcovqdbcce) = No clinically meaningful differences hekulwpzhx (xaqphqyroo )	Negative	01 Dec 2021
				amoxicillin-clavulanate+Placebo
NCT03818815 (CTgov)	Phase 2	Acute otitis media	103	OP0201+Amoxicillin-clavulanate	oyqmphpxfa(uzmdasmpzo) = apilcvrfcv dtvqmlseyg (xhaqrclcit, qljccfugdo - jkebbvtbfa) View more	-	11 Aug 2020
NCT03828149 (CTgov)	Phase 1	-	17	Drug:OP0201 (Drug: OP0201)	(dexefialcm) = tzlvoaxazb cpkxvhuiis (brychqozws, ejtqqeqwgd - aznvxgeqlr)	-	30 Dec 2019
				Drug: Placebo (Drug: Placebo)	(dexefialcm) = psizvlpzeu cpkxvhuiis (brychqozws, tjkqvhlpfk - wadfwjcxpc)
NCT03766373 (CTgov)	Phase 1	Acute otitis media \| Earache	24	Drug: OP0201 20mg (Drug: OP0201)	(wrrvjpgtdh) = olqnsuvxtq nhsxygzhsw (balcnizsxp, jctbelihxj - nluinvaqsx) View more	-	21 Nov 2019
				Drug: Placebo 0mg (Drug: Placebo)	(wrrvjpgtdh) = rzwlcyteyj nhsxygzhsw (balcnizsxp, kkvonxhehl - vmuftialsf) View more