Multilamellar-Multivesicular CBD Liposomes for Oral Bioavailability
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Solution Overview
Problem
Cannabinoids, particularly cannabidiol (CBD), exhibit low and variable bioavailability due to their lipophilic nature, leading to poor absorption from oral formulations and inconsistent plasma concentrations, which hinders their therapeutic potential and requires multiple daily administrations.
Innovation Solution
The development of multilamellar-multivesicular liposomes (MLV-MVVs) with a higher polydispersity index and larger size distribution, comprising phospholipids like DMPC and optionally cholesterol, to enhance CBD bioavailability and stability in the gastrointestinal tract.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional unilamellar liposomes are used for CBD delivery, then the formulation is simpler to manufacture, but the oral bioavailability remains low (6.49%) and absorption is poor
Solution Approach 1:
The liposome structure is segmented into multiple lamellae (bilayers) arranged in a multilamellar-multivesicular configuration. This segmentation creates multiple compartments for CBD encapsulation, increasing the total encapsulation capacity and providing multiple interfaces for drug release, thereby enhancing oral bioavailability from 6.49% to 82.9%.
Solution Approach 2:
The liposome employs a nested structure where multiple vesicular compartments are contained within concentric bilayers. The multilamellar architecture creates inner and outer aqueous compartments, each capable of harboring CBD, effectively nesting multiple drug reservoirs within a single liposomal vehicle to improve absorption.
2Ease of operation
If highly lipophilic CBD is delivered orally in solution, then the formulation is easier to administer, but CBD precipitates in the gastrointestinal tract resulting in slower absorption rate than elimination
Solution Approach 1:
The liposome acts as an intermediary carrier between the orally administered CBD and the gastrointestinal tract. The phospholipid bilayer structure solubilizes the highly lipophilic CBD, preventing precipitation in the aqueous GI environment while maintaining a controlled release profile that exceeds the elimination rate, thereby resolving the contradiction between ease of administration and absorption speed.
Solution Approach 2:
The formulation changes the physical state of CBD from a precipitating solution to a stabilized encapsulated form within the liposomal bilayer. This parameter change in drug delivery system architecture transforms the absorption kinetics, ensuring the absorption rate surpasses the elimination rate despite oral administration.
3Ease of operation
If oral formulations of cannabinoids are used, then the route of administration is simplest for patients, but the bioavailability is low (5-10% of administered dose) and requires multiple daily administrations
Solution Approach 1:
The CBD is pre-encapsulated within the multilamellar liposomal structure before administration, performing the solubilization and protection functions in advance. This preliminary action ensures that the CBD is already in an optimized delivery format that maintains stability through digestion and enables consistent high bioavailability (82.9%), eliminating the need for multiple daily doses.
Solution Approach 2:
The formulation uses a composite material system combining phospholipids, cholesterol, and CBD in a multilamellar architecture. This composite structure leverages the amphiphilic properties of phospholipids and the membrane-stabilizing effects of cholesterol to create a robust delivery vehicle that maintains consistent bioavailability through the gastrointestinal tract.
4Reliability
If multilamellar-multivesicular liposomes with higher polydispersity index are used, then the CBD bioavailability increases to 82.9%, but the manufacturing precision and size control become more difficult
Solution Approach 1:
The manufacturing process employs excessive action in terms of energy input (sonication, extrusion, or high-pressure homogenization) to drive the formation of multilamellar structures. This intense processing creates the desired complex multilamellar-multivesicular morphology with higher polydispersity that achieves 82.9% bioavailability, accepting reduced size uniformity as a trade-off for the enhanced therapeutic effect.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The proposed liposome formulation achieves improved oral bioavailability of CBD, reaching up to 82.9% in animal studies, reducing variability and increasing absorption rates compared to conventional unilamellar liposomes.
Implementation Method 1
Liposomes are formed especially from phospholipids, which contain hydrophilic and hydrophobic parts and thus have amphiphilic properties
Implementation Method 2
Cannabinoids are lipophilic and potentially acid-labile compounds. Because of their hydrophobic nature, cannabinoids are poorly absorbed systemically from oral dosage forms
Data Source
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AI summary
The present invention pertains to a liposome comprising cannabidiol (CBD), a phospholipid component and optionally a sterol component, wherein the liposome comprises more than one bilayer, to related mixtures of liposomes, processes for manufacturing, medical uses and compositions.