Enhanced LEEPO: Liposome Encapsulation Efficiency Predictor & Optimizer

Overview

Enhanced LEEPO is an advanced computational tool for predicting and optimizing the encapsulation efficiency of hydrophilic drugs in liposomes. Based on the mathematical model developed by Xu et al. (2012), this software integrates multiple factors that affect encapsulation including media effects, lipid properties, preparation methods, and geometric considerations.

Key Features

• Media Effects Modeling: Incorporates buffer type and ionic strength effects on lipid molecular area
• Elliptical Geometry: Supports both spherical and elliptical (prolate/oblate) liposome geometries
• Lipid Database: Built-in properties for common lipids with temperature-dependent calculations
• Preparation Method Comparison: Analyzes different preparation techniques for optimal encapsulation
• Drug-Lipid Interaction Detection: Identifies potential interactions that may affect encapsulation
• Advanced Visualization: Size distribution, pie charts, and comparative plots
• Defect Optimization: Iteratively adjusts defect percentage to match experimental values

Installation

Prerequisites

pip install numpy pandas matplotlib scipy

Setup

1. Download the enhanced_leepo.py file
2. Ensure you have Python 3.6+ installed
3. Install the required dependencies

Usage

Basic Command

python enhanced_leepo.py mu sigma size_range defect thickness molecular_area concentration volume [expected_ee] [aspect_ratio] [lipid_composition] [buffer] [prep_method] [temperature] [drug_name]

Examples

Basic Run (Spherical Liposomes)

python enhanced_leepo.py 190.0 38.0 1000 0.23 5.2 0.45 140 5

With Optimization Target

python enhanced_leepo.py 190.0 38.0 1000 0.23 5.2 0.45 140 5 60.04

Using Lipid Database (set thickness and mol_area to 0)

python enhanced_leepo.py 190.0 38.0 1000 0.23 0 0 140 5 60.04 1.0 "DSPC:CHOLESTEROL:DPTAP=6:3:2" "HEPES_10mM"

With Elliptical Geometry (aspect_ratio = 1.5)

python enhanced_leepo.py 190.0 38.0 1000 0.23 5.2 0.45 140 5 60.04 1.5

Full Example with All Parameters

python enhanced_leepo.py 190.0 38.0 1000 0.23 0 0 140 5 60.04 1.0 "DSPC:CHOLESTEROL:DPTAP=6:3:2" "HEPES_10mM" "THIN_FILM_HYDRATION_EXTRUSION" 25.0 "TENOFOVIR"

Input Parameters

Parameter	Description	Unit	Example
mu	Mean particle size	nm	190.0
sigma	Standard deviation	nm	38.0
size_range	Maximum size for calculation	nm	1000
defect	Anticipated defect percentage	%	0.23
thickness	Bilayer thickness (0 to use from database)	nm	5.2
molecular_area	Lipid molecular area (0 to use from database)	nm²	0.45
concentration	Lipid molar concentration	mMol/L	140
volume	Total sample volume	ml	5
expected_ee	Expected/target encapsulation efficiency [optional]	%	60.04
aspect_ratio	Ratio for elliptical liposomes (>1: prolate, <1: oblate) [optional]	-	1.5
lipid_composition	Lipid ratio in format "LIPID1:LIPID2=RATIO1:RATIO2" [optional]	-	"DSPC:CHOLESTEROL:DPTAP=6:3:2"
buffer	Buffer/media name from database [optional]	-	"HEPES_10mM"
prep_method	Preparation method from database [optional]	-	"THIN_FILM_HYDRATION_EXTRUSION"
temperature	Experimental temperature [optional]	°C	25.0
drug_name	Drug from database for interaction detection [optional]	-	"TENOFOVIR"

Output

The program generates several outputs:

1. Terminal output with calculated parameters and encapsulation efficiency
2. Multiple plots saved to a LEEPO-plots folder:
   • Encapsulation efficiency pie charts
   • Size distribution
   • Comparison plots (if optimization is performed)
   • Preparation method comparison

Databases

Lipid Database

Includes properties for common lipids like DSPC, DPPC, DMPC, DSPG, DPPG, DMPG, DPPS, DPTAP, SOPC, and cholesterol.

Buffer Database

Includes common buffers and their effects on lipid molecular areas:

• DI_WATER
• HEPES_10mM, HEPES_20mM
• PHOSPHATE_10mM, PHOSPHATE_50mM, PHOSPHATE_100mM
• NaCl_5mM, NaCl_20mM

Preparation Methods

Supported methods with their characteristic parameters:

• THIN_FILM_HYDRATION
• THIN_FILM_HYDRATION_EXTRUSION
• REVERSE_PHASE_EVAPORATION
• SONICATION
• ETHANOL_INJECTION
• FREEZE_THAW

Drug Database

Information on common drugs and their expected interactions:

• TENOFOVIR
• CALCEIN
• SUCROSE
• HEMOGLOBIN
• 5,6-CF
• IODINE
• SOD

References

1. Xu, X., Khan, M. A., & Burgess, D. J. (2012). Predicting hydrophilic drug encapsulation inside unilamellar liposomes. International journal of pharmaceutics, 423(2), 410-418. https://doi.org/10.1016/j.ijpharm.2011.12.019