Calcium Phosphate Nanoparticles for Photodynamic Therapy

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Solution Overview

Problem

Current photodynamic therapy (PDT) formulations face challenges such as inappropriate solubility in physiological solutions, stability issues, long-term tissue retention, skin photo-toxicity, and ineffectiveness in targeting unhealthy areas, limiting their effectiveness in treating tumors and bacterial infections.

Innovation Solution

Development of calcium phosphate nanoparticle-based photosensitizer formulations, including stabilizers and hydrophobic or hydrophilic photosensitizers like porphyrins and phenazinium dyes, which provide improved solubility, stability, and targeting capabilities for PDT, using methods like continuous precipitation and layer-by-layer functionalization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional photosensitizer formulations are used, then photodynamic therapy can be performed, but they exhibit inappropriate solubility in physiological solutions and stability issues

Engineering Contradiction:

ImprovestabilityVSAvoidsolubility

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

Calcium phosphate nanoparticles serve as an intermediary carrier system that resolves the solubility-stability contradiction. The nanoparticles provide a solid support matrix that stabilizes photosensitizers while their surface properties enable solubility in physiological solutions. The patent demonstrates that calcium phosphate nanoparticles can carry both hydrophobic and hydrophilic photosensitizers, achieving enhanced storage stability and bioavailability simultaneously.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If conventional photosensitizer formulations are used, then photodynamic therapy can be performed, but they exhibit long-term tissue retention and skin photo-toxicity

Engineering Contradiction:

Improveside effectsVSAvoidtissue retention

Core Design Contradiction:

Object-affected harmful factorsVSDuration of action of stationary object

Solution Approach 1:

The patent applies parameter changes by modifying the physical and chemical properties of the photosensitizer through nanoparticle encapsulation. The calcium phosphate nanoparticle carrier changes the distribution, clearance, and retention parameters of the photosensitizer in biological systems. This results in reduced long-term tissue retention and decreased skin photo-toxicity while maintaining therapeutic efficacy at the target site.

Inventive Principle:

Principle #35Parameter changes

3Manufacturing precision

If conventional photosensitizer formulations are used, then photodynamic therapy can be performed, but they show ineffectiveness in targeting unhealthy areas

Engineering Contradiction:

Improvetargeting accuracyVSAvoidtherapeutic efficacy

Core Design Contradiction:

Manufacturing precisionVSProductivity

Solution Approach 1:

The calcium phosphate nanoparticle formulations exhibit local quality enhancement through passive targeting mechanisms. The nanoscale size and surface properties of the particles enable preferential accumulation in unhealthy tissues such as tumors and infected areas through enhanced permeability and retention effects. This localized concentration improves targeting accuracy and therapeutic efficacy while reducing off-target effects.

Inventive Principle:

Principle #3Local quality

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 calcium phosphate nanoparticle formulations offer enhanced storage stability, improved bioavailability, and effective targeting of tumor cells and bacteria, reducing side effects and increasing the efficacy of PDT treatments.

Implementation Method 1

calcium phosphate nanoparticle-based photosensitizer formulations... comprising a hydrophobic or hydrophilic photosensitizer, nanoparticulate calcium phosphate

Methodology Applied

Scientific EffectAdsorption: Adsorption

Implementation Method 2

methods like continuous precipitation

Methodology Applied

Scientific EffectPrecipitation: Precipitation

Data Source

PatentUS8956648B2Calciumphosphate-based nanoparticles as carrier-systems for photodynamic therapy

Publication Date: 2015.02.17 BIOLITEC PHARMA MARKETING

AI summary

The present invention provides pharmaceutical photosensitizer-loaded nanoparticle formulations and their methods of preparation for photodynamic therapy, comprising a hydrophobic or hydrophilic photosensitizer, nanoparticulate calcium phosphate and in certain cases auxiliary reagents such as stabilizers. The calcium phosphate-based nanoparticle formulations of the present invention provide excellent storage stability and therapeutically effective amounts of photosensitizer for intravenous or topical administration. In a preferred embodiment, tetrapyrrole derivatives such as porphyrins, chlorins and bacteriochlorins, are the preferred hydrophobic photosensitizers to be formulated in calcium phosphate nanoparticle formulations for photodynamic tumor therapy. Additionally, 5,10,15,20-tetrakis(4-phosphonooxyphenyl)porphine (pTPPP) is a preferred hydrophilic photosensitizer for photodynamic tumor therapy. In another preferred embodiment, hydrophilic cationic and anionic photosensitizers, especially those of the phenazinium, phenothiazinium and xanthenes series have been found to inactive pathogen bacteria and are the preferred photosensitizers to be formulated in calcium phosphate nanoparticle formulations for antibacterial photodynamic therapy. In another embodiment, photosensitizing nanoparticle formulations are useful to locate cells, tissues or bacteria by using fluorescence imaging methods.