Inhalable Microparticles for Pulmonary Drug Delivery
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Solution Overview
Problem
Current treatments for pulmonary tuberculosis, multi-drug resistant tuberculosis, MRSA pneumonias, and MSSA pneumonias face challenges such as poor bioavailability of drugs, systemic toxicity, and inadequate lung tissue penetration, leading to poor patient compliance and development of resistant strains.
Innovation Solution
A biodegradable, inhalable microparticle formulation comprising a compound obtained from Streptomyces species fermentation and a biodegradable lipid, with a drug-to-lipid ratio of 1:15 to 1:25, administered via inhalation or intratracheal instillation to directly target lung macrophages.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If oral dosing of antitubercular drugs is administered, then the treatment can reach the lungs, but the plasma half-life is poor and drug is cleared within hours
Solution Approach 1:
The patent uses inhalable microparticles as an intermediary delivery system that bypasses the oral route limitations. The microparticles are inhaled directly into the lungs, where they are taken up by alveolar macrophages, providing sustained drug release directly at the infection site and avoiding rapid plasma clearance.
Solution Approach 2:
The biodegradable microparticles provide self-sustained drug delivery through controlled release mechanisms. The particles gradually degrade in the lung environment, releasing the antitubercular drug over extended periods without requiring repeated dosing, thereby extending plasma half-life and improving treatment reliability.
2Reliability
If high doses of antitubercular drugs are administered, then treatment efficacy may improve, but dose-related adverse effects increase
Solution Approach 1:
The patent applies local quality by concentrating the drug delivery directly to the lungs through inhalation rather than systemic distribution. The microparticles target alveolar macrophages specifically, achieving high local drug concentrations at the infection site while minimizing systemic exposure and associated adverse effects.
Solution Approach 2:
The drug is segmented into individual microparticles that can be independently taken up by macrophages. This segmentation allows for controlled, sustained release of small amounts of drug over time, avoiding the need for high single doses and reducing peak-related toxicity.
3Reliability
If second line antitubercular drugs are used for MDRTB treatment, then resistance can be addressed, but bioavailability in the lungs is poor
Solution Approach 1:
The inhalable microparticles serve as an effective intermediary that overcomes the poor bioavailability issue of second-line drugs. By delivering the drugs directly to the lungs via inhalation and facilitating macrophage uptake, the system ensures adequate drug concentrations reach the infection site, making second-line agents effective for MDRTB treatment.
4Reliability
If vancomycin is administered for MRSA pneumonia, then bacterial infection can be treated, but lung tissue penetration is inadequate with only 20% of plasma concentrations
Solution Approach 1:
The microparticles act as an intermediary delivery vehicle that bypasses the poor tissue penetration limitation of vancomycin. By delivering the drug directly to alveolar macrophages through inhalation, the system achieves effective lung tissue concentrations that would otherwise be unattainable through conventional administration routes.
5Quantity of substance
If linezolid is administered for MRSA pneumonia, then good oral bioavailability is achieved, but gastrointestinal adverse effects and thrombocytopenia occur
Solution Approach 1:
Instead of administering the drug orally and relying on systemic distribution (which causes GI effects), the patent inverts the approach by delivering the drug directly to the lungs through inhalation. This bypasses the gastrointestinal tract entirely, eliminating GI adverse effects while maintaining effective drug delivery to the infection site.
Data Source
AI summary
The present invention relates to a biodegradable, inhalable microparticle formulation comprising a compound of formula I obtained by fermentation of a microorganism of the Streptomyces species (PM0626271/MTCC5447), as described in PCT application publication WO2011027290, and a biodegradable lipid for drug delivery wherein the ratio of drug (compound of formula I) to lipid is 1:15 to 1:25. The present invention also relates to the process for preparation of the formulation and to the method of treatment of pulmonary tuberculosis, multi drug resistant tuberculosis (MDRTB), methicillin resistant Staphylococcus aureus (MRSA) pneumonias and methicillin sensitive Staphylococcus aureus (MSSA) pneumonias by administering therapeutically effective amount of the formulation to a mammal in need thereof. The present invention further relates to a method of delivering the microparticle formulation to a mammal in need thereof, wherein the formulation is administered by inhalation or intratracheal instillation for pulmonary delivery.