製薬業界向け脂質ナノ粒子：前臨床と臨床の進歩

当レポートでは、がん、心臓血管、神経変性疾患など、さまざまな疾患の治療用デリバリーに使用するLNP開発の前臨床および臨床段階における研究開発の主な進展に焦点をあて、脂質ナノ粒子の使用における現在の研究と産業開発の詳細な分析を提供しています。また、ワクチン送達のためのmRNAキャリアとしてのLNPの使用については、産業界への導入と将来の展望に関する洞察を提供しています。さらに、LNPの生産と利用における課題と促進要因、重要な政策、イノベーション、主要な市場参入企業についての情報も提供しています。

目次

戦略的必須事項

• 成長がますます困難になっているのはなぜか？
• The Strategic Imperative 8（TM）
• 製薬業界における脂質ナノ粒子の研究開発の進歩に対する上位3つの戦略的必須事項の影響
• 成長機会がGrowth Pipeline Engine（TM）を促進
• 調査手法

成長機会分析

• 脂質ナノ粒子：概要と意義
• LNPは、核酸送達にはリポソームよりも適している
• 次世代の脂質ナノキャリアは、カプセル化と大規模生産において有望な特性を示す
• 第2世代のLNPにより、設計の柔軟性が向上し、安定性が向上
• 第一世代の脂質ナノ粒子は、化粧品、飲食品、栄養補助食品業界で広く使用されている
• 調査範囲
• セグメンテーション
• 成長促進要因
• 成長抑制要因

LNP：製剤、製造、および治療薬の提供

• LNPは脂質と安定剤の混合物を構成
• 承認されたLNP製剤は、異なる化学的および物理的特性の多様な貨物をカプセル化する
• 脂質と水相の混合比は、LNPのサイズとその捕捉効率を決定する
• 高圧ホモジナイゼーションは、LNPの大規模製造に適した選択肢である
• マイクロフルイディクスと超臨界流体技術により、粒子サイズと分布の制御が向上
• 配合技術は、サイズ、溶媒残留物、および分布を決定する上で重要な役割を果たす
• LNPのアクティブおよびパッシブターゲティングは、最小限の全身毒性で治療薬の細胞浸透の改善を示す
• mRNAワクチンと治療薬のin vivo安定性を改善するための脂質の合理的な設計が商品化を促進
• さまざまな疾患の治療にますます使用される脂質ベースのナノキャリア

LNP：研究開発の新興分野

• 抗体/リガンドとコンジュゲートされたLNPは、がんの標的化に対して高い特異性を示す
• 新しいリン脂質の組み合わせ、リンカー、およびコレステロールの代替品の設計と使用により、LNPのin vivo安定性、安全性、およびトランスフェクションが改善される
• 脂質とポリマーのハイブリッドLNPは、安定性とターゲティングを向上させ、相乗効果をもたらす
• LNP製剤のインライン検出と追跡により、生産時間を最小限に抑え、プロセスのフィードバック制御を可能にする
• LNPベースの治療法では、筋肉内および静脈内の送達経路が最も好まれる
• LNPの表面修飾と脂質および積荷の凍結乾燥により、長期保存の安定性が向上

情勢治療薬とワクチンの臨床、財務、イノベーションの展望

• 北米は、LNPベースの治療薬の商業的開発のために多額の資金を確保
• 民間資金は、ワクチンと免疫療法のための改善されたLNP製剤に焦点を当てている
• 耐熱性および標的LNPベースの治療薬の臨床試験への参入
• 製薬会社は、LNPの安定性、生分解性、製剤、費用対効果を革新する
• 脂質メーカーがAPI開発者と協力してLNPベースの治療法を活用
• LNPを使用した治療薬とワクチンの製剤は、臨床試験のさまざまな段階にある

知的財産分析

• 北米はLNPの特許出願で最高のシェアを保持
• 主要なLNPとmRNA企業が特許侵害をめぐって争う

成長機会領域

• 成長機会1：In-SilicoおよびAIベースの脂質組成予測
• 成長機会2：機能性を高めた安定したLNPの製剤化
• 成長機会3：自動化されたマイクロフルイディクスベースのLNP製造プラットフォーム
• 成長機会4：組織を標的とした送達のためのLNPの指向性開発

付録

次のステップ

Varied Lipid Composition, Improved Temperature Stability, and Efficient Manufacturing Drive Product Commercialization

In the last decade, nanomedicine and nanotechnology have helped unlock revolutionary therapeutic potential that has positively impacted healthcare. Among the different nanotechnology-based innovations, lipid-based nanoparticles such as liposomes and lipid nanoparticles (LNPs) show great promise across multiple therapies. Although the Food and Drug Administration (FDA) approved the use of liposomes for the delivery of cancer drug therapeutics in the early 90s, the recent breakthrough in use of LNPs for mRNA vaccine delivery for COVID-19 has created high interest in LNPs from pharmaceutical companies worldwide. Contract manufacturing of LNPs with diverse phospholipids of different surface charge and effective methods of stabilizing the lipid-based carriers using stabilizers such as cholesterols and emulsifiers to maintain size and drug-loading efficiency are the key focus areas in industrial R&D.

LNPs are chosen widely for drug/vaccine delivery due to their ease in formulation and high biocompatibility in comparison with other polymeric nanocarriers. LNPs have brough a radical change in the treatment of cancer therapy, ensuring improved drug delivery to the target site with minimal side effects. Importantly, LNPs can cross the blood-brain barrier (BBB) to improve drug delivery in treating brain tumors or neurodegenerative diseases. Apart from therapeutics, use of LNPs for the delivery of nucleic acids, such as pDNA, mRNA, and siRNA, has gained profound interest and potential in demonstrating high capabilities in viral vaccine delivery. The LNPs offer stability and protection to the mRNA, ensuring better efficacy and enhanced immune response. The last decade witnessed progress in LNPs used for treating complex diseases and as preventative vaccines; however, regulations of LNPs and their large-scale production for uniform size, shape, and product stability limit wide-scale adoption. The commercialization of LNPs for therapeutic and vaccine delivery holds major promise in transforming global health issues when supported by good manufacturing practices, regulations, and quality control analysis for better clinical translation.

This study offers an in-depth analysis of the current research and industrial developments in use of lipid-based nanoparticles. Focus areas include key advancements in R&D for the pre-clinical and clinical stages of LNP development for use in therapeutic delivery for different diseases such as cancer, cardiovascular, and neurodegenerative disorders. The use of LNPs as an mRNA carrier for vaccine delivery is discussed, providing insights on industrial adoption and future perspective. In addition, the research highlights the challenges and the drivers; important policies; innovations; and key market participants in LNP production and utilization.

This research answers the following questions:

• What are the current research advancements in use of LNPs for therapeutic and vaccine delivery?

• What is the current scenario and progress made in industrial manufacturing and adoption of LNPs?

• What are the advancements in optimizing stability, targeting ability, formulation, manufacturing, and storage of LNP-based therapeutics?

• What initiatives are industry participants undertaking to accelerate adoption?

• What are the expected outcomes in use of LNPs in the pharmaceutical sector, and how does it help to resolve global health challenges?

Table of Contents

Strategic Imperatives

• Why Is It Increasingly Difficult to Grow?The Strategic Imperative 8™: Factors Creating Pressure on Growth
• The Strategic Imperative 8™
• The Impact of the Top 3 Strategic Imperatives on the R&D Advances for Lipid Nanoparticles in the Pharmaceutical Industry
• Growth Opportunities Fuel the Growth Pipeline Engine™
• Research Methodology

Growth Opportunity Analysis

• Lipid-Based Nanoparticles: Overview and Significance
• LNPs Are Better Suited than Liposomes for Nucleic Acid Delivery
• Next-generation Lipid-based Nanocarriers Display Promising Attributes in Encapsulation and Large-scale Production
• Second-generation LNPs Offer Better Design Flexibility and Improved Stability
• Second-generation LNPs Offer Better Design Flexibility and Improved Stability (continued)
• First-generation Lipid-based Nanoparticles Are Used Widely in the Cosmetics, Food & Beverage, and Nutraceuticals Industries
• Research Scope
• Segmentation
• Growth Drivers
• Growth Restraints

LNPs: Formulation, Manufacturing, and Therapeutics Delivery

• LNPs Constitute a Mix of Lipids and Stabilizers
• Approved LNP Formulations Encapsulate Diverse Cargo of Different Chemical & Physical Properties
• Mixing Ratio of Lipids and Aqueous Phase Critically Determine the Size of LNPs and their Entrapment Efficiency
• High Pressure Homogenization Is the Preferred Choice for Large-scale Manufacturing of LNPs
• Microfluidics and Super Critical Fluid Technology Offer Improved Control over Particle Size and Distribution
• Formulation Techniques Play a Critical Role in Determining Size, Solvent Residue, and Distribution
• Active and Passive Targeting of LNPs Exhibit Improved Cellular Penetration of Therapeutics with Minimal Systemic Toxicity
• Rational Design of Lipids for Improved In Vivo Stability of mRNA Vaccines and Therapeutics Drives Commercialization
• Lipid-based Nanocarriers Increasingly Used in the Treatment of Various Diseases

LNP: Emerging Areas of R&D

• LNPs Conjugated with Antibody/Ligands Exhibit High Specificity for Cancer Targeting
• Design and Use of New Phospholipid Combinations, Linkers, and Cholesterol Alternatives Improve In Vivo Stability, Safety, and Transfection of LNPs
• Lipid and Polymer Hybrid LNPs offer Synergistic Benefits with Improved Stability and Targeting
• In-line Detection and Tracking of LNPs Formulation Minimizes Production Time and Enables Process Feedback Control
• Intramuscular and Intravenous Routes of Delivery Are Most Preferred for LNP-based Therapeutics
• Surface Modification of LNPs and Lyophilization of Lipids and Cargo Exhibit Improved Stability for Long-term Storage

Clinical, Financial, and Innovation Landscape of LNPs Therapeutics and Vaccines

• North America Secures High Funding for Commercial Development of LNP-based Therapeutics
• Private Funding Focuses on Improved LNP Formulations for Vaccines and Immunotherapeutics
• Entry of Thermostable and Targeted LNPs-based Therapeutics into Clinical Trials
• Pharmaceutical Companies Innovate in the Stability, Biodegradation, Formulation, and Cost-Effectiveness of LNPs
• Lipid Manufacturers Collaborate with API Developers to Leverage LNP-based Therapeutics
• Therapeutic and Vaccine Formulations Using LNPs Are in Different Phases of Clinical Trial

Intellectual Property Analysis

• North America Holds Highest Share of Patent Filings for LNPs
• Leading LNPs and mRNA Players Battle on Patent Infringement

Growth Opportunity Universe

• Growth Opportunity 1: In-silico and AI-based Lipid Composition Prediction
• Growth Opportunity 1: In-silico and AI-based Lipid Composition Prediction (continued)
• Growth Opportunity 2: Formulation of Stable LNPs with Improved Functionality
• Growth Opportunity 2: Formulation of Stable LNPs with Improved Functionality (continued)
• Growth Opportunity 3: Automated and Microfluidics-based LNP Manufacturing Platform
• Growth Opportunity 3: Automated and Microfluidics-based LNP Manufacturing Platform (continued)
• Growth Opportunity 4: Directed Development of LNPs for Tissue-targeted Delivery
• Growth Opportunity 4: Directed Development of LNPs for Tissue-targeted Delivery (continued)

Appendix

• Technology Readiness Levels (TRL): Explanation

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