用于製药行业的脂质纳米颗粒：临床前和临床进展

本报告重点介绍了 LNP 开发在临床前和临床阶段的主要研发进展，用于治疗各种疾病，包括癌症、心血管和神经退行性疾□□病。它对当前的研究和进展进行了深入分析颗粒使用的工业发展。我们还提供了有关使用 LNP 作为疫苗递送 mRNA 载体的工业介绍和未来前景的见解。它还提供了有关 LNP 生产和利用方面的挑战和驱动因素、关键政策、创新和主要市场进入者的信息。

内容

战略要务

• 为什么越来越难成长？
• 战略要务 8 (TM)
• 三大战略要务对製药行业脂质纳米颗粒研发进步的影响
• 增长机会推动增长 Pipeline Engine(TM)
• 调查方法

增长机会分析

• 脂质纳米颗粒：概述和意义
• LNP 比脂质体更适合用于核酸递送
• 下一代脂质纳米载体显示出可用于封装和大规模生产的有前途的特性
• 第二代 LNP 提供更大的设计灵活性和更高的稳定性
• 第一代脂质纳米粒子广泛应用于化妆品、食品和饮料以及保健品行业
• 调查范围
• 细分
• 增长动力
• 抑制增长的因素

LNP：配方、製造和治疗给药

• LNP 是脂质和稳定剂的混合物
• 获批的 LNP 配方可封装具有不同化学和物理特性的多种货物
• 脂质和水相的混合比决定了 LNP 的大小及其捕获效率
• 高压均质化是 LNP 大规模生产的合适选择
• 微流体和超临界流体技术改进了颗粒大小和分布控制
• 配方技术在确定尺寸、溶剂残留和分布方面起着重要作用
• LNP 的主动和被动靶向显示治疗药物的细胞渗透得到改善，全身毒性最小
• 合理设计脂质以提高 mRNA 疫苗和治疗剂的体内稳定性，促进商业化
• 基于脂质的纳米载体越来越多地用于治疗各种疾病

LNP：新兴的研发领域

• 与抗体/配体偶联的 LNP 显示出靶向癌症的高度特异性
• 新型磷脂组合、接头和胆固醇替代物的设计和使用提高了 LNP 的体内稳定性、安全性和转染
• 脂质和聚合物的混合 LNP 具有增强的稳定性和靶向性，从而产生协同效应
• 在线检测和跟踪 LNP 配方可最大限度地缩短生产时间并实现过程的反馈控制
• 肌肉内和静脉内给药途径是基于 LNP 疗法的首选
• LNP 表面修饰以及脂质和货物的冻干提高了长期储存稳定性

药物和疫苗的临床情况、财务和创新观点

• 北美获得大量资金用于 LNP 疗法的商业开发
• 私人资金侧重于改进用于疫苗和免疫疗法的 LNP 配方
• 参与热稳定性和靶向 LNP 疗法的临床试验
• 製药公司在 LNP 稳定性、生物降解性、配方和成本效益方面进行创新
• 脂质製造商与 API 开发商合作，利用基于 LNP 的疗法
• 使用 LNP 的治疗和疫苗製剂正处于临床试验的各个阶段

知识产权分析

• 北美在 LNP 专利申请中所占份额最高
• 主要的 LNP 和 mRNA 公司就专利侵权问题展开斗争

增长机会领域

• 增长机会 1：基于计算机和 AI 的脂质成分预测
• 增长机会 2：配製具有增强功能的稳定 LNP
• 增长机会 3：基于微流体的自动化 LNP 製造平台
• 增长机会 4：定向开髮用于组织靶向递送的 LNP

附录

下一步

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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