用於製藥行業的脂質納米顆粒：臨床前和臨床進展

本報告重點介紹了 LNP 開發在臨床前和臨床階段的主要研發進展，用於治療各種疾病，包括癌症、心血管和神經退行性疾□□病。它對當前的研究和進展進行了深入分析顆粒使用的工業發展。我們還提供了有關使用 LNP 作為疫苗遞送 mRNA 載體的工業介紹和未來前景的見解。它還提供了有關 LNP 生產和利用方面的挑戰和驅動因素、關鍵政策、創新和主要市場進入者的信息。

內容

戰略要務

• 為什麼越來越難成長？
• 戰略要務 8 (TM)
• 三大戰略要務對製藥行業脂質納米顆粒研發進步的影響
• 增長機會推動增長 Pipeline Engine(TM)
• 調查方法

增長機會分析

• 脂質納米顆粒：概述和意義
• LNP 比脂質體更適合用於核酸遞送
• 下一代脂質納米載體顯示出可用於封裝和大規模生產的有前途的特性
• 第二代 LNP 提供更大的設計靈活性和更高的穩定性
• 第一代脂質納米粒子廣泛應用於化妝品、食品和飲料以及保健品行業
• 調查範圍
• 細分
• 增長動力
• 抑制增長的因素

LNP：配方、製造和治療給藥

• LNP 是脂質和穩定劑的混合物
• 獲批的 LNP 配方可封裝具有不同化學和物理特性的多種貨物
• 脂質和水相的混合比決定了 LNP 的大小及其捕獲效率
• 高壓均質化是 LNP 大規模生產的合適選擇
• 微流體和超臨界流體技術改進了顆粒大小和分佈控制
• 配方技術在確定尺寸、溶劑殘留和分佈方面起著重要作用
• LNP 的主動和被動靶向顯示治療藥物的細胞滲透得到改善，全身毒性最小
• 合理設計脂質以提高 mRNA 疫苗和治療劑的體內穩定性，促進商業化
• 基於脂質的納米載體越來越多地用於治療各種疾病

LNP：新興的研發領域

• 與抗體/配體偶聯的 LNP 顯示出靶向癌症的高度特異性
• 新型磷脂組合、接頭和膽固醇替代物的設計和使用提高了 LNP 的體內穩定性、安全性和轉染
• 脂質和聚合物的混合 LNP 具有增強的穩定性和靶向性，從而產生協同效應
• 在線檢測和跟蹤 LNP 配方可最大限度地縮短生產時間並實現過程的反饋控制
• 肌肉內和靜脈內給藥途徑是基於 LNP 療法的首選
• LNP 表面修飾以及脂質和貨物的凍乾提高了長期儲存穩定性

藥物和疫苗的臨床情況、財務和創新觀點

• 北美獲得大量資金用於 LNP 療法的商業開發
• 私人資金側重於改進用於疫苗和免疫療法的 LNP 配方
• 參與熱穩定性和靶向 LNP 療法的臨床試驗
• 製藥公司在 LNP 穩定性、生物降解性、配方和成本效益方面進行創新
• 脂質製造商與 API 開發商合作，利用基於 LNP 的療法
• 使用 LNP 的治療和疫苗製劑正處於臨床試驗的各個階段

知識產權分析

• 北美在 LNP 專利申請中所佔份額最高
• 主要的 LNP 和 mRNA 公司就專利侵權問題展開鬥爭

增長機會領域

• 增長機會 1：基於計算機和 AI 的脂質成分預測
• 增長機會 2：配製具有增強功能的穩定 LNP
• 增長機會 3：基於微流體的自動化 LNP 製造平台
• 增長機會 4：定向開髮用於組織靶向遞送的 LNP

附錄

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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