Singh Dilpreet
Department of Pharmaceutics, School of Pharmaceutical Sciences, CT University, Ferozepur Rd, Sidhwan Khurd, Ludhiana, Punjab, 142024, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 19. doi: 10.1007/s00210-025-04449-5.
The delivery of biologic drugs presents unique formulation challenges due to their high molecular weight, instability in physiological environments, and complex pharmacokinetics. Hybrid excipient systems, particularly those combining hydroxypropyl methylcellulose (HPMC) and polyethylene glycol (PEG), offer a versatile platform for addressing these issues. Hydroxypropyl methylcellulose (HPMC), a semi-synthetic polymer, is widely recognized for its gel-forming ability, biocompatibility, and capacity to enable sustained drug release. Polyethylene glycol (PEG), a hydrophilic polyether, is commonly employed to enhance solubility, reduce protein aggregation, and improve mucosal permeability. This review presents a focused analysis of HPMC-PEG-based different formulation strategies that support controlled, sustained, and site-specific delivery of biologics across various routes including oral, nasal, ocular, parenteral, and pulmonary. Furthermore, the review discusses mechanistic insights, PEG-related immunogenicity concerns, and regulatory considerations that are critical for clinical translation. Key aspects such as formulation strategies, physicochemical properties, in vitro and in vivo performance, and targeting capabilities are discussed. Additionally, the challenges associated with the scale-up, regulatory approval, and potential toxicity of these hybrid systems are explored. By integrating physicochemical behavior with route-specific delivery outcomes, this review provides a consolidated, application-oriented perspective that bridges formulation science with therapeutic advancement in biologics. This distinguishes it from prior work and offers practical guidance for excipient scientists and pharmaceutical developers. This review also provides insights into the future directions and applications of HPMC-PEG hybrid excipients and the developed nanoformulations in personalized medicine and sustained-release drug product.
生物药物的递送由于其高分子量、在生理环境中的不稳定性以及复杂的药代动力学而带来了独特的制剂挑战。混合辅料系统，特别是那些将羟丙基甲基纤维素（HPMC）和聚乙二醇（PEG）结合的系统，为解决这些问题提供了一个通用平台。羟丙基甲基纤维素（HPMC）是一种半合成聚合物，因其凝胶形成能力、生物相容性以及实现药物持续释放的能力而被广泛认可。聚乙二醇（PEG）是一种亲水性聚醚，通常用于提高溶解度、减少蛋白质聚集以及改善粘膜通透性。本综述重点分析了基于HPMC-PEG的不同制剂策略，这些策略支持生物药物通过口服、鼻腔、眼部、肠胃外和肺部等各种途径进行可控、持续和位点特异性递送。此外，该综述还讨论了对临床转化至关重要的作用机制见解、与PEG相关的免疫原性问题以及监管考量。讨论了制剂策略、物理化学性质、体外和体内性能以及靶向能力等关键方面。此外，还探讨了这些混合系统在放大生产、监管批准以及潜在毒性方面的挑战。通过将物理化学行为与特定途径的递送结果相结合，本综述提供了一个综合的、以应用为导向的视角，将制剂科学与生物药物的治疗进展联系起来。这使其有别于先前的工作，并为辅料科学家和药物开发者提供了实用指导。本综述还深入探讨了HPMC-PEG混合辅料以及所开发的纳米制剂在个性化医疗和缓释药物产品中的未来方向和应用。
