Jain Sanyog, Mali Shivani, Akhtar Junia, Dora Chander Parkash, Mahajan Rahul R
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, Punjab, 160062, India.
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.
AAPS PharmSciTech. 2025 Jun 27;26(6):172. doi: 10.1208/s12249-025-03168-7.
Topical drug delivery systems offer a targeted and patient-compliant approach for managing psoriasis, enabling noninvasive, localized, and sustained therapy, with reduced systemic side effects and improved therapeutic outcomes. In this study, we prepared phospholipid complex (PLC) based gel of methotrexate (MTX) and erlotinib (ERL) as a potential dual treatment for psoriasis. The phospholipids used in this study were biocompatible and exhibited enhanced skin permeation. The physical interactions between drugs and phospholipids in the MTX-loaded phospholipid complex (MPLC) and ERL-loaded phospholipid complex (EPLC) were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (H NMR), and powder X-ray diffraction (P-XRD). Scanning electron microscopy (SEM) confirmed amorphization of the drug upon complexation, and transmission electron microscopy (TEM) indicated that the complexes formed a spherical morphology. Furthermore, gel-embedded drug-phospholipid complexes exhibited slower diffusion-based sustained release profiles, with ~ 40% release of ERL from EPLC and ~ 60% release of MTX from MPLC over 24 h, in contrast to the faster release of ~ 65% and ~ 90% observed for free ERL and MTX, respectively. Skin permeation studies (Franz diffusion cells), dermal pharmacokinetics studies, and in vivo antipsoriatic activity studies (imiquimod (IMQ)-induced psoriasis model) were performed to evaluate the efficacy of the optimized formulation. This first-in-class combination therapy provides better lesion control and reduced inflammation while minimizing systemic adverse effects, highlighting the potential of drug-phospholipid complexes for targeted, sustained delivery in psoriasis treatment.
局部给药系统为银屑病的治疗提供了一种靶向且患者依从性良好的方法，能够实现无创、局部和持续治疗，减少全身副作用并改善治疗效果。在本研究中，我们制备了基于磷脂复合物（PLC）的甲氨蝶呤（MTX）和厄洛替尼（ERL）凝胶，作为银屑病的潜在双重治疗方案。本研究中使用的磷脂具有生物相容性，并表现出增强的皮肤渗透性。通过差示扫描量热法（DSC）、傅里叶变换红外光谱（FT-IR）、核磁共振光谱（H NMR）和粉末X射线衍射（P-XRD）对负载MTX的磷脂复合物（MPLC）和负载ERL的磷脂复合物（EPLC）中药物与磷脂之间的物理相互作用进行了表征。扫描电子显微镜（SEM）证实了药物在络合后形成无定形，透射电子显微镜（TEM）表明复合物形成了球形形态。此外，凝胶包埋的药物 - 磷脂复合物表现出基于扩散的较慢持续释放曲线，在24小时内，ERL从EPLC中的释放率约为40%，MTX从MPLC中的释放率约为60%，相比之下，游离ERL和MTX的释放率分别为约65%和约90%，释放速度更快。进行了皮肤渗透研究（Franz扩散池）、皮肤药代动力学研究和体内抗银屑病活性研究（咪喹莫特（IMQ）诱导的银屑病模型）以评估优化制剂的疗效。这种一流的联合疗法在将全身不良反应降至最低的同时，提供了更好的皮损控制和炎症减轻效果，突出了药物 - 磷脂复合物在银屑病治疗中靶向、持续递送的潜力。
