Drug-Loaded Red Blood Cell–Derived Carriers for Targeted Delivery to Accelerate Tissue Regeneration

Kulzhan Berikkhanova, Yernur Zakirov, Askhat Zhilkaidarov, Nurgul Daniyeva, Erlan Taigulov, Saken Kozhakhmetov, Ardak Omarbekov, Beibarys E Amankeldin, Gulyash Tanysheva, Nurzhan Berikkhanov

4 more authors

Yessenkhan Sultan, Zhanas Baimagambet, Isah Inuwa, Saule Aliyeva

2026

Full text Open access: Gold Metadata (CSL-JSON)
DOI 10.3390/pharmaceutics18091131
Data confidence 70 medium
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Abstract

Background/Objectives: Diabetic foot ulcers are characterized by persistent inflammation, impaired angiogenesis, and delayed tissue regeneration. Epidermal growth factor (EGF) is an important regulator of wound repair; however, its therapeutic application may be limited by rapid degradation and poor retention within the wound environment. This study investigated the therapeutic efficacy of local administration of EGF and ceftriaxone using autologous red blood cell-derived carriers (RBCDCs) in an experimental model of diabetic wound healing in rats. Methods: Experiments were conducted on 30 albino Wistar rats (250 ± 20 g) with experimentally induced diabetic wounds. In the RBCDC treatment groups, separately prepared drug-loaded RBCDC formulations containing EGF or ceftriaxone were locally administered into the wound. The corresponding comparison groups received the same active agents in free form according to an identical treatment schedule, while an additional control group received topical Levomekol. Results: RBCDC-mediated administration of EGF and ceftriaxone significantly accelerated wound closure and was associated with earlier resolution of inflammation, granulation tissue maturation, re-epithelialization, collagen deposition, and angiogenesis compared with the corresponding free-drug formulations. On day 9, tissue EGF concentration was higher in the RBCDC (EGF + Ctx) group than in the corresponding free-drug group. Additional formulation characterization demonstrated ceftriaxone encapsulation and in vitro release from RBCDCs, as well as in vitro EGF release from EGF-loaded RBCDCs. Conclusions: Autologous RBCDCs represent a promising local drug-carrier platform for the administration of regenerative and antimicrobial agents in experimental diabetic wounds. Further studies are required to establish local pharmacokinetics, systemic exposure, carrier stability, and the mechanisms responsible for the observed therapeutic effects.