THE ROLE OF THE DISEASE-SPECIFIC MICROENVIRONMENT IN THE DESIGN OF BIODEGRADABLE POLYMERIC DRUG DELIVERY SYSTEMS
Dinya Mariann
Gyógyszertudományok és Egészségügyi Technológiák Tagozat
Dr. Zelkó Romána
SE Semmelweis Szalon
2026-09-04 17:00:00
Modern Trends in Pharmaceutical Scientific Research
Dr. Antal István
Dr. Antal István és Dr. Mórocz Gábor
Dr. Lengyel Miléna
Dr. Molnár László
Dr. Szökő Éva
Dr. Papp Renáta
Dr. Erdélyi Lóránd
The performance of drug delivery systems based on biodegradable polymers is determined not only by material properties and pharmaceutical design. It also depends on how the carrier behaves in the pathological microenvironment where drug release, local retention and therapeutic action must take place. The aim of this dissertation was to examine whether polymer selection can be viewed as a decision tailored to the target disease, and whether recurring relationships can be identified among local pathobiochemical factors, responsive polymer structures and successful carrier systems.
The work was grounded in our previous experimental, human and animal findings. Studies of Eudragit L 100-55 and sodium alginate matrices showed that the pH and ionic composition of the surrounding medium markedly influence swelling, volume change and drug release. In porphyria cutanea tarda, analysis of 19 macro and trace elements in whole blood indicated a reorganization of the internal chemical environment associated with the disease. In rabbits receiving a cholesterol enriched diet, modification of myeloperoxidase activity was accompanied by morphological changes in the aortic wall, supporting an active role of the oxidative and inflammatory microenvironment in tissue organization.
The central part of the dissertation was a structured analysis of recent preclinical literature on biodegradable polymer carriers that respond to local stimuli. PubMed and Scopus were searched for original articles published from 1 January 2020 to 31 August 2025, and the process was reported in accordance with PRISMA 2020. The final analysis included 65 in vivo studies. Disease model, polymer family, carrier type, dominant trigger, route of administration and direction of the therapeutic outcome were recorded in a common framework. Associations among polymer composition, response mechanism and disease group were assessed using cross tabulation, chi square tests, Cramér's V, standardized residuals and direction of effect synthesis.
The successful systems were not distributed randomly. In inflammatory bowel disease, polysaccharide and methacrylate systems responsive to pH, ionic conditions and microbial activity occurred most often. Joint and cartilage disorders were characterized by biomimetic matrices sensitive to enzymes, particularly those based on hyaluronic acid and collagen. In cardiovascular and other models characterized by oxidative inflammation, platforms responsive to reactive oxygen species, sometimes combined with sensitivity to shear stress, were prominent. In the heterogeneous tumor microenvironment, composite and hybrid systems capable of responding to several stimuli were particularly prominent.
The main conclusion is that polymer performance cannot be regarded as a universal property independent of indication. Rational material selection requires a match between the chemical responsiveness of the polymer and the dominant microenvironmental features of the target disease. Biocompatibility, biodegradability, manufacturability, stability and safety remain essential, but pathophysiological fit provides an additional organizing principle for formulation. This approach may support the development of drug carrier systems that are more precisely targeted, better calibrated to disease and designed with a clearer therapeutic rationale.
