Lipid Nanoparticles Carrying Gemcitabine and Hyaluronidase for Simultaneous Targeting Of Stroma and Pancreatic Cancer Cells: To Overcome Drug Resistance and Improve Permeability: A Review
نویسندگان
1 Navoi State Mining and Technological University, Navoi , Uzbekistan
2 Samarkand State Medical University, Samarkand, Uzbekistan
3 Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
4 Tashkent State Technical University named after Islam Karimov, Tashkent, Uzbekistan
5 Urganch State University, Urganch, Uzbekistan
6 Fergana Medical Institute of Public Health, Fergana, Uzbekistan
7 Fergana Medical Institute of Public Health, Fergana, Uzbekistan
8 National University of Uzbekistan named after Mirzo Ulugbek, Tashkent, Uzbekistan
9 National University of Uzbekistan named after Mirzo Ulugbek, Tashkent, Uzbekistan
10 Jizzakh State Pedagogical University, Jizzakh, Uzbekistan
11 Jizzakh State Pedagogical University, Jizzakh, Uzbekistan
12 Tashkent Medical Academy, Tashkent, Uzbekistan
13 Fergana Medical Institute of Public Health, Fergana, Uzbekistan
doi
10.22052/JNS.2025.01.021چکیده
Pancreatic cancer’s aggressive biology—marked by drug-resistant phenotypes and a desmoplastic stroma—has long presented formidable barriers to effective treatment. Gemcitabine, a cornerstone chemotherapy for this malignancy, faces clinical limitations due to poor tissue penetration and diminished therapeutic efficacy in the face of these physiological hurdles. Hyaluronidase, an enzyme that disrupts the stromal matrix to enhance drug delivery, offers a partial solution but is constrained by suboptimal targeting and risks of nonspecific tissue effects. Emerging as a transformative approach, multifunctional lipid nanoparticles (LNPs) co-encapsulating gemcitabine and hyaluronidase now promise to address these dual challenges synergistically. Engineered with pH-responsive properties, these “smart” LNPs exploit the acidic tumor microenvironment to achieve spatiotemporally controlled release, enhancing stromal degradation while maximizing intracellular gemcitabine delivery. Preclinical studies leveraging Patient-Derived Xenograft (PDX) models have shown remarkable tumor growth suppression, underscoring the potential of this combinatorial platform. Nevertheless, key challenges persist, including optimizing nanoparticle stability in protease-rich environments, refining hyaluronidase dosing to balance stromal modulation with off-target toxicity, and ensuring scalable manufacturing. This review critically examines recent breakthroughs in stimuli-responsive LNP design, evaluates translational gaps through the lens of clinical applicability, and proposes forward-looking strategies to advance this paradigm toward personalized, stroma-targeted therapy for pancreatic cancer.
