Selected Achievements
1. Influence of "drug-material-water" intermolecular interactions on the structure and behavior of formulations:
As a thermodynamically unstable system, the physical stability of amorphous drug-polymer solid dispersion (ASD) is one of the main risks of this formulation. We propose a working roadmap for designing ASDs to reduce the stability risk of ASDs. This idea is widely recognized by industry peers. In addition, we propose that the intermolecular interactions of drug-material-water are the central influencing factors in determining the pharmaceutical performance of ASDs, and we have established a methodology to characterize the drug-material-water interactions. We have also clearly demonstrated the effect of drug-material interactions on the dissolution and bioavailability of drug formulations through in vivo and ex vivo experiments. These works are of great significance for the design and optimization of difficult-to-dissolve drug formulations.
2. Drug delivery strategies for targeting cancer cells with KRAS mutations:
KRAS mutations are considered difficult for targeted drug design. We propose a drug delivery strategy for targeting KRAS mutant cancer cells. This strategy is proposed based on the biological characteristics of KRAS mutant cancer cells that differ from KRAS wild-type normal cells, i.e., enhanced macropinocytosis and low expression of FcRn. Within the field of drug delivery, it is a novel attempt to utilize disease biology mechanisms to target drug delivery to specific genotype cells.
3. Aggregation kinetics and solution stabilization mechanisms for highly concentrated proteins:
Subcutaneous and local injections of protein drugs often require very highly concentrated protein solution formulations. At high concentrations, protein molecular interactions become more complex, which can negatively affect both structural and colloidal stability of proteins and accelerate irreversible protein aggregation, leading to decreased efficacy, decreased apparent product quality, and decreased safety of the medication due to allergic reactions in patients. The design and risk evaluation of highly concentrated protein solutions is generally done in a trial-and-error manner. We try to investigate the key factors and kinetic processes affecting the phase separation and aggregation of protein solutions at the level of physicochemical and colloidal sciences to provide a theoretical basis for the design of highly concentrated protein formulations.
Publications (corresponding/first author papers only)
Wang K, Sun M, Liu S, Wang R, Liu H, Qian F.* Albumin-conjugated flumethasone for targeting and normalization of pancreatic stellate cells. J Control Release. Published online February 22, 2025. doi:10.1016/j.jconrel.2025.02.046
Chen, Z., Wang, M., Duan, W., Xia, Y., Liu, H., & Qian, F.* (2025). Modulating the complement system through epitope-specific inhibition by complement C3 inhibitors. Journal of Biological Chemistry, 108250.
Meng, J.; Chan, M. Y.; Peng, C.; Jiang, X. L.; Qian, F.*, Enhancing leuprolide penetration through enterocytes via the ER-Golgi pathway using lipophilic complexation. European Journal of Pharmaceutics and Biopharmaceutics 2025, 207.
Tian Z, Jiang X, Chen Z, Huang C, Qian F*. Quantifying Protein Shape to Elucidate its influence on Solution Viscosity in High-Concentration Electrolyte Solutions. Mol. Pharmaceutics 2024.
Huang C, Wang Y, Huang J, Liu H, Chen Z, Jiang Y, Chen Y, Qian F*. A bioengineered anti-VEGF protein with high affinity and high concentration for intravitreal treatment of wet age-related macular degeneration. Bioeng Transl Med. 2023;e10632. doi:10.1002/btm2.10632
Zhu, S., Fan, S., Tang, T., Huang, J., Zhou, H., Huang, C., ... & Qian, F*. (2023). Polymorphic nanobody crystals as long‐acting intravitreal therapy for wet age‐related macular degeneration. Bioengineering & Translational Medicine, e10523.
Dou L, Liu H, Wang K, Liu J, Liu lei, Ye J , Wang R, Deng H, Qian F.*; Albumin binding revitalizes NQO1 bioactivatable drugs as novel therapeutics for pancreatic cancer, Journal of Controlled Release, Volume 349, September 2022, Pages 876-889.
Liu L, Chen L, Wouter M, Peter S, Qian F.*; Water-Resistant Drug–Polymer Interaction Contributes to the Formation of Nano-Species during the Dissolution of Felodipine Amorphous Solid Dispersions, Mol. Pharmaceutics. June 27, 2022, https://doi.org/10.1021/acs.molpharmaceut.2c00250
Kong W, Liu Z, Sun M, Liu H, Kong C, Ma J, Wang R, Qian F.*; Synergistic Autophagy Blockade and VDR Signaling Activation Enhance Stellate Cell Reprogramming in Pancreatic Ductal Adenocarcinoma, Cancer Letters. 2022 Jul 28;539:215718. doi: 10.1016/j.canlet.2022.215718. Epub 2022 May 5.
Huang C, Chen C, Franzen L, Anderski J, Qian F *; Spray-Dried Monoclonal Antibody Suspension for High-Concentration and Low-Viscosity Subcutaneous Injection, Mol. Pharmaceutics. April 13, 2022, https://doi.org/10.1021/acs.molpharmaceut.2c00039
Huiqin Liu, Qian F.*, Exploiting macropinocytosis for drug delivery into KRAS mutant cancer. Theranostics. 2022; 12(3): 1321-1332. doi: 10.7150/thno.67889
Fang Yuan, Mengnan Sun, Zhengsheng Liu, Huiqin Liu, Weijian Kong, Rui Wang, Qian F.*, Macropinocytic dextran facilitates KRAS-targeted delivery while reducing drug-induced tumor immunity depletion in pancreatic cancer. Theranostics. 2022; 12(3): 1061-1073. doi: 10.7150/thno.65299
Liu C; Wang C; Wang S; Liu L; Sun C; Qian F*, An Elusive Drug–Drug Cocrystal Prepared Using a Heteroseeding Strategy, Cryst. Growth Des. 2021, 21, 10, 5659–5668, https://doi.org/10.1021/acs.cgd.1c00512
Liu H; Yu S; Qian F*, Opportunities and delusions regarding drug delivery targeting pancreatic cancer-associated fibroblasts, Advanced Drug Delivery Reviews, 2021 May;172:37-51. https://doi.org/10.1016/j.addr.2021.02.012
Mi W; Chen H; Zhu A, Zhang T, Qian F*, Melting point prediction of organic molecules by deciphering the chemical structure into a natural language, Chemical Communications, 2021, 57, 2633 – 2636
Zhou T,; Qian F.*; Adenosine Triphosphate-Induced Rapid Liquid–Liquid Phase Separation of a Model IgG1 mAb, Mol. Pharmaceutics. 2021 18 (1), 267-274， DOI: 10.1021/acs.molpharmaceut.0c00905
Zhou T; Xu L; Zhang N;, Qian F*,First-order nucleation and subsequent growth promote liquid-liquid phase separation of a model IgG1 mAb, Int. J. Pharm., 588 (2020) 119681
Wang S,; Liu C,; Chen H.; Zhu A.; Qian F*, Impact of Surfactants on Polymer Maintained Nifedipine Supersaturation in Aqueous Solution, Pharmaceutical Research, volume 37, Article number: 113 (2020)
Yuan F; Sun M; Liu H; Qian F.*, Albumin-conjugated drug is irresistible by single gene mutation of endocytic system: verification by genome-wide CRISPR-Cas9 loss-of function screens, Journal of Controlled Release,Vol 323, 10 July 2020, Pages 311-320
Hu C.; Liu Z.; Liu C.; Zhang Y.; Fan H.; Qian F.*; Improvement of Antialveolar Echinococcosis Efficacy of Albendazole by a Novel Nanocrystalline Formulation with Enhanced Oral Bioavailability, ACS Infect. Dis. 2020, 6, 5, 802–810
Hu C.; Liu Z.; Liu C.; Li J.; Xu L.; Chen C.; Fan H.; Qian F.*; I Enhanced Oral Bioavailability and Anti-Echinococcosis Efficacy of Albendazole Achieved by Optimizing the “Spring” and “Parachute”, Mol. Pharmaceutics. 2019, 16, 12, 4978–4986
Liu Z.; Zhang L.; Tian Z.; Kong C.; Liu C.; Liu H.; Yuan F.; Kong W.; Qian F.*; Paclitaxel and Itraconazole Co-encapsulated Micelle Prolongs the Survival of Spontaneous LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre Genetically Engineered Mouse Model of Pancreatic Cancer, Advanced Therapeutics. 2019, 1900032, DOI: 10.1002/adtp.201900032
Chen Y.; Chen H.; Wang S.; Liu C.; Qian F*.; A Single Hydrogen to Fluorine Substitution Reverses the Trend of Surface Composition Enrichment of Sorafenib Amorphous Solid Dispersion upon Moisture Exposure, Pharmaceutical Research, (2019) 36: 105. https://doi.org/10.1007/s11095-019-2632-5
Kong C; Li Y; Liu Z; Ye J; Wang Z; Zhang L; Kong W.; Liu H.; Liu C.; Pang H.; Hu Z.; Gao J.; and Qian F*, Targeting the Oncogene KRAS Mutant Pancreatic Cancer by Synergistic Blocking of Lysosomal Acidification and Rapid Drug Release, ACS Nano, 2019 Apr 23;13(4):4049-4063. doi: 10.1021/acsnano.8b08246.
Chen H.; Zhang X.; Cheng Y.; Qian F*, Preparation of smectic itraconazole nanoparticles with tunable periodic order using microfluidics based anti-solvent precipitation, CrystEngComm, 2019, 21, 2362
Liu H; Sun M; Liu Z; Kong C; Kong W; Ye J; Gong J; Huang D; Qian F.*, KRAS-enhanced macropinocytosis and reduced FcRn-mediated recycling sensitize pancreatic cancer to albumin-conjugated drugs, Journal of Controlled Release, Vol 296, 28 February 2019, Pages 40-53
Liu C; Xu C; Yu J; Pui Y; Chen H; Wang S; Zhu A; Li J; Qian F.*, Impact of a Single Hydrogen Substitution by Fluorine on the Molecular Interaction and Miscibility between Sorafenib and Polymers, Mol. Pharmaceutics, 2019, 16 (1), pp 318–326
Chen, Y.; Pui, Y.; Chen, H.; Wang, S; Serno, P.; Tonnis, W.; Chen, L.; Qian F.*, Polymer mediated drug supersaturation controlled by drug-polymer interactions persisting in aqueous environment, 19 Nov 2018, Mol. Pharmaceutics, 2019, 16 (1), pp 205–213
Zhang L, Liu Z, Kong C, Liu C, Yang K, Chen H, Huang J, Qian F*., Improving Drug Delivery of Micellar Paclitaxel against Non‐Small Cell Lung Cancer by Coloading Itraconazole as a Micelle Stabilizer and a Tumor Vascular Manipulator, Small, 16 November 2018 https://doi.org/10.1002/smll.201802112
Liu L.; Kong C.; Huo M.; Liu C.; Peng L.; Zhao T.; Wei Y.; Qian F.* Yuan J.*; Schiff base interaction tuned mesoporous organosilica nanoplatforms with pH-responsive degradability for efficient anti-cancer drug delivery in vivo, Chemical Communications, 2018, 54, 9190-9193
Wang S,; Liu C,; Chen Y.; Zhu A.;Qian F* Aggregation of Hydroxypropyl Methylcellulose Acetate Succinate under Its Dissolving pH and the Impact on Drug Supersaturation, Mol. Pharmaceutics, 2018, 15, 4643−4653
Pui Y.; Chen Y.; Chen H.; Wang S.; Liu C.; Tonnis W.; Chen L.; Serno P.; Bracht S.; Qian F.*, Maintaining Supersaturation of Nimodipine by PVP with or without the Presence of Sodium Lauryl Sulfate and Sodium Taurocholate, Mol. Pharmaceutics, 2018, 15 (7), pp 2754–2763
Chen Z., Yang K., Huang C., Zhu A., Yu L., Qian F.* Surface Enrichment and Depletion of the Active Ingredient in Spray Dried Amorphous Solid Dispersions, Pharmaceutical Research (2018) Jan 29;35(2):38.
Wang S.; Liu C.; Chen Y.; Zhang Z.; Zhub A.;Qian F.*; A high-sensitivity HPLC-ELSD method for HPMC-AS quantification and its application in elucidating the release mechanism of HPMC-AS based amorphous solid dispersions, Euro. J. Pharm. Sci. Vol. 122, 15 September 2018, Pages 303-310
Chen H, Pui Y, Liu C, Chen Z, Su C, Hageman M, Hussain M, Haskell R, Stefanski K, Foster K, Gudmundsson O, Qian, F*, Moisture-Induced Amorphous Phase Separation of Amorphous Solid Dispersions: Molecular Mechanism, Microstructure, and Its Impact on Dissolution Performance, J Pharm Sci., January 2018, Volume 107, Issue 1, Pages 317–326
Liu C.; Liu Z.; Chen Y.; Chen Z.; Chen H.; Pui Y.; Qian F.*, Oral bioavailability enhancement of β-lapachone, a poorly soluble fast crystallizer, by cocrystal, amorphous solid dispersion, and crystalline solid dispersion, Euro. J. Pharm. Biopharm, Vol. 124, March 2018, Pages 73-81, https://doi.org/10.1016/j.ejpb.2017.12.016
Zhang X., Chen H., Qian F.*; Cheng Y., Preparation of itraconazole nanoparticles by anti-solvent precipitation method using a cascaded microfluidic device and an ultrasonic spray drier, Chemical Engineering Journal, 334 (2018) 2264-2272
Zhang L, Liu Z, Yang K, Kong C, Liu C, Chen H, Huang J,Qian F*. Tumor Progression of Non-Small Cell Lung Cancer Controlled by Albumin and Micellar Nanoparticles of Itraconazole, a Multitarget Angiogenesis Inhibitor, Mol Pharmaceutics. 2017, 14 (12), pp 4705–4713
Zhang L, Sun H, Chen Z, Liu Z, Huang N, Qian F.*; Intermolecular Interactions between Coencapsulated Drugs Inhibit Drug Crystallization and Enhance Colloidal Stability of Polymeric Micelles. Mol Pharmaceutics. 2017, 14, 3568−3576
Wang S, Zhang X, Wu G, Tian Z, Qian F.*; Optimization of high-concentration endostatin formulation: Harmonization of excipients' contributions on colloidal and conformational stabilities., Int J Pharm. 2017 Sep 15;530(1-2):173-186. doi: 10.1016/j.ijpharm.2017.07.057. Epub 2017 Jul 26.
Wu G, Wang Co-First S, Tian Z, Zhang N, Sheng H, Dai W, Qian F.*, Elucidating the Weak Protein-Protein Interaction Mechanisms behind the Liquid-Liquid Phase Separation of a mAb Solution by Different Types of Additives. Eur J Pharm Biopharm. Vol. 120, November 2017, Pages 1-8.
Wang, S.; Wu, G.; Zhang, X.; Tian, Z.; Zhang, N.; Hu, T.; Dai.; W.; Qian F*, Stabilizing two IgG1 monoclonal antibodies by surfactants: Balance between aggregation prevention and structure perturbation, Euro. J. Pharm. Biopharm., Volume 114, May 2017, Pages 263–277
Chen, Z.; Liu, CY.; Zhang, L.; Qian F.*; Dissolution Characteristics of Fast-Crystallizing β-Lapachone within Different Semicrystalline Microstructures of Polyethylene Glycol or Poly(ethylene oxide)–Poly(propylene oxide)–Poly(ethylene oxide) Triblock Copolymer, Cryst. Growth Des., 2016, 16, 5367-5376
Chen YJ.; Wang S; Wang S.; Liu C.; Su, C.; Hageman, M.; Hussain, M.; Haskell. R.; Stefanski K.; Qian F*.; Sodium Lauryl Sulfate Competitively Interacts with HPMC-AS and Consequently Reduces Oral Bioavailability of Posaconazole/HPMC-AS Amorphous Solid Dispersion, Mol. Pharmaceutics, 2016, 13, 2787-2795
Chen YJ.; Wang S; Wang S.; Liu C.; Su, C.; Hageman, M.; Hussain, M.; Haskell. R.; Stefanski K.; Qian F*.; Initial Drug Dissolution from Amorphous Solid Dispersions Controlled by Polymer Dissolution and Drug-Polymer Interaction, Pharmaceutical Research, 2016, 33(10), 2445-2458.
Liu C, Chen Z, ChenYJ.; Lu J’; Li Y.; Wang S.; Wu G.; Qian F* Improving Oral Bioavailability of Sorafenib by Optimizing the “Spring” and “Parachute” Based on Molecular Interaction Mechanisms, Mol. Pharmaceutic,2016, 13 (2), pp 599–608
Wang S, Zhang N, Hu T, Dai W, Feng X, Zhang X, and Qian F*.; Viscosity-Lowering Effect of Amino Acids and Salts on Highly Concentrated Solutions of Two IgG1 Monoclonal Antibodies, Mol. Pharmaceutics, 2015, 12 (12), pp 4478–4487
Zhang L, Zhen Chen, Kuan Yang, Chun Liu, Jinming Gao, and Qian F*.; β-Lapachone and Paclitaxel Combination Micelles with Improved Drug Encapsulation and Therapeutic Synergy as Novel Nanotherapeutics for NQO1-Targeted Cancer Therapy, Mol.Pharmaceutics, 2015, 12 (11), pp 3999–4010
Liu C, Kong C, Wu G, Zhu J, Javid B, Qian F*, Uniform and amorphous rifampicin microspheres obtained by freezing induced LLPS during lyophilization, Int. J. Pharm., Volume 495, Issue 1, 10 November 2015, Pages 500–507
Wang S, Liu H, Zhang X, Qian F*, Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies, Protein & Cell, July 2015, Volume 6, Issue 7, pp 480-503
Chen, Z.; Liu,ZS.; Qian F.*; Crystallization of Bifonazole and Acetaminophen within the Matrix of Semicrystalline, PEO-PPO-PEO Triblock Copolymers, Mol. Pharmaceutics, 2015 Feb 21;12(2):590-9.
Chen YJ.; Liu CY.; Chen.Z.; Su, C.; Hageman, M.; Hussain, M.; Haskell. R.; Stefanski K.; Qian F*.; Drug-polymer-water Interaction and its Implication to the Dissolution Performance of Amorphous Solid Dispersions, Mol. Pharmaceutics, 2015 Feb 12;12(2):576-89.
Qian F.*; Wang, J.; Hartley, R.; Tao, J.; Haddadin, R.; Mathias, N..; Hussain, M. Solution Behavior of PVP-VA and HPMC-AS Based Amorphous Solid Dispersions and Their Bioavailability Implications, Pharmaceutical Research, 2012, Oct 29 (10) 2765-76
Qian F.*; Huang, J.; Zhu, Q.; Haddadin, R.; Gawel, J.; Garmise, R.; Hussain, M. Is a Distinctive Single Tg a Reliable Indicator for the Homogeneity of Amorphous Solid Dispersion? International Journal of Pharmaceutics, Volume 395, Issues 1-2, 16 August 2010, Pages 232-235
Qian F.*; Huang, J.; Hussain, M. Drug-polymer solubility and miscibility: stability consideration and practical challenges in amorphous solid dispersion development. Journal of Pharmaceutical Sciences, 2010, 99 (7), 2941-2947
Qian F.*; Ni, N.; Burton, L.; Wang, F.; Desikan, S.; Hussain, M.; Smith, RL. Sustained Release Subcutaneous Delivery of BMS-686117, a GLP-1 Receptor Agonist, Via Zinc Adduct. International Journal of Pharmaceutics, Vol. 374, Issues 1-2, 5 June 2009, 46-52
Qian, F.*; Moench, P.; Mathias, N.; Desikan, S.; Hussain, M.; Smith, RL. Pulmonary Delivery of a GLP-1 Receptor Agonist, BMS-686117. International Journal of Pharmaceutics, Vol. 366, 2009, 218–220
Qian F.*; Ni, N.; Chen, JW.; Desikan, S.; Naringrekar, V.; Hussain, M.; Smith, RL. Formation of Zinc Peptide Spherical Microparticles during Lyophilization From tert-Butyl Alcohol/Water Co-solvent System. Pharmaceutical Research, Vol. 25, No. 12, December 2008
Qian F.*; Tao, J..; Desikan, S.; Hussain, M.; Smith, RL. Mechanistic Investigation of Pluronic® Based Nano-crystalline Solid Dispersion. Pharmaceutical Research, 2007, 24(8):1551-60.