Fanny Joubert

Bio: Fanny Joubert is an academic researcher from University College London. The author has contributed to research in topics: Reversible addition−fragmentation chain-transfer polymerization & Polymerization. The author has an hindex of 4, co-authored 5 publications receiving 90 citations.

Stereolithography (SLA) 3D printing of an antihypertensive polyprintlet: Case study of an unexpected photopolymer-drug reaction

Abstract: The introduction of three-dimensional (3D) printing in the pharmaceutical arena has caused a major shift towards the advancement of modern medicines, including drug products with different configurations and complex geometries. Otherwise challenging to create via conventional pharmaceutical techniques, 3D printing technologies have been explored for the fabrication of multi-drug loaded dosage forms to reduce pill burden and improve patient adherence. In this study, stereolithography (SLA), a vat polymerisation technique, was used to manufacture a multi-layer 3D printed oral dosage form (polyprintlet) incorporating four antihypertensive drugs including irbesartan, atenolol, hydrochlorothiazide and amlodipine. Although successful in its fabrication, for the first time, we report an unexpected chemical reaction between a photopolymer and drug. Fourier Transform Infrared (FTIR) spectroscopy and Nuclear Magnetic Resonance (NMR) spectroscopy confirmed the occurrence of a Michael addition reaction between the diacrylate group of the photoreactive monomer and the primary amine group of amlodipine. The study herein demonstrates the importance of careful selection of photocurable resins for the manufacture of drug-loaded oral dosage forms via SLA 3D printing technology.

Development of a Gemcitabine-Polymer Conjugate with Prolonged Cytotoxicity against a Pancreatic Cancer Cell Line

Abstract: Gemcitabine (GEM) is a nucleoside analogue of deoxycytidine with limited therapeutic efficacy due to enzymatic hydrolysis by cytidine deaminase (CDA) resulting in compromised half-life in the bloodstream and poor pharmacokinetics. To overcome these limitations, we have developed a methacrylate-based GEM-monomer conjugate, which was polymerized by reversible addition–fragmentation chain transfer (RAFT) polymerization with high monomer conversion (∼90%) and low dispersity (<1.4). The resulting GEM-polymer conjugates were found to form well-defined sub-90 nm nanoparticles (NPs) in aqueous suspension. Subsequently, the GEM release was studied at different pH (∼7 and ∼5) with and without the presence of an enzyme, Cathepsin B. The GEM release profiles followed a pseudo zero-order rate and the GEM-polymer conjugate NPs were prone to acidic and enzymatic degradation, following a two-step hydrolysis mechanism. Furthermore, the NPs exhibited significant cytotoxicity in vitro against a model pancreatic cell line. A...

Comparison of Thermoresponsive Hydrogels Synthesized by Conventional Free Radical and RAFT Polymerization.

Abstract: We compared the influence of the polymerization mechanism onto the physical characteristics of thermoresponsive hydrogels. The Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels were successfully synthesized using reversible addition-fragmentation chain-transfer (RAFT) and free radical polymerization (FRP). The gels were prepared while using different crosslinker feed and monomer concentration. The swelling, dye release, and hydrolytic stability of the gels were investigated in water, or in representative komostrope and chaotrope salt solutions at room temperature and at 37 °C. It was found that the swelling ratio (SR) of the RAFT gels was significantly higher than that of the FRP gels; however, an increased crosslinking density resulted in a decrease of the SR of the RAFT gels as compared to the corresponding gels that are made by FRP, which indicates the limitation of the cross-linking efficiency that is attained in RAFT polymerization. Additionally, an increased monomer concentration decreased the SR of the RAFT gels, whereas a similar SR was observed for the FRP gels. However, the SR of both RAFT and FRP gels in NaSCN and Na2SO4 solutions were similar. Finally, the rate of dye release was significantly slower from the RAFT gels than the FRP gels and the hydrolytic stability of the RAFT gels was lower than that of FRP gels in water, but maintained similar stability in Na2SO4 and NaSCN solutions.

Hierarchically designed hybrid nanoparticles for combinational photochemotherapy against a pancreatic cancer cell line

Abstract: Here, we report the formulation of hybrid nanoparticles consisting of aggregated gold nanoparticles (GNPs) impregnated into a gemcitabine–polymer conjugate matrix that exhibit synergistic photo-chemo-therapeutic activity against pancreatic cancer Well-defined, sub-100 nm hybrid NPs were successfully formulated and their photothermal conversion efficiency was evaluated, which was found to be as high as 63% in the red-visible spectrum By varying the GNP and GEM–polymer feed, it was possible to control the red-shifting of the surface plasmon resonance at therapeutically relevant wavelengths The hybrid NPs exhibited significant cytotoxicity against MiaPaCa-2 cells with a half-maximal inhibitory concentration (IC50) of 00012 mg mL−1; however the IC50 decreased by a factor of 2 after the cells were irradiated with a continuous wave red laser for 1 min (14 W cm−2) Although the irradiation of the aggregated GNPs loaded in the hybrid NPs produced a higher thermal effect for the same amount of non-loaded GNPs, the IC50 of the hybrid NPs was significantly lower than that of the free GNPs, hence indicating a synergistic effect of the polymer bound GEM and the GNPs

Pancreatic Cancer Chemoresistance to Gemcitabine.

Abstract: Pancreatic ductal adenocarcinoma (PDAC), commonly referred to as pancreatic cancer, ranks among the leading causes of cancer-related deaths in the Western world due to disease presentation at an advanced stage, early metastasis and generally a very limited response to chemotherapy or radiotherapy. Gemcitabine remains a cornerstone of PDAC treatment in all stages of the disease despite suboptimal clinical effects primarily caused by molecular mechanisms limiting its cellular uptake and activation and overall efficacy, as well as the development of chemoresistance within weeks of treatment initiation. To circumvent gemcitabine resistance in PDAC, several novel therapeutic approaches, including chemical modifications of the gemcitabine molecule generating numerous new prodrugs, as well as new entrapment designs of gemcitabine in colloidal systems such as nanoparticles and liposomes, are currently being investigated. Many of these approaches are reported to be more efficient than the parent gemcitabine molecule when tested in cellular systems and in vivo in murine tumor model systems; however, although promising, their translation to clinical use is still in a very early phase. This review discusses gemcitabine metabolism, activation and chemoresistance entities in the gemcitabine cytotoxicity pathway and provides an overview of approaches to override chemoresistance in pancreatic cancer.

Tumor-stromal crosstalk in pancreatic cancer and tissue fibrosis

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with high morbidity and mortality worldwide. To date, limited therapeutic achievements targeting cell proliferation and related mechanisms has led researchers to focus on the microenvironment where pancreatic cancers develop. The anomalous proliferation of stromal cells, such as pancreatic stellate cells, and an increased deposition of altered matrix proteins create an environment that facilitates tumor growth, metastasis and drug resistance. Here, we summarize our understanding of recent advances in research about the role of fibrosis in pancreatic cancer progression, with particular emphasize on the involvement of fibrotic machineries such as wound healing, extra cellular matrix degradation, and epithelial-to-mesenchymal transition. The precise influence of these mechanisms on the biological behaviors and growth of cancer cells has great impact on clinical therapy and therefore deserves more attention. We also discuss the role of various stromal components in conferring drug resistance to PDAC which further worsening the pessimistic disease prognosis. A more in depth understanding of cancer-stroma crosstalk within the tumor microenvironment and stroma based clinical and translational therapies may provide new therapeutic strategies for the prevention of pancreatic cancer progression.

Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems

Abstract: Fe3O4 nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe3O4 NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe3O4 NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe3O4 NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe3O4 NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe3O4 NPs targeting drug/gene delivery systems.