Controlled Delivery & Targeted Delivery Platform
Focus: High-Throughput Combinatorial Synthesis, Screening and Optimization Platform
Target: Drug Delivery System Development and Clinical Translation
Injectable (~ 55%) and oral (~ 33%) delivery are still the major drug delivery routes. Improving the targeting of the drug or drug-content cargo and developing on-demand delivery could dramatically improve the therapeutic efficiency and decrease the toxicity of the drug during the circulation of the drug in the bottom. To achieve these requirements, developing targeting strategies and investigating the drug-cargo interactions and cargo-cell interactions are essential. High-throughput manufacturing, characterization, screening and selection will provide a precise engineering strategy to develop and optimize a combinational drug delivery system, this will be efficient for the clinical translation of the drug delivery system. It includes high-throughput drug encapsulation and delivery material development, which provides efficient combinatorial library for optimizing structure-activity properties of the control-delivery cargos. It also includes the screening, selection and the evolution of the target-specific affinitive materials, such as affibodies, anticalins, adNectins, and aptamers, which improves the efficiency of the targeted delivery in the injection based or oral therapeutics. Finally, the high-throughput process includes the evaluation and optimization of the drug-delivery system performance in-vitro and in-vivo.
Figure 1. Hit and lead generation: beyond high-throughput screening (Source: Nature Reviews Drug Discovery 2, 369–378 (2003))
We provide high-throughput combinatorial synthesis, screening and optimization platform which includes the following key features:
- High-throughput drug encapsulation and delivery material (organic and inorganic) synthesis, modification and biophysicochemical property characterization assays development and commercialization
- Combinatorial and evolution-based methods of targeting tags screening, selection, and scale-up
- High-throughput characterizations of cell-specific endocytosis and endosomal colocalization of targeted drug-delivery systems
- High-throughput device manufacturing, optimization, in-vitro organ/tissue-model fabrication for high-throughput drug-delivery system screening, selection and evolution.
What We Do: Customized Encapsulation/Releasing Formulation
High-throughput Polymer Synthesis and Characterizations
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Development of the strategies of diversity-oriented synthesis and modifications of biocompatible and biodegradable polymers (homo, block, co-polymers), biomolecules (peptide, protein, DNA, RNA, polysaccharides and lipids), and inorganic nanoparticles (plasmonic, magnetic, upconversion NP).
1. Component variations (chemistry, ratio, sequence, main/side chain, structure)Read More
1.1 HT automated RAFT, ATRP or other free radical polymerization of vinyl based homopolymer, co-polymer, block-polymer could be performed in a Freeslate Semi–continuous Parallel Pressure Reactor (ScPPR). The combinational synthesized polymers could achieve solid, core-shell, worm-like nanoparticles, micelles, nano/micro particles. The applications will be gene delivery, general (hydrophobic, hydrophilic, amphiphilic) drug delivery, and anti-fouling substrate. The choice of the vinyl monomer could be: charged (Basic and Zwitterionic or Zwit), hydrophobic methacrylates (HPO MA), amines (Amines), aromatic (Aromatic), hetero ring (Hetero ring), monomers that do not easily fit into the other categories (Others), strong and weak acids (Acid), polyethylene glycols (PEGs) and hydroxyl monomers (Hydroxy).
1.2. Flow polymerizations
a. Continuous flow ring-opening polymerizations
b. Continuous flow system ATRP polymerizations
c. Anionic Polymerization Using Flow Microreactors
1.3. A HT combinatorial library of lipid-like materials synthesized by addition of acrylamides or acrylates to amines
1.4. A HT combinational library of degradable cationic polymer achieved by adding all possible pairwise combinations of amine and diacrylate monomers
2. Inorganic nanoparticle high-throughput fabrication (microfluidic based)Read More
2.1. Gold nanoparticles (millifluidic benchtop formulation: HAuCl4 + ligand + ancillary reagents + NaBH4 or AuNP seeds)
2.2. Magnetic nanoparticles high-throughput synthesis (FeCl3 in HCl + TMAOH)
2.3. Upconversion NP
a. Flow reactors for the combinatorial production of lanthanide-doped colloids.
b. Symyx CM2 laboratory automation robot for high-temperature nanocrystal synthesis
3. End group variationsRead More
3.1. Substrates’ functional end group modifications and kits development (e.g. mono/di/tri -OH, -NH2, -SH, -CHO, -COOH, -epoxy, -NHS, -Biotin, -alkyne, -azide, sulfo-SMCC)
4. Degradation rate controlRead More
4.1. Degradation options:
General hydrolysis rate: polyanhydride
Specific enzyme degradable: MMP, elastase
4.2. A high throughput combinatorial library of the polymer with various degradation rate achieved by microfluidic method of physical blending, or microarray based monomer combinational condensation polymerizations
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Customized fabrication of the devices for the high-throughput synthesis, modification and encapsulation (microarray based or microfluidic based device manufacturing, synthetic nanoliter-spotting techniques)
Figure 2. Top: Scheme of matrix based high throughput processing method. Bottom: Scheme of continuous flow based high throughput processing method.
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High-throughput encapsulation and analysis development
1. Nanoprecipitation/Microfluidic method: Amphiphilic polymer based NP(ACN + H2O) , lipid vesicle(IPA + H2O) , Hydrophobic NP(THF + H2O), Inorganic NP (precursor solution + reactant solution + H2O)
2. HT RNA Complexation Assay
3. Chemical drug encapsulation evaluation: drug diffusivity measurement
4. HT spray drying based water-insoluble drug encapsulation
5. Fluorescence anisotropy
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High-throughput material characterizations (microarray based surface analysis)
1. High-throughput NMR Assay
2. High-throughput FTIR Assay
3. Assays Based on UV/Visible Spectroscopy
4. Assays Based on Mass Spectrometry Enantiomers
5. Capillary Array Electrophoresis
6. AFM based high-throughput screening
7. Molecular weight (MALDI-TOF MS)
8. Component analysis (ATR-FTIR, Raman and infrared microspectroscopy)
9. Degradation rate (HPLC and MS)
10. XPS analysis provides a quantitative elemental composition (functional groups) from the top 10 nm of the surface
11. ToF-SIMS provides a qualitative assessment of chemical composition of the uppermost 1 - 2 nm of the outer surface
Screening, Selection, and Enriching In Vitro Evolution of the Target-specific Affinitive Materials
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High-throughput affinity based screening and selection
1. Miniaturization isothermal titration calorimetry (ITC), array calorimetry
2. surface plasmon resonance (SPR) microscopy
3. quartz crystal microbalance sensor array coupled with microfluidics, and
4. spectroscopic methods
5. Fluorescence anisotropy (measure the binding constants and kinetics of reactions that cause a change in the rotational time of the molecules)
6. Dual-polarization interferometry: The technique is quantitative and real-time (10 Hz) with a dimensional resolution of 0.01 nm.
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Computer-assisted design, analysis, and optimization (stochastic, deterministic, empirical, physics-based)
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Evolution of the affibodies, anticalins, adNectins, and aptamers
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High throughput side-effect targets screening and evaluation the targeting efficiency and side reaction possibility
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epitope tags development (Myc-tag, HA-tag, FLAG-tag, GST-tag, 6xHis, V5-tag and OLLAS. (Specifications: V5 Tag Antibodies, His-Tag Antibodies, DYKDDDDK Tag antibodies, Anti VSV-G Tag Antibodies, HA-Tag Antibodies, S-Tag Antibodies, C-Myc Tag Antibodies, Strep Tag Antibodies)
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Unnatural amino acid high throughput producing
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molecular imprinting
High-throughput Evaluation and Optimization of the Drug-delivery System In-vitro and In-vivo
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Development of 3D printed or micro-chip based tissue model for high-throughput evaluation of the drug delivery system
1. Organ-on-chip fabrications: 3D printing organs and microfluidic based organ-on-chip fabrications
2. HT Confocal Microscopy
High-throughput In-vitro Evaluation (Micro-array Based or Micro-fluidic Based)
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Label free detection
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Sensitivity enhancement
