Study on the molecular design, release mechanism and clinical translation of nanocellulose-based drug sustained-release carrier

Study on the molecular design, release mechanism and clinical translation of nanocellulose-based drug sustained-release carrier

1. Structural characteristics of nanocellulose and the molecular basis of drug loading

1.1 Crystal structure and surface chemistry of nanocellulose

The drug-carrying capacity of nanocellulose is closely related to its crystal structure and surface chemical groups:

• Cellulose Iβ crystal form (mainly found in plant-source nanocellulose): has a highly ordered hydrogen bond network, suitable for physical adsorption of drug molecules

• Amorphous zone (accounting for 30-50% of cellulose nanofibers): can be used as a storage for drug embedding to increase drug loading

• Surface functional groups:

• Hydroxyl group: The drug can be covalently linked through esterification and etherification reactions

• Carboxylic (TEMPO oxidation introduction): Enhances water solubility and is used for pH response release

• Sulfate group (acid hydrolysis residue): drug loaded by electrostatic action

Table 1: Comparison of physical and chemical properties of different nanocelluloses

1.2 Molecular mechanism of drug loading

1. Physical adsorption

• Hydrogen bonding: Polar groups in drug molecules form hydrogen bonds with the hydroxyl groups of nanocellulose

• Hydrophobic interaction: Non-polar drugs can be embedded in the amorphous region of cellulose nanofibers

• Electrostatic adsorption: Positively charged drugs combine with negatively charged cellulose nanocrystals

1. Chemical coupling

• Covalent linkage: Form an amide bond with amino-containing drugs by activating carboxyl groups

• Dynamic covalent bonds: borate bonds for glucose-responsive insulin release

2. Drug release kinetics and stimulus response mechanisms

2.1 Release dynamics model

• Zero-order release: controlled release of pore diffusion of bacterial nanocellulose

• Higuchi model: Drug diffusion dominance of cellulose nanocrystals

• Korsmeyer-Peppas model: Super Case II forwarding when n value is greater than 0.89

2.2 Molecular design of stimulus-responsive release

1. pH Response System

• Mechanism: Protonation of carboxyl groups at low pH leads to weakening of electrostatic effects

• Experimental verification: Simulate the release difference in gastric juice and intestinal fluid

1. Enzyme triggered release

• Cellulase response: Enzyme secreted by colon bacteria degrades bacterial nanocellulose

• MMP-2 response: Cellulose nanofiber graft cleavable peptide

1. Redox response

• Disulfide bond: breakage in tumor hyperglutathione environment

3. Application cases and efficacy optimization

3.1 Anti-tumor treatment

Case 1: Cellulose nanocrystals targeted by folic acid receptors-doesorbacterium

• Construction: Folic acid is coupled to cellulose nanocrystals through polyethylene glycol spacer

• Efficacy: 78% reduction in tumor volume in mice

Case 2: Photothermal and chemotherapy collaborative system

• Support: Cellulose nanofiber filaments/polydopamine composite hydrogel

• Results: The tumor was completely ablated under laser irradiation

3.2 Oral drug delivery system

Case: Colon-targeted cellulose nanofiber filaments-methotrexate

• Design: Cellulose nanofiber fiber coated alginate microspheres

• Results: The concentration of colonic drugs in the rat model is 20 times that of the stomach

4. Clinical Translation Challenges and Solutions

4.1 Key Bottlenecks

1. Large-scale production:

• The waste acid treatment cost of cellulose nanocrystalline acid hydrolysis is high

• Long fermentation cycle of bacterial nanocellulose

2. In vivo safety:

• Cellulose nanocrystals accumulate in the liver after intravenous injection

• Lack of long-term toxicity data

4.2 Breakthrough path

• Process optimization: Preparation of homogeneous cellulose nanofiber filaments by microfluidic control technology

• Functional improvements:

• Introducing hyaluronic acid coating to reduce macrophage phagocytosis

• Gamma ray sterilization after drug loading

5. Future Outlook

• Genetic drug delivery: Cellulose nanofiber/CRISPR-Cas9 complex

• Self-oxygen supply system: cellulose nanocrystals supported catalase

• AI-assisted design: Machine learning predicts drug-carrier binding energy

Table 2: Nanocellulose drug carriers that have entered clinical research