Week 02: Lecture 08: Polymer-based nanocarriers

Main Ideas & Concepts Covered

• Course context: The lecture is part of an NPDL online certification course on novel drug delivery systems and follows earlier lectures covering:

  • Nanoparticles as drug delivery systems
  • Nanomedicines: advantages/disadvantages
  • Drug delivery terminology
  • Types of nano-carriers by material class
  • Nanoparticle properties and applications (e.g., vaccines, gene therapy)
  • Limitations and a case study on pharmaceutical advances

• Today’s focus: Polymer-based nanocarriers (polymeric nanocarrier systems) as drug delivery systems.

Classification of Nano-carrier Systems (by Material)

1. Polymer-based nanocarriers
2. Lipid-based nanocarriers
3. Inorganic-based nanocarriers
4. Vesicular systems (examples mentioned: noomes, ethosomes, transfers, etc.)

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What Are Polymeric Nanoparticles?

• Size range: about 10 to 1000 nm
• Composition: made from polymers
• Role: vehicles that deliver drugs, genes, and other cargo to specific sites

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Polymers Used in These Systems

Natural Polymers

• Classified by source:
  • Polysaccharides: example given chitosan
  • Proteins: example given albumin
• Other examples mentioned: hyaluric acid, gelatin, gums

Synthetic Polymers

• Examples mentioned: poly lactic acid, polycaprolactone (as transcribed), polyethylene glycol, polyethylene amine

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Polymeric Nanoparticle Types (Structure-Based)

Nanospheres

• Matrix system where the drug is uniformly dispersed throughout the polymer matrix

Nanocapsules

• Reservoir system with:
  • Polymer shell (outside)
  • Core containing active molecules (inside)

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Key Properties / Advantages of Polymeric Nanoparticles

• Biodegradable & biocompatible

  • After administration, polymers undergo metabolism/degradation into monomers/degradable metabolites
  • Intended to avoid toxicity

• Surface modification potential

  • Surface can be modified using polymers like polyethylene glycol (PEG)
  • Further functionalization possible with ligands and monoclonal antibodies for targeted delivery

• Control over pharmacokinetics

  • Polymer nanoparticles can modulate absorption, distribution, metabolism, elimination (pharmacokinetic profile)

• Protection of drug cargo

  • Helps protect macromolecules from:
    • Enzymatic degradation
    • Acidic degradation (e.g., in GI tract / blood acidic conditions)
  • Particularly useful for enzyme- and acid-sensitive drugs

• Wide range of therapeutic payloads

  • Small molecules (pharmaceutical active ingredients)
  • Proteins and peptides
  • Vaccine antigens
  • DNA and siRNA delivery

• Regulatory / real-world example

  • US FDA approval of some biodegradable polymers for human use mentioned:
    • Poly(lactic acid)
    • Poly(lactic-co-glycolic acid) (PLGA; transcribed with errors)

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Advantages vs. Lipid/Nano Systems (As Stated)

• Simpler preparation

  • Described as straightforward solvent-based formulation with energy/mechanical input

• Higher stability

  • Lipids can suffer from oxidation and storage degradation
  • Polymers described as having better stability than liposomes

• Controlled / sustained release

  • Achieved by encapsulation and/or conjugation strategies

• Targeting example strategies

  • Conjugation with targeting ligands such as:
    • Folate
    • Transferrin
    • Monoclonal antibodies
  • For anti-cancer targeting (to cancer cells)

• Prolonged circulation time via PEGylation

  • PEG helps reduce opsonization and phagocytosis by the reticuloendothelial system
  • Leads to enhanced half-life and higher drug levels in blood

• Lower immunogenicity

  • PEGylation also helps reduce immune recognition (as stated)

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Preparation Methods (Detailed)

The lecture describes three prominent preparation methods for polymeric nano-formulations. It also notes that the exact method depends on:

• Polymer type
• Carrier type
• Active ingredient/drug type

1) Solvent Evaporation Method

• Solvents: use water-miscible / organic solvents such as methyl acetate or acetone (chosen due to lower toxicity profile mentioned)

• Prepare two phases:

  • Aqueous phase: water + surfactant
  • Organic phase: polymer + drug dissolved in the organic solvent

• Form an emulsion:

  • Mix the aqueous and organic phases (stirring)
  • Apply mechanical disruption/energy input to reduce size from micron → nano

• Remove solvent:

  • Evaporate the organic solvent
  • Emulsion converts to polymeric nanoparticle suspension

• Purification:

  • Remove:
    • unloaded/unencapsulated drug
    • unreacted polymer
    • excess surfactant

• Recovery and storage:

  • Wash
  • Collect by centrifugation
  • Freeze-dry (lyophilization) for long-term storage

• Freeze-drying (lyophilization) principle:

  • Uses sublimation to convert liquid formulation into a dry powder
  • Intended to prevent degradation from water and reduce microbial growth risks

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2) Emulsification–Solvent Diffusion Method

• Use two phases again:

  • Organic solution: polymer + drug + water-miscible organic solvent (example given: ethyl acetate)
  • Aqueous solution: water + surfactant

• Create emulsion:

  • Form emulsion similarly to the solvent evaporation approach
  • Use stirring, high-pressure homogenization, sonication, or high-shear homogenization (as options mentioned)

• Key difference from solvent evaporation:

  • Instead of evaporating the solvent, dilute with a large amount of water

• Solvent diffusion step:

  • The organic solvent diffuses out from the nanoparticles into the external medium

• Outcome:

  • Formation of colloidal polymeric nanoparticles

• Removal & purification:

  • Remove solvent and purify the particles

Extra note (as transcribed): Mentions a solvent example resembling dichloromethane and an outcome resembling “hollow microspear/nanospheres” (wording unclear due to subtitle errors)

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3) Nanoprecipitation Method (Solvent Displacement / Precipitation)

• General principle: precipitation of polymer when mixing polymer solution into a solvent system where polymer becomes insoluble

• Steps:

  • Dissolve polymer + drug in a water-miscible (organic) solvent
  • Inject very fastly and controlled drop-by-drop into an aqueous solution containing water + surfactant

• Mechanism:

  • Polymer precipitates upon mixing (subtitle mentions this method can occur without surfactant, depending on conditions)

• After precipitation:

  • Remove remaining solvent by solvent evaporation
  • Perform purification
  • Proceed to analysis

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Other Polymeric Nano-carrier Types Mentioned (Beyond Nanoparticles)

Polymeric Micelles

• Defined as core–shell nano-sized structures
• Formed by self-assembly of amphiphilic block copolymers
• Example triblock polymer: Pluronic
  • Structure described as having polyethylene oxide (PEO)-like hydrophilic segments at ends
  • and a polypropylene oxide (PPO)-like hydrophobic middle segment
• When dispersed in water, micelles self-assemble in aqueous medium

Dendrimers

• Nanosized, hyperbranched 3D polymer macromolecules
• “Tree-like” structure with:
  • core
  • branches
  • terminal functional groups
• Terminal groups allow:
  • conjugation/functionalization
  • altering surface properties
  • drug absorption at functional sites
• Claimed benefit: better cell membrane penetration than linear polymers
• Examples listed: poly(amidine), poly(propylene amine), poly(ether hydroxylamine), poly(lysine) (some names transcribed with errors)

Polymerosomes

• Described as tiny hollow spheres
• Made from synthetic self-assembly of amphiphilic block copolymers
• Clarified as not micelles
• Distinction described via structural organization (micelles vs “double-layer”/membrane-like vesicle concept, though subtitle wording is somewhat unclear)
• Examples mentioned as coming from dblock/triblock polymer systems

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Speakers / Sources Featured

• Dr. Dr. Satish Dawanapali, Institute of Chemical Technology, Mumbai (lecturer / presenter)