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Week 03: Lecture 11: Nanostructured Lipid Carriers (NLCs)

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Key takeaways

Educational

Main ideas & lessons from the lecture (Week 03: Lecture 11 — Nanostructured Lipid Carriers, NLCs)

Where NLCs fit in lipid-based nanocarriers

The lecture is positioned in a progression of lipid nanocarriers:

  • 1st generation: Liposomes and Solid Lipid Nanoparticles (SLNs)
  • 2nd generation: Nanostructured Lipid Carriers (NLCs)

Why NLCs were developed (limitations of SLNs)

SLNs are limited by:

  • Drug leakage during storage → reduces drug loading over time
  • Unpredictable gelation tendency → can cause particle growth during storage
  • High crystallinity in SLNs → leads to lower drug loading after storage (via drug expulsion/crystallization effects)

Core concept: how NLCs improve performance over SLNs

NLCs are designed to provide:

  • Higher and more stable drug loading
  • Higher stability during storage
  • Controlled leakage

Key structural difference:

  • In SLNs, solid lipids form an ordered crystalline matrix.
  • In NLCs, solid lipids are blended with liquid lipids (oils), creating structural imperfections (less ordered crystals / gaps).

These imperfections increase drug accommodation and reduce drug expulsion.

Structural mechanism (the “imperfection” idea)

Adding liquid lipids (oils) into a solid lipid matrix:

  • disrupts crystal ordering
  • creates gaps/imperfections
  • allows more drug molecules to be loaded

Lecture contrast:

  • SLN: more ordered crystals → less space for drug → more leakage/crystallization-driven loss
  • NLC: less ordered (imperfect) crystals / amorphous regions → better retention → higher loading

Classification: Types of NLCs (3 main types)

1) Imperfect crystal NLCs (Type 1)

  • How they’re made (conceptual design):
    • Use high concentration of solid lipid relative to liquid lipid
    • Employ lipids with different chain lengths
    • Can involve mono- or triglycerides
  • Resulting structure:
    • The solid lipid does not pack perfectly → imperfect/less ordered crystals
  • Drug behavior:
    • Tends to show high drug loading
    • Drugs can be incorporated within the imperfect crystalline matrix

2) Amorphous (Type 2) NLCs

  • How they’re made:
    • Use medium-chain triglycerides with solid lipids
  • Resulting structure:
    • After cooling, formulation tends to avoid recrystallization
    • Forms an amorphous (non-crystalline) structure
  • Drug behavior:
    • Lack of crystal formation supports enhanced loading capacity
    • Reduces crystal-driven drug leakage

3) Multiple (Type 3) NLCs

  • How they’re made:
    • Use high liquid lipid content with less solid lipid
  • Resulting structure:
    • Oil nanocompartments (oil droplets/regions containing drug) dispersed within a lipid network
  • Drug behavior:
    • Especially suitable when:
      • drug has better solubility in oils (including hydrophobic drugs)
    • Oil regions help encapsulate drug molecules, while solid lipid surrounds/disperses them

Composition of NLCs (what must be chosen)

  • Solid lipid (solid at room and body temperature in principle)
  • Liquid lipid (oil)
    • provides structural imperfections and accommodates drug
  • Surfactant/emulsifier
    • stabilizes the emulsion and helps form nanoscale particles
  • Drug selection depends on:
    • Drug solubility
    • Drug properties (lipophilic vs hydrophilic; permeability/solubility issues)

Methods of preparation (and how they relate to SLN methods)

High-level workflow (similar to SLN, with an added lipid step)

  • Lipid phase preparation:
    • melt the solid lipid
    • add liquid lipid (oil)
    • add the active drug
    • add solvents if needed
  • Water phase preparation:
    • prepare the aqueous phase
    • add emulsifier/surfactant to water
  • Emulsification + particle formation:
    • combine lipid phase into water phase (or vice versa) to form emulsion
    • select equipment/process conditions based on chosen technique
  • Cooling/solidification:
    • cool down the system to form nanostructured lipid carriers (solid/semi-solid lipid matrix)

Preparation techniques mentioned (category-level)

  • High-energy techniques (energy input to reduce particle size, similar to SLN approaches):
    • High pressure homogenization
    • Ultrasonication
    • High-speed homogenation
    • Supercritical fluid method
  • Low-energy / simpler emulsification approaches
    • contrasted with high-energy approaches
    • exact low-energy steps were not detailed

Applications highlighted for NLCs

Routes of delivery (explicitly mentioned)

  • Oral
  • Topical
  • Ocular
  • Intranasal / Nose-to-brain
  • Parenteral (intravenous/injection context)
  • Pulmonary (respiratory delivery, including COPD and COVID-related antiviral context)
  • Skin (percutaneous) — focus of the case study

Drug/Biopharmaceutics suitability (BCS-based points)

NLCs can be used when drugs face solubility/permeability limitations:

  • BCS class 2: limited solubility → improve water solubility
  • BCS class 3: high hydrophilicity but low permeability → improve permeability
  • BCS class 4: limited by both solubility and permeability → can address both concerns
  • Class 1 is mentioned as needing balance of solubility and permeability, but not as the primary claim

Also noted: NLCs can improve bioavailability and penetration depending on drug class and route.

Case study: NLCs vs SLNs for percutaneous delivery of an alkaloid extract

Purpose

Compare:

  • nanostructured lipid carriers (NLCs)
  • vs solid lipid nanoparticles (SLNs)

for percutaneous administration of an alkaloid extract.

Why the drug choice matters

The alkaloid actives undergo metabolic degradation, causing low bioavailability. Carriers were used to improve delivery and bioavailability.

Method overview (as described)

Authors prepared:

  • an SLN formulation
  • an NLC formulation

Both were produced at the nanoscale using high pressure homogenization, targeting comparable particle size.

Key comparative results

  • Particle size:
    • NLC ≈ 160 nm
    • SLN ≈ 176 nm
    • sizes are similar, supporting a fair comparison
  • Drug loading:
    • both achieved >75% drug loading
  • Skin penetration enhancement:
    • NLCs showed ~3.2 to 27-fold higher penetration vs SLNs
  • Interpretation of the figure described:
    • one curve (blue) = SLN penetration vs time
    • another curve (pink) = NLC penetration vs time
    • the NLC curve remains consistently much higher across time intervals

Conclusion from the case

Higher retention/loading and NLC structural advantages lead to:

  • better penetration
  • improved bioavailability of the delivered active

Speakers / sources featured

  • Dr. Satish Dawapelli — Assistant Professor, Department of Pharmaceutical Science and Technology, Institute of Chemical Technology, Mumbai
  • Unspecified authors of the referenced open-access case study paper (no names provided in the subtitles)

Original video