Week 02: Lecture 07: Introduction on Nanoparticles as Drug Delivery System-II

Main ideas and concepts (what the lecture covers)

• Context of the course
  • The speaker introduces an NPDL online certification course on novel drug delivery systems.
  • This lecture builds on earlier sessions covering:
    • What novel drug delivery systems are and why they matter
    • Types of nanoparticulate delivery systems
    • Key terminology/properties of nanocarriers
  • Today’s focus: advantages, limitations, drug delivery applications, landscape of nanomedicine, and a case study.

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Advantages of nanoparticle/nanocarrier drug delivery systems (key points)

• Improved therapeutic efficacy and safety

  • Due to small particle size, nanocarriers can enhance how well drugs work.
  • They can improve the safety profile of existing drugs.

• Surface modification for targeted delivery

  • Drugs/biomolecules (examples mentioned: proteins, peptides, siRNA, DNA) can be loaded into nanocarriers.
  • By modifying the surface with ligands (transcript indicates “lians/lignans”), the system can achieve specific targeting to body areas/cells.
  • Example for cancer targeting:
    • Use ligands such as transferrin and folate (and monoclonal antibodies mentioned)
    • After conjugation on the nanoparticle surface, they can target cancer cells.

• Route versatility (multiple administration routes)

  • Nanocarriers can be administered via:
    • Oral
    • Parenteral
    • Dermal
    • Pulmonary
    • Nasal
  • Size guidance mentioned:
    • Prefer < 100 nm
    • Formulations may sometimes be 200–500 nm, depending on context (as suggested by the lecturer).

• Enhanced solubility and stability

  • Using lipids and surfactants, along with reducing particle size, can:
    • Increase solubility
    • Improve stability
  • Particularly beneficial for poorly water-soluble drugs, especially BCS class 2 and class 4.

• Controlled/sustained drug release

  • Achieved using polymers, especially PLGA (poly(lactic-co-glycolic acid)).
  • Release duration examples:
    • Days to months
    • Longer-acting systems may extend to years (wording in transcript suggests “up to the years” for certain formulations).

• Dose reduction and reduced side effects

  • Increased solubility/efficacy can allow lower dosing.
  • Lower dose and less frequent administration can reduce side effects.

• Protection from degradation and longer circulation

  • Encapsulation protects drugs from degradation due to:
    • Acidic conditions
    • Enzymatic degradation
    • pH-related changes
  • This can enhance drug longevity in blood and increase T½ (half-life).

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Limitations of nanoparticle/nanocarrier systems (and mitigation strategies)

• Aggregation / poor colloidal stability

  • Cause: high surface area from nanoscale size can promote aggregation.
  • Mitigation: add stabilizers to improve colloidal stability.

• Limited drug loading and “burst release”

  • Observed especially with:
    • Liposomes
    • Hydrophilic-type carriers (as described)
  • Issues:
    • Low drug loading
    • Initial rapid release (“burst release”)

• Toxic solvents in inorganic/synthetic systems

  • Some inorganic nanocarriers and synthetic polymers may require toxic solvents for synthesis.
  • This can degrade sensitive drug molecules.
  • Mitigation direction (implied): choose appropriate materials/processing to avoid damaging solvents, including consideration of natural materials.

• Immune response / allergic reactions

  • Mentioned: inorganic nanoparticles and some formulations can trigger immune/allergic reactions.

• Oxidative stress and cellular damage (metal/inorganic nanoparticles)

  • Examples:
    • Silver nanoparticles
    • Gold nanoparticles
    • Iron oxide nanoparticles
  • Mechanism:
    • Release of species → reactive oxygen species (ROS) / free radicals
    • Leads to damage of DNA and proteins
  • Mitigation: take “required precautions during synthesis.”

• Poor biocompatibility and environmental hazards

  • Particularly noted for inorganic/metal nanoparticle systems:
    • Biocompatibility concerns
    • Environmental risks

• Scale-up and regulatory challenges

  • Compared to conventional systems:
    • Lack of well-established regulatory frameworks specifically for nano drug delivery
  • Scale-up challenges:
    • Reproducibility
    • Continuous production
  • Note mentioned: industries are working with regulatory bodies to resolve these issues.

• High manufacturing cost

  • Costs increase due to:
    • Expensive materials
    • Need for dedicated equipment and dedicated facilities

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Drug delivery and nanomedicine applications mentioned (organized)

• Antibacterial delivery (multidrug-resistant infections)

  • Nanocarriers can help treat multidrug-resistant infections by overcoming resistance pathways.

• Anticancer drug delivery

  • Encapsulate anticancer drugs into nanocarriers to inhibit growth of new cancer cells.
  • The lecture implies improved targeting and delivery to tumor sites.

• Brain targeting / neurological disorders

  • Applications include targeting:
    • Epilepsy
    • Psychiatric disorders

• Vaccine delivery and gene-related therapy

  • Antigen delivery using virosomes (mentioned as helpful for vaccine delivery).
  • Claimed benefits for nucleic-acid delivery (DNA, mRNA):
    • Protect nucleic acids from degradation
    • Improve stability and immune response
  • Mechanism described:
    • Complex nucleic acids with positive-charged lipids / positive charged polymers
    • Supports cell transfection
  • The process is described as gene therapy.

• Ocular, nasal, and pulmonary delivery

  • Nanocarriers can be used for these routes, improving safety/efficacy versus conventional systems.

• Molecular diagnosis / imaging (contrast agents)

  • Inorganic nanoparticles can act as contrast agents due to:
    • Optical properties
    • Physical properties
    • Responses to different light systems
    • Magnetic properties
  • Examples:
    • Iron oxide, silver, gold nanoparticles
  • Imaging modalities listed:
    • Ultrasound
    • Fluorescence
    • Nuclear imaging
    • Computed tomography (CT) (transcript text included “computerated topography”)

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Landscape / historical timeline of nanomedicine and liposome development (as described)

• 1964
  • First liposome discovered.
• 1976
  • First controlled release polymer systems developed.
• 1978
  • First “published denimer” mentioned (term unclear in transcript; likely relates to a polymeric/dendrimer-related item).
• Targeted liposomes introduced
  • Improvement phase noted between ~1964 and 1980.
• EPR effect
  • Scientists discovered/explained the EPR (enhanced permeability and retention) effect to support tumor targeting.
• Long-acting formulations
  • Improvement using polyethylene glycol (PEG) (PEGylation implied).
• 1995
  • First doxorubicin-loaded liposome approved.
• Later FDA-approved products
  • Multiple polymeric/lipid formulations referenced as approved.
  • Transcript included unclear mention: “polymeric myel… packlet axel” (likely relates to a paclitaxel formulation).
  • Clinical trials for targeted control release polymer nanoparticles mentioned around 2011.
• Inorganic nanoparticles
  • Used for MRI contrast applications.
• Overall development stages
  • Conceptualization → clinical validation → commercialization → expansion and refinement

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Case study: improving poorly soluble drugs via nanoformulation (methodology)

Problem identified

• Poorly water-soluble drugs (examples aligned to BCS class 2 or class 4)
  • Need improved:
    • Solubility
    • Bioavailability
    • Stability

Core approach

• Reduce particle size into the nano range
  • Benefit: increased surface area → enhanced water solubility
  • Enhanced solubility supports improved bioavailability
  • Lecture links bioavailability to rate-limiting factors:
    • solubility and permeability

Example processing method: high pressure homogenization

• Equipment/process described
  • Use high pressure homogenization
  • Pass microparticles through the instrument at high pressure
  • Result: particles reduced to the nano range
• Outcome described
  • Example:
    • ~3 µm particles reduced
    • “30-fold reduction” mentioned
  • Stabilizers can be used to improve final formulation stability.

Case study comparison experiments (dissolution and permeation)

• Lutein study (reference named)
  • Lutein described as water insoluble
  • Compared:
    • Native powder
    • Nano suspension produced via high pressure homogenizer
• Dissolution profile
  • Dissolution measured over time (up to a few hours; transcript indicates “up to 3 hours”).
  • Reported improvement:
    • approximately 25–30% to ~70% (exact values unclear due to subtitle errors; “almost near to 75% / 70% improvement” mentioned)
• Permeation across skin
  • Comparison described:
    • Native/ordinary form: < 5% permeation
    • Nano suspension: increased to about ~60% permeation
• Further dosage-form steps described
  • Nano suspension can be converted into lactobased pellets
  • Pellets are then filled into capsules
  • Goal: maintain improved solubility and permeability

General instruction implied by the case study

• For BCS 2 / BCS 4 drugs:
  • Convert to nano suspension using high pressure homogenization or other nanosizing techniques
  • Add stabilizers as needed
  • Then formulate into final solid dosage forms (e.g., pellets/capsules)

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Closing takeaway (what the lecture concludes)

• The lecture emphasizes:
  • Advantages of nanocarrier systems: targeting, solubility, controlled release, safety/dose reduction, protection from degradation
  • Limitations: aggregation, burst release, toxicity/immune issues, oxidative stress, biocompatibility/environmental concerns, scale-up/regulatory challenges, and cost
  • The case study shows how nanosizing improves dissolution and permeation, supporting better drug delivery.

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Speakers / sources featured

• Speaker/Instructor: Dr. Satish Dawanapelli, Assistant Professor, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai
• Sources referenced: A lutein study (specific citation details not provided in the subtitles)
• Named individuals/publications: No other clearly identified individuals or external publications in the transcript.