Comprehensive Pharmaceutical Sciences Review: Nanoparticles, Surfactants, Colloids, Interfacial Phenomena, and Parenterals

Flashcard deck covering Nanoparticles, Surfactants, Colloids, Interfacial Phenomena, and Parenterals for PHRM 724.

Big Idea of Nanoparticles

Nanoparticles are colloidal systems engineered to change where, how fast, and how safely drugs are delivered in the body.

Colloid-to-Nanoparticle Translation Rule

A nanoparticle is not automatically "better"; it is useful only when the carrier solves a real formulation or delivery problem.

Formulation Problems Solved by Nanoparticles

Improved apparent solubility, protection from degradation before target site, altered biodistribution, reduced exposure to sensitive tissues, controlled release, and delivery of biological cargo.

Liposomes

Phospholipid vesicles capable of carrying both hydrophilic and lipophilic drugs.

Lipid Nanoparticles (LNPs)

Lipid-based nanoparticle platforms critical for the intracellular delivery of fragile nucleic acid cargo like mRNA or siRNA.

Polymeric Nanoparticles / Micelles

Matrices or self-assembled polymeric carriers used to encapsulate and deliver active therapeutic molecules.

Albumin-Bound Nanoparticles

Protein carrier systems where drug molecules are associated with albumin to improve formulation of poorly soluble drugs.

Polydispersity Index (PDI)

A measure reflecting the width of the particle size distribution; lower PDI indicates uniform particles, while higher PDI indicates a broader, heterogeneous population.

Particle Size / PDI Significance

Design variable that controls blood circulation, tissue penetration, cellular uptake, and formulation reproducibility.

Surface Charge Significance in Nanoparticles

Influences particle stability, electrostatic repulsion, protein adsorption, and cellular interactions.

Surface Coating (PEG/Polymer Layers)

Polymer layers applied to nanoparticle surfaces to reduce aggregation, prevent protein adsorption, and alter systemic clearance.

Drug Loading

The measure of how much drug is carried per nanoparticle unit, determining dose, formulation volume, and manufacturing feasibility.

Doxil®

PEGylated liposomal doxorubicin approved in 1995 that changes drug distribution and reduces toxicity profile.

Abraxane®

Albumin-bound paclitaxel nanoparticles approved in 2005 that improve the formulation of poorly soluble paclitaxel.

VYXEOS®

Liposomal daunorubicin and cytarabine approved in 2017 that maintains a fixed drug ratio inside a single carrier.

Onpattro®

Lipid complex/LNP siRNA formulation approved in 2018 that protects and delivers nucleic acid cargo.

Comirnaty®

An mRNA lipid nanoparticle vaccine approved in 2020 that enables cellular delivery of mRNA.

Active Targeting

Functionalizing nanoparticle surfaces with targeting ligands (such as antibodies, peptides, or aptamers) to bind specific overexpressed cell surface receptors.

Active Targeting Limitation

Active targeting does not guarantee delivery to the target tissue; it improves cell binding and uptake only after the particle has reached the target tissue.

Protein Corona

A layer of blood plasma proteins that coats the surface of a nanoparticle after it enters circulation, altering its biological identity.

Endosomal Escape

The process by which internalized nanoparticles disrupt the endosomal membrane (at pH $\thicksim 5-6$) to release intact nucleic acid or drug cargo into the cytosol.

Five Nanoparticle Formulation Checks

1. Size/PDI, 2. Zeta potential, 3. Drug loading, 4. Release + stability, 5. Sterility/route.

Nanoparticle Formulations Interchangeability

Nanoparticle formulations change pharmacokinetics, tissue distribution, efficacy, and toxicity, meaning they are not necessarily interchangeable with conventional formulations.

Parenteral Nanoparticle Routes

Administration via Intravenous (IV) or Intramuscular (IM) injection.

Pulmonary Nanoparticle Delivery

Administration of nanoparticles via inhalation into the respiratory tract.

Nasal Nanoparticle Delivery

Mucosal administration of nanoparticles through the nasal passages.

Cutaneous Nanoparticle Delivery

Administration of nanoparticles using microneedles or topical delivery systems across the skin.

Nanoparticle Characterization Sequence

Nanoparticle characterization $\rightarrow$ formulation design $\rightarrow$ clinical performance.

Passive Targeting

Altered biodistribution driven by physical anatomical or physiological characteristics without surface ligand modifications.

Ionizable Lipids in LNPs

Lipids inside LNPs that facilitate nucleic acid complexation, endosomal membrane disruption, and cytosolic cargo release.

Macrophage Clearance of Nanoparticles

Recognition and engulfment of circulating nanoparticles by phagocytic cells of the reticuloendothelial system.

Case A: Poorly Soluble Small-Molecule Drug

Solved by albumin-bound or micellar nanoparticle systems to overcome water solubility limitations or problematic excipients.

Case B: Cytotoxic Drug with Dose-Limiting Toxicity

Solved by liposomal encapsulation or PEGylation to alter systemic distribution and protect healthy tissues.

Immediate Release Profile

Release profile demonstrating rapid drug availability immediately following administration.

Sustained Release Profile

Release profile maintaining therapeutic drug levels continuously over an extended period.

Delayed Release Profile

Release profile showing minimal initial drug release followed by substantial release at a later time.

Biological Cargo Examples

Therapeutic molecules including mRNA (for protein expression), siRNA (for gene silencing), proteins, or vaccine antigens.

Nanoparticle Storage Instability Risks

Tendency of nanoparticles to aggregate, coalesce, or lose integrity during storage or after fluid dilution.

Nanoparticle Platform Classification Criteria

Nanoparticles are classified primarily by the material they are made of and their structural architecture.

Effect of Architecture on Delivery

Particle architecture directly affects drug loading capacity, release kinetics, physical stability, and suitable administration route.

Clinical Evaluation Core Question

What does the nanoparticle carrier change about the drug, and how does that affect efficacy, safety, or dosing for the patient?

Retained Colloid Properties in Nanoparticles

Large interfacial area from small size, Brownian motion preventing settling, and surface charge/zeta potential controlling stability.

Receptor-Mediated Endocytosis

The primary mechanism by which targeted nanoparticles or LNPs gain entry into target cells.

Batch-to-Batch Consistency Control

Achieved through rigorous control of size distribution, PDI, drug loading, and surface charge during manufacturing.

Three Meanings of Targeted Delivery

Altered biodistribution, specific ligand-receptor binding, or direct route/device placement.

Surfactant (Surface Active Agent)

A molecule or ion that amphiphilically adsorbs at an interface to lower interfacial tension or surface energy.

Amphiphile

A molecule possessing affinity for both polar (water) and non-polar (oil/organic) solvents.

Hydrophilic Surfactant

A surfactant with a predominantly water-attracting structure and high HLB value.

Hydrophobic Surfactant

A surfactant with a predominantly oil-attracting structure and low HLB value.

Surfactant Interfacial Location

Surfactants reside at an energy minimum at the interface between dispersed phases.

O/W Emulsion Surfactant Selection

To formulate an oil-in-water (O/W) emulsion, choose a surfactant that orients most of the molecule in the continuous water phase.

W/O Emulsion Surfactant Selection

To formulate a water-in-oil (W/O) emulsion, choose a surfactant that orients most of the molecule in the continuous oil phase.

HLB System

Hydrophilic-Lipophilic Balance system measuring a surfactant's relative preference for oil or water.

High HLB Value Meaning

Indicates a more hydrophilic surfactant suitable for formulating O/W emulsions, detergents, and solubilizers.

Low HLB Value Meaning

Indicates a more lipophilic surfactant suitable for W/O emulsions and antifoaming applications.

HLB Range: 1–3

Antifoaming agents.

HLB Range: 3–6

W/O emulsifying agents.

HLB Range: 7–9

Wetting agents.

HLB Range: 8–18

O/W emulsifying agents.

HLB Range: 13–15

Detergents.

HLB Range: 15–16

Solubilizers.

Wetting Agent Definition

A surfactant that, when dissolved in water, lowers the contact angle between the liquid and a solid surface.

Wetting Mechanism

Involves adsorption of surfactant molecules at the solid-liquid interface.

Contact Angle and Wetting Relationship

A small contact angle indicates good/excellent wetting, whereas a large contact angle indicates poor wetting.

Quaternary Ammonium Surfactants Action

Adsorb to bacterial cell surfaces and increase the leakiness of bacterial cell membranes, leading to cell rupture.

Physiological Function of Lung Surfactant

Secreted by the lungs to reduce surface tension at the air-alveoli interface, preventing alveolar collapse during respiration.

Emulsions (Dispersed System)

A liquid-in-liquid dispersed system stabilized by surfactants.

Suspensions (Dispersed System)

A solid-in-liquid dispersed system where solid particles are distributed throughout a liquid phase.

Aerosols (Dispersed System)

A solid or liquid phase dispersed in air.

Role of Surfactants in Dispersions

Surfactants lower interfacial tension/energy to stabilize inherently unstable dispersed systems.

Emulsion Energy Minimization Formula

$dG = \text{γ} \times \frac{}{}\text{δ}A$ where lowering interfacial tension ($\text{γ}$) lowers free energy stored in an emulsion.

Detergent Action

Surfactants that lift dirt/grease from surfaces by forming soluble micellar aggregates around hydrophobic soil.

Balanced Surfactant

A surfactant possessing approximately equal hydrophilic and lipophilic properties.

Alveolar Lumen

The internal cavity of the lung alveolus lined with a thin layer of natural pulmonary surfactant.

Contact Angle at $\text{α} = 0^\text{o}$

Indicates complete spreading of a liquid on a surface.

Contact Angle at $\text{α} < 90^\text{o}$

Indicates good wetting of a solid surface by a liquid.

Contact Angle at $\text{α} \text{≥} 90^\text{o}$

Indicates incomplete or poor wetting of a solid surface by a liquid.

Contact Angle at $\text{α} > 180^\text{o}$

Indicates complete absence of wetting (no wetting).

Surfactant Polar Head

Hydrophilic region of a surfactant molecule that interacts favorably with water.

Surfactant Nonpolar Tail

Hydrophobic hydrocarbon region of a surfactant molecule that interacts favorably with oil or organic phases.

Colloid Particle Size Range

Particles ranging approximately from $1\text{\thinspace}nm$ to $500\text{\thinspace}nm$ ($< 0.5\text{\thinspace}\text{μm}$).

Interfacial Effect in Colloids

Because small colloidal particles create a huge total surface area, surface/interfacial energy effects dominate physical behavior.

Colloidal Free Energy Equation

$dG = \text{γ} \times \text{δ}A$ showing that increased surface area ($\text{δ}A$) increases free energy ($dG$).

Lyophilic Colloids

Solvent-liking systems with strong interactions between the dispersed phase and dispersion medium; thermodynamically stable (e.g., gelatin in water).

Lyophobic Colloids

Solvent-hating systems with poor interactions between the dispersed phase and dispersion medium; thermodynamically unstable (e.g., inorganic particles or charcoal in water).

Association Colloids

Thermodynamically stable colloidal systems formed by aggregates of amphiphilic ions/molecules (e.g., micelles formed by detergents above CMC).

Three Major Categories of Colloidal Properties

Optical properties, Kinetic properties, and Electrical properties.

Tyndall Effect

The optical property where colloidal particles scatter a beam of light passing through them; true molecular solutions generally do not scatter light.

Brownian Movement

The continuous, random, erratic motion of colloidal particles caused by uneven bombardment/collisions with molecules of the dispersion medium.

Significance of Brownian Motion

Prevents gravitational settling in colloidal dispersions, keeping small particles suspended.

Fick's First Law of Diffusion Equation

$J = -D \times \frac{dc}{dx}$ where $J$ is diffusion flux, $D$ is diffusion coefficient, and $\frac{dc}{dx}$ is concentration gradient.

Negative Sign in Fick's Law

Indicates that diffusion occurs spontaneously down a concentration gradient, from high to low concentration.

Stokes-Einstein Equation

$D = \frac{kT}{6\text{π}\text{η}R}$ relating diffusion coefficient ($D$) to Boltzmann constant ($k$), temperature ($T$), viscosity ($\text{η}$), and hydrodynamic radius ($R$).

Effect of Particle Size ($R$) on Diffusion Rate

Increasing particle size ($R$) decreases the diffusion coefficient ($D$) and slows diffusion.

Effect of Temperature ($T$) on Diffusion Rate

Increasing absolute temperature ($T$) increases the diffusion coefficient ($D$) and accelerates diffusion.

Effect of Viscosity ($\text{η}$) on Diffusion Rate

Increasing viscosity ($\text{η}$) of the dispersion medium decreases the diffusion coefficient ($D$) and slows diffusion.

Colloidal Surface Charge Origins

Acquired via ionization of surface functional groups or selective adsorption of dissolved ions/molecules.

Counterions

Dissolved ions in solution that possess a charge opposite to that of the colloidal particle surface.

Similions (Co-ions)

Dissolved ions in solution that possess the same charge polarity as the colloidal particle surface.

Diffuse Double Layer (DDL)

The region surrounding a charged colloidal particle consisting of tightly bound surface/Stern layer ions and a diffuse outer region enriched with counterions.