nanoparticles - polymeric and liposomes

Lecture 4: Polymeric Nanoparticles and Liposomes

Overview

  • Polymeric Nanoparticles (NP)

    • Continued exploration of types and applications.

    • Discussion of Solid Lipid Nanoparticles (SLNs).

    • Approaches in NP manufacturing.

    • Summary of nanoparticle types.

    • Applications of polymeric nanoparticles.

  • Liposomes

    • Introduction to liposomes, including formation and types.

    • Preparation methodologies.

    • Overview of liposomal drugs.

    • Advantages and limitations of liposomes.

Blood Drug Concentration vs Time

  • Importance of controlled drug release.

  • Hydrogels used in drug delivery:

    • Definition: Elastic three-dimensional polymer networks swollen by water.

    • Ability to establish controlled drug release by modifying polymer matrix structure.

    • Drug effect linked to concentration and duration at target sites.

Polymeric Nanoparticles (Continued)

Solid Lipid Nanoparticles (SLNs)

  • Introduction:

    • Developed in the early 1990s.

    • Offered as alternative carriers to emulsions, liposomes, and polymeric nanoparticles.

    • Size Range: Sub-micron colloidal carriers (10 - 1000 nm).

    • Composed of physiological lipids dispersed in water or aqueous surfactant solutions.

  • Unique Properties:

    • Small size contributes to a larger surface area and high drug loading capacity.

    • Interactions at the interface valuable in cosmetic applications.

Advantages of SLNs

  • Encapsulation in solid lipid matrix protects against:

    • Chemical degradation.

    • Modulation of drug release profiles for sustained release.

  • Production capabilities:

    • Large scale without organic solvents.

    • Long-term stability (generally over a year).

    • High drug payload capacity and stability post-sterilization or lyophilization.

  • Several SLNs approved for human pharmaceutical applications.

Manufacturing Approaches for Polymeric Nanoparticles

  • Assembly Methods:

    • Covalent Assembly and Supramolecular Assembly.

    • Polymeric blocks types: Dendrimers, brushes, hyperbranched polymers, and block copolymers.

    • Chemical modifications available through ligand modification, core/shell crosslinking, and drug loading.

Bottom-Up Assembly Example

  • Description of Schematic illustration for:

    • Fully synthetic extracellular vesicles formation [Reference: Sciences Advances, 2021].

    • Mechanical emulsification leading to miRNA-containing lipid vesicles decorated with surface proteins.

    • Types of vesicles: Small Unilamellar Vesicles (SUV) and Giant Unilamellar Vesicles (GUV).

Applications of Polymeric Nanoparticles in Pharmacy and Medicine

  • Common uses include:

    • Implants.

    • Oral drug delivery systems.

    • Photochemical controlled drug delivery systems.

    • Ocular and nasal administration.

    • Other internal/external applications.

Liposomes

Definition and Historical Context

  • What are Liposomes?

    • Vesicles with one or more lipid bilayers enclosing aqueous compartments.

    • First observed by Bangham et al. in 1965, demonstrating the properties of phospholipid vesicles.

Formation of Liposomes

  1. Mechanism:

    • Lipid molecules (hydrophilic head, hydrophobic tail) self-assemble into bimolecular leaflets when solubility decreases.

    • Headgroups face aqueous phase; hydrocarbon tails shielded.

  2. Energy Requirement:

    • Energy from methods like shaking, sonication, or homogenization required for alignment into bilayers.

Classification of Liposomes by Size and Bilayers

  • Unilamellar Vesicles: Characterized by a single lipid bilayer.

  • Oligolamellar Vesicles: Transformation from unilamellar to bilayer vesicles possible through polymers.

  • Multilamellar Vesicles: Comprising several bilayers, vary physically and chemically from unilamellar vesicles.

Various Liposomal Hybrid Systems

  • Examples:

    • Conventional liposomes, Single-layer liposomes, Double-layer liposomes, Multilayered liposomes.

    • Biopolymer incorporation into liposomes and liposome-in-hydrogel systems.

Types of Liposomal Vesicles

  • Multilamellar Vesicles: 500-5000 nm, consist of concentric bilayers.

  • Immunoliposomes: Carrying antibodies that bind to specific antigens.

  • Small Unilamellar Vesicles: Approx. 100 nm size, single bilayer.

  • Large Unilamellar Vesicles: Range from 200-800 nm.

  • Long-Circulating Liposomes: Modified to prolong blood circulation through polymer grafting.

Preparation of Liposomes

  • Four major methodologies including:

    • Dry lipid film methods, emulsions.

    • Methods involving micelles, solvent injection, shaking, sonication, and homogenization.

  • Size classifications:

    • Small (SUVs), Large (LUVs), and Giant vesicles.

Liposomal Drugs

  • Lipid Bilayer Composition:

    • Comprised of phospholipids, PEG chains, entrapping hydrophilic and hydrophobic drugs.

Biological Properties of Liposomes

  • Attractive Features:

    • Biocompatibility, modifiable surface traits (size, charge).

    • Ability to entrap both hydrophilic and hydrophobic pharmaceuticals.

    • Protects drugs from external degradation while facilitating targeted delivery to cells.

Challenges in Liposomal Stability

Physical Stability

  • Colloidal behavior in water leads to aggregation and sedimentation.

  • Addition of charged lipids mitigates aggregation by inducing particle repulsion.

Chemical Stability

  • Two major types of lipid degradation:

    1. Lipid Peroxidation: Susceptibility due to unsaturated acyl chains. Mitigation includes selecting sources of lipids with saturation, use of antioxidants, and light-resistant packaging.

    2. Lipid Hydrolysis: Leads to free fatty acids and lyso-lecithin; reduced by proper lipid source selection and optimal pH.

Biological Stability

  • Rapid release of encapsulated molecules in contact with blood, primarily due to interactions transferring lipids to plasma proteins.