Polymer Drug Delivery Systems Quiz

Introduction

• Drug concentration in the blood plasma does not remain constant; it fluctuates between the maximum therapeutic concentration (MTC) and minimum effective concentration (MEC).
• This fluctuation can lead to either toxic side effects from excessively high drug levels or lack of efficacy from insufficient levels.
• Frequent dosing is required to maintain therapeutic plasma levels for drugs with short half-lives, leading to poor patient compliance and unwanted side effects.
• Controlled drug delivery aims to deliver the drug at a predetermined rate, either locally or systemically.

Polymer Crystallinity

• Polymer crystallinity refers to the degree of ordered crystalline regions within a polymer.
• Polymers rarely achieve 100% crystallinity; they are typically semi-crystalline.
• Only amorphous regions are permeable to water molecules and other substances.
• Crystallinity affects a polymer's mechanical strength, swelling, and rates of hydrolysis and biodegradation.
• A lower degree of crystallinity corresponds with higher macromolecular chain mobility, leading to faster drug release.

Polymer Glass Transition

• Tg is the temperature at which a polymer transitions from a glassy state to a rubbery state.
• Tg is typically determined using differential scanning calorimetry (DSC).
• Below Tg, the polymer is glassy with limited mobility and slow diffusion rates.
• Above Tg, the polymer is rubbery, enabling improved water penetration and drug diffusion.
• A balance between amorphous and crystalline regions is essential for drug delivery applications.

Polymer Hydrophilicity/Hydrophobicity

• Solubility is a critical factor in drug delivery system design.
• Solubility depends on the chemical nature, structure, and crystallinity of the polymer.
• Hydrophobic polymers exhibit drug release controlled by surface erosion.
• Hydrophilic polymers may degrade via bulk erosion.
• Mixing hydrophilic and hydrophobic polymers can increase pore formation, accelerating polymer degradation and drug release.

Biodegradable Polymers

• Biodegradation is the breakdown of polymers by cellular or in vivo biological processes into nontoxic byproducts, like water and carbon dioxide.
• Most biodegradable polymers used in drug delivery applications utilize hydrolysable ester bonds.
• Biodegradable polymers have advanced drug delivery, medical devices, tissue engineering, and biomaterials.

Biocompatibility

• Biocompatibility means a material does not produce toxic or harmful effects on biological systems.
• Good biocompatibility does not automatically ensure good biodegradability.

Commonly Used Biodegradable Polymers

• Poly(glycolic acid) (PGA), Poly(lactic acid) (PLA), and Poly(lactic-co-glycolic acid) (PLGA) were among the earliest synthetic biodegradable polymers, used as sutures.
• Poly(ε-caprolactone) (PCL) is another well-known FDA-approved material, noted for its slow degradation rates.
• Other polymers include Poly(ortho esters) (POE), Poly(anhydrides), Poly(amides), and various copolymers.

Polymer Molecular Weight

• Low molecular weight (MW) polymers degrade more rapidly.
• MW significantly impacts drug release profiles and biological properties of polymeric drug delivery systems.
• Lower MW leads to smaller nanoparticles, influencing drug release kinetics, circulation, and accumulation in organs.

PLGA Polymers

• PLGA is a polyester with linkages in its carbon backbone, commonly employed due to its prolonged degradation.
• It's prepared via ring-opening polymerization of cyclic lactide and glycolide monomers.
• Variables like MW and the ratio of lactide-to-glycolide (L/G) affect its degradation rate.

PLGA Copolymers/PEGylation

• PEGylated PLGA (PLGA-PEG) copolymers enhance circulation times and biocompatibility by creating a steric barrier.
• Triblock PLGA-PEG-PLGA copolymers form viscous gels at physiological temperatures, offering temperature-sensitive drug delivery.

Polycaprolactones (PCL)

• PCL is an aliphatic polyester made from ε-caprolactone, used as a slow-release scaffold in tissue engineering.
• Having a low glass transition temperature (Tg), it remains semi-rigid at room temperature.
• Modifications of PCL with other polymers improve degradation and reactivity.

Polyamides

• Poly(amino acids) deliver low-molecular-weight drugs, are relatively nontoxic, and generally degraded by enzymes.
• Degradation rate is influenced by the hydrophilicity of the contained amino acids.
• Examples include poly(γ-glutamic acid) and poly(L-lysine).

Polymeric Micelles

• Formed when amphiphilic block copolymers self-assemble in aqueous media.
• Characterized by a core-shell structure and narrow size distribution (10-100nm).
• Lower critical micelle concentration (CMC) value contributes to greater stability and reduced dissociation in the bloodstream.

Advantages of Polymeric Micelles

• Enhancing solubility for hydrophobic drugs.
• Prolonged circulation times due to a hydrated "stealth" polymer surface.
• Minimizing renal excretion due to large size.
• Active and passive targeting capabilities.

Fabrication Techniques

• Several methods for encapsulating therapies in polymeric nanoparticles (NPs).
• Methods depend on drug and polymer properties and desired NP characteristics.
• Some fabrication techniques include bottom-up (emulsion, polymerization, precipitation) and top-down (nanoprecipitation, emulsification).

Mechanisms of Drug Release

• Mechanisms of drug release from polymeric systems include diffusion through water-filled pores, diffusion through the polymer matrix, and erosion.
• These mechanisms may be surface or bulk dependent.

Drug Release Profiles

• Drug release from polymeric NPs commonly follows a triphasic pattern consisting of a burst release phase, a slow release phase, and a faster release phase as degradation proceeds.

Macromolecular Drug Delivery Systems

• Generally use nondegradable (silicone, polyurethanes) for initial delivery systems.
• Macromolecular systems often rely on diffusion and degradation of the matrix.

Norplant I/II

• Norplant I, an example, used six silicone capsules implanted in the upper arm for progestin delivery (hormonal birth control).
• Later versions (Norplant II) used improvements to control the release using slightly different polymers.

Ocusert, Progesterone, and Transderm Scop

• Ocusert is an ocular implant delivering pilocarpine, a drug for glaucoma.
• The sustained release was achieved using PEVA.
• Progesterone IUD (Intrauterine Device) and Transderm Scop (the first skin-patch for scopolamine, an anti-nausea drug) are examples of macroscopic polymeric drug delivery devices.

OROS

• OROS is an oral polymeric system for sustained drug delivery.
• Water absorption creates osmotic pressure for drug release.

Geomatrix

• Geomatrix is a controlled drug delivery system formed from hydroxylpropyl methylcellulose (HPMC), used to tailor drug release via layered swelling, gelling, and erosion rate control.

Microscale Polymeric Drug Delivery Systems

• Examples include PLGA microparticles used to treat prostate cancer by delivering luteinizing hormone-releasing hormone (LHRH).
• This system resulted in slower drug release and an overall extended therapeutic effect despite the shorter half-life of LHRH.
• Another example is Risperdal Consta, which improves the effectiveness for patients with schizophrenia while using long-acting PLGA microspheres.

Nanoscale Polymeric Drug Delivery Systems

• Nanoparticles (NPs) facilitate advancements in nanomedicine, enabling targeted therapy.
• PEGylation modifies the NP surface for enhanced in vivo circulation and reduced immunogenicity.
• Targeted drug delivery is key to limiting off-target effects and maximizing treatment efficacy.
• Passive targeting, based on tumor-associated permeability and retention (EPR), and active targeting (ligands on surface of NPs) are specific strategies employed in this field.

Polymer Micelles

• Pluronic (poloxamers) micelles are nonionic triblock copolymers (PEO–PPO–PEO) exhibiting surfactant functionality.
• They encapsulate hydrophobic drugs in their core, creating robust drug delivery vehicles.

Naturally Occurring Biodegradable Polymers

• Materials include proteins (collagen, albumin, gelatin), and polysaccharides (agarose, alginate, carrageenan, hyaluronic acid, chitosan, cyclodextrins).
• These materials, although potentially useful, typically exhibit lower reproducibility and versatility compared to synthetic counterparts.
• Chitosan is often used as a drug delivery matrix, benefiting from an ability to remain in vivo for an extended time and interact with mucin.
• Alginate and hyaluronic acid (HA) also demonstrate diverse applications in tissue engineering and drug delivery due to their biocompatibility.

Chitosan

• Derived from crustacean exoskeletons, chitosan acts as a biodegradable matrix for drug delivery.
• Its deacetylation status influences its crystallinity and degradation rates, impacting in vivo behavior.
• The insolubility of chitosan in water necessitates prior solubilization (with dilute acid) before use.

Hyaluronic Acid (HA)

• HA is a naturally occurring polysaccharide involved in tissue engineering and drug delivery.
• Its hydrophilic nature and high water absorption capacity allow for expansion and potential drug delivery.
• The presence of carboxyl groups leads to its anionic character, crucial for localized targeting.

Alginate

• Derived from brown algae, alginate is a naturally occurring anionic polysaccharide.
• Its variable molecular weight and composition affect its physicochemical properties, including viscosity and water uptake.
• Alginate's potential as a drug delivery system arises from its mucoadhesive character, enabled by the presence of free carboxyl groups interacting with mucin.