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Permeation through skin

Permeation through the skin involves the drug passing through various layers:

1.     Stratum Corneum: The outermost layer, composed of dead keratinized cells, acts as the primary barrier.

2.     Epidermis: Below the stratum corneum, containing living cells and blood vessels.

3.     Dermis: The deeper layer housing nerves, glands, and connective tissue.

4.     Subcutaneous Tissue: The innermost layer with fat and connective tissue.

Permeation through skin
Permeation through skin
  • For effective permeation, drugs must navigate these layers, primarily traversing the stratum corneum via intercellular (between cells), intracellular (through cells), or transappendageal (through hair follicles and sweat glands) pathways.

Permeation through skin

Anatomy of the Skin (Permeation through skin)

  • The skin, the body’s largest organ, performs vital functions such as protection, sensation, temperature regulation, and vitamin D synthesis.

  • It consists of three main layers:

Anatomy of the Skin
Anatomy of the Skin

Epidermis

  • Function: Protection

Sub-layers:
  • Stratum Corneum: Outermost layer of dead, keratin-filled cells; primary barrier to drug permeation.

  • Stratum Lucidum: Thin layer found only in palms and soles.

  • Stratum Granulosum: Produces keratin for skin strength.

  • Stratum Spinosum: Contains immune cells to fight infections.

  • Stratum Basale: Site of new skin cell formation and melanin production.

Dermis

  • Function: Structural integrity

Components:
  • Collagen and elastin fibers for strength and elasticity

  • Blood and lymph vessels for nourishment and immune responses

  • Nerve endings for sensation

  • Sweat and sebaceous glands for temperature regulation and skin hydration

  • Hair follicles.

Hypodermis (Subcutaneous Layer)

  • Note: Not technically part of the skin

Components:
  • Adipose tissue for insulation and cushioning

  • Larger blood vessels

  • Connective tissues.

Accessory Structures

  • Hair: Protection, sensory input, thermoregulation

  • Nails: Protect fingertips and aid in manipulation

  • Sweat Glands: Eccrine (cooling) and apocrine (thicker sweat)

  • Sebaceous Glands: Produce sebum to moisturize skin and hair

Specialized Cells

  • Keratinocytes: Produce keratin

  • Melanocytes: Produce melanin for UV protection

  • Merkel Cells: Light touch sensation

  • Mast Cells: Involved in inflammation

  • Lymphatic Vessels: Aid immune responses

Functions of the Skin

  1. Protection: Against mechanical impact, pathogens, UV radiation

  2. Sensation: Detects temperature, touch, vibration, pain

  3. Thermoregulation: Through sweat and blood vessel adjustments

  4. Metabolic Functions: Vitamin D synthesis

  5. Immune Defense: Detects and fights pathogens

Mechanism of Drug Transport Across the Skin

Mechanism of Drug Transport Across the Skin
Mechanism of Drug Transport Across the Skin

Primary Mechanisms

Passive Diffusion

  • Movement from high to low concentration

  • No energy required

Active Transport

  • Uses carrier proteins or pumps

  • Requires energy

Electrophoresis and Iontophoresis

  • Utilize electrical currents to move charged molecules

Layers Involved

  1. Stratum Corneum: Main barrier; drugs must penetrate this layer first

  2. Epidermis (Excluding Stratum Corneum): Continuation of diffusion

  3. Dermis: Absorption into systemic circulation

Factors Affecting Permeation

  • Molecular Size: Smaller molecules penetrate more easily

  • Lipophilicity: Lipophilic drugs permeate better through lipid-rich layers

  • Permeation Enhancers: Chemicals that disrupt the stratum corneum to facilitate drug passage.

Routes of Skin Penetration

Routes of Skin Penetration

Transcellular Route

  • Through cells of the stratum corneum and epidermis

  • Challenging due to hydrophobic barriers

Intercellular Route

  • Between the cells through lipid-rich domains.

  • Favored by lipophilic drugs but hindered by the tortuous path

Transappendageal (Shunt) Route

  • Through hair follicles, sweat, and sebaceous glands

  • Useful for certain drugs, especially macromolecules

Subcutaneous Route

  • Direct delivery into subcutaneous tissue via injections

  • Bypasses skin barriers, not typically used in TDDS


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