Shruti Bhat PhD, MBA, Operations Excellence Expert
  • Home
  • About Shruti
  • Books
  • Insights
  • Operational Excellence
  • Research
    • Innovation Management
    • Leading Research and Development
    • Developer's Diary
  • Case Studies
  • Tools
    • Whitepapers
    • Articles >
      • Business Transformation
      • Process Improvement
      • Business Continuity
      • Change Management
      • Digital Transformation
      • Quality Improvement
    • Checklists and Templates
    • Free eBook
    • Videos
  • Blog
  • Engage Shruti
    • Consulting >
      • Operational Excellence Consulting
      • Business Transformation Consulting
      • Innovation Management Consulting
    • Workshops
  • Contact

Factors governing drug targeting

5/18/2009

0 Comments

 
Various biological processes and events govern drug targeting.  They are as follows:

A. Cellular Uptake and Processing:

Following administration, a drug frequently passes through various cells, membranes and organs to reach its target sites.  These pathways offer opportunities for cell selection and access by targeted drug delivery.

Low-molecular-weight drugs can enter into, or pass through, various cells by simple diffusion processes.  Targeted drug delivery systems often comprise macromolecular assemblies, and are unable to enter into cells by such simple processes.  Instead, they are captured by a process called endocytosis.  Endocytosis is defined as a phenomenon that involves internalization of the plasma membrane, with concomitant engulfment of the extra cellular material (particulate or fluid).  This process can be constitutive or nonconstitutive.  Other methods of gaining access to cells include passive diffusion, membrane fusion, and binding to either specific or nonspecific regions of the cell.

Endocytosis is divided into two types:  phagocytosis and pinocytosis.  The former refers to the capture of particulate matter, whereas the latter represents engulfment of fluids.  Phagocytosis is carried out by specialized cells of the mononuclear phagocyte system (MPS), called phagocytes.  It is mediated by the absorption of specific blood components [e.g. immunoglobulin (Ig) G, complement C3b, and fibronectin], called opsonins, and relevant receptors located on macrophages.  The extent to which a drug is opsonized, and by what plasma protein depends on the size and surface characteristics of the particles.  This, in turn, determines the engulfment mechanism.  

Following ingestion, the phagocytic vacuole (or phagosome) fuses with one or more lyososomes to form phagolysosomes (or secondary lyososomes);  It is here that the digestion of particles by lyososomes acid hydrolases (e.g. protemases, glycosidases, nucleases, phospholipases, phosphatases, and sulfatases) occurs, making the drug available to exert its therapeutic effect.  The internal pH of lysozomes is between 4.5 and 5.5.

Unlike phagocytosis, which is mediated by the serum opsonin, pinocytosis does not require any external stimulus.  Pinocytosis is divided into two types; fluid phase pinocytosis and adsorptive pinocytosis.  Fluid-phase pinocytosis is a nonspecific, continuous process, and is a general process for transporting macromolecular constructs through epithelia, some endothelia, and into various blood cells.  Adsorptive pinocytosis, in contrast, refers to internalization of macromolecules that bind to the cell surface membrane.  If the macromolecule adheres to a general cell surface site, then uptake is referred to as simply nonspecific pinocytosis.  However, if it binds to a specific cell receptor site, then the process is called receptor-mediated pinocytosis.

Once internalized the pinocytosis vesicles interact among themselves or with vesicles of other intracellular origins such as endosomes and lysozomes.

B.  Transport across the epithelial barrier:

The oral, buccal, nasal, vaginal and rectal cavities are all internally lined with one or more layer of epithelial cells.  The transport of macromolecules across the intestinal epithelium may occur by cellular vesicular process by either fluid-phase pinocytosis or specialized (receptor-mediated) endocytotic process.

C.  Extravasation :

Many diseases are known that result from the dysfunction of cells located outside the cardiovascular system.  Thus, for a drug to exert its therapeutic effects, it must egress from the central circulation and interact with its extravascular-extracellular or extravascular-intracellular target(s).  This process of transvascular exchange is called extravasation, and it is governed by the permeability of blood capillary walls.  The main biological features that control permeability of capillaries include the structure of the capillary wall, under normal and (patho) physiological conditions, and the rate of blood and lymph supply.  Physicochemical factors that are of prohydrophilic-lipophilic balance (HLB) characteristics.

D.  Lymphatic Uptake:

Following extravasation, the drug molecules can either reabsorb into the blood stream directly by the enlarged postcapillary interendothelial cell pores found in most tissues or enter into the lymphatic system and then return with the lymph to the blood circulation.
Follow Shruti on Twitter, Facebook, YouTube, LinkedIn
0 Comments

Your comment will be posted after it is approved.


Leave a Reply.

    Shruti Bhat, global leader in business turnaround, operational excellence and continuous improvement
    To contact Dr. Shruti Bhat text or WhatsApp at 1.403.969.6219

    New Book Released!

    Revolutionizing Industries with Lean Six Sigma

    Shruti's YouTube Channel ...

    Picture

    Blog Categories

    All
    3D Printing
    Agile
    Artificial Intelligence
    Automation
    Biotechnology
    Books
    Business Continuity
    Business Turnaround
    Case Studies
    Change Management
    Checklists
    Chemical Industry
    Continuous Improvement
    Design Thinking
    Digitalization
    Drug Delivery
    External News Links
    Hall Of Fame
    Healthcare
    Hoshin Kanri
    HR Development
    Innovation
    Insights
    ISO
    Just In Time
    Kaizen
    Leadership
    LEAN
    Lean Six Sigma
    Life Sciences
    Machine Learning
    Manufacturing
    Medical Devices
    Mistake Proofing
    Motivational Cards
    MSMEs
    Nanotechnology
    Operational Excellence
    Packaging
    Patents
    Personal Products
    Process Improvement
    Product Development
    Productivity Increase
    QbD
    Quality Management
    R&D Leadership
    Robotics
    Service Industry
    Six Sigma
    Strategy
    Supply Chain Logistics
    Telecom Industry
    Templates
    TQM
    Videos
    Voice Of Customer
    Whitepaper
    Workshops

    Shruti's books...

    Picture
    top ten strategic decision-making tools for operational excellence
    shruti bhat, business process management, continuous improvement
    kaizen for pharmaceutcials, medical devices and biotech industry book by Dr Shruti Bhat
    Book on Continuous improvement tools by Dr Shruti Bhat
    kaizen for leaders, continuous process improvement tool to increase profit and organizational excellence by shruti bhat
    kaizen, shruti bhat, continuous improvement, quality, operations management
    how to lead a successful business transformation
    leading organizations through crisis
    emotional intelligence
    how to overcome challenges of creating effective teams
    modular kaizen Vs Blitz kaizen
    How to increase employee engagement as a new boss

Connect with Dr. Shruti Bhat at- ​Twitter, YouTube, LinkedIn​

© Copyright 1992- 2025 Dr. Shruti Bhat ALL RIGHTS RESERVED.
See Terms and Conditions for details on this site usage.
Subscribe to Operational Excellence Academy YouTube Channel
​Subscribe to Operational Excellence Academy YouTube Channel
SHRUTI BHAT, CONTACT
Click to connect.
Created by Macro2Micro Media