Liposomes

Definition: are the lipid bodies which are in the form of small vesicles of a bilayer of phospholipid encapsulating an aqueous space ranging from about 0.03-10um in diameter.

Introduction: Lipid membrane of a liposome consists of a bilayer forming amphiphile (a chemical compound having both hydrophilic and lipophilic properties) cholesterol and a charge generating molecule.This structure presents an overall hydrophilic membrane like assembly in which the apolar or lipophilic portion of the amphiphilic molecule points inwards while the polar or hydrophilic portion points outward of the lamellar structure. These dosage forms can be administered via parentral, topical and by inhalation routes.

Basic Properties of Liposomes:

  • Their major constituent is the phospholipid molecule. Synthetic or natural phospholipids can be used, phosphatidyl choline being mainly used.
  • In addition to the phosphatidylcholine which possess a neutral charge, liposomes also contain fatty acyl chains of different lengths.
  • The serum-induced instability which occurs when the liposome membrane binds with the serum proteins can be reduced by incorporating cholesterol.
  • Liposomal parentral preparations require more attention towards factors like in vivo profiles and stability during its shelf-life.

Advantages of this novel drug delivery system:

  • Liposomes can be manufactured in a number of sizes, compositions, charge, varying surface morphologies.
  • Are biologically inert, do not elicit their own pharmacological actions and are completely biodegradable.
  • The drugs encapsulated in the liposomes do not get subjected to the enzymatic degradations.
  • Both water soluble as well as water insoluble drugs can be delivered by this kind of dosage form.
  • Antibiotics, enzymes, hormones can be encapsulated and delivered to their sites of action through liposomal drug delivery.
  • They are specifically advantageous for the targeted drug delivery i.e. transporting and localizing the drug on the diseased cell, tissues etc which consequently elevates the drug’s efficacy and reduces its toxicity.
  • Drugs like anti-viral, anti-fungal, anti-bacterial, vaccines, gene therapeutics can be made more safe and active by encapsulating these agents in a liposome.
  • Present applications of liposomes are in immunology, dermatology, vaccine adjuvant, eye-disorders, and brain targeting, infective diseases and in tumor therapy.

Factors affecting the working of Liposomes:

  • Size, charge, degree of surface hydration, route of administration defines the mechanism of distribution and in vivo functioning of the liposomes.
  • After IV administration, the liposomes get taken up by the reticuloendothelial system which eliminates them from the body.
  • Plasma proteins like albumin, lipoproteins, HDL, LDL etc. can also interact and bind to these somes and destabilize them.
  • Protein binding can also trigger an immunological reaction because of the ligands bound to it.
  • In order to prevent liposome’s clearance through RES, liposomes are coated by PEG (polyethylene glycol).
  • Another method is to administer the non-drug containing liposomes to saturate the RES and then administer the active drug containing liposomes.
  • It has also been seen that infections and tumor growth induce inflammation which compromises the vasculature permeability and thus leads to an increased localization and enables more lipososmes to gather at such sites. If this liposomal accumulation is in action then the increased circulation time that results from preventing the first pass effect causes profound and enhanced drug targeting.

How Subcutaneous & Intra-muscular administrations of liposomes work?

  • SC & IM administered liposomes are of larger size and they behave like drug depots by getting trapped at the injection sites.
  • The specificity of the lymph nodes in draining the selected size of particles plays a role in increasing the liposomal localization. As the size limit of particles to be delivered by the lymph nodes is 20-3-nm, liposomes of sizes >40-50nm can easily retain in the lymph nodes on entering the lymphatic system.

 

Changes in the Pharmacokinetics of a drug:

  • On comparing the drug encapsulated in the liposome to the same drug in aqueous solution, revealed a high degree of difference in the absorption, distribution & clearance which ultimately changes the efficacy and toxic profiles of the drug.
  • PEGylated liposomes can increase the circulation time by decreasing the size and by modifying the surfaces and can enhance the stability of the drug and aids it in surpassing the RES clearance, therefore, providing lesser toxicity and extended plasma drug levels.
  • Even though only some portion of liposome may accumulate at the target site at one time, the longer it circulates, the more it can concentrate at the targeted tissue.

Oral delivery of Liposomes:

  • The oral delivery of the liposomes is being studied a lot now.
  • The limitations to its delivery through oral route are the pH of the GIT, bile salts, pancreatic enzymes, all of which can cause denaturation of the liposome.
  • But the use of micro-emulsions can prove beneficial in this case. The micro-emulsions enclosed in the soft gel capsules have shown to increase the bioavailability of the drug.

 Conclusion: Liposomes are the potential drug delivery systems. Moving from the first generation or conventional vesicles, research is now being done on longer circulating second generation liposomes.

Reference:

  • Remington the Science and Practice of Pharmacy.
  • Journal of Pharmaceutical Sciences.
Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s