You are hereDENDRIMERS FOR NOVEL DRUG DELIVERY: AN OVERVIEW
DENDRIMERS FOR NOVEL DRUG DELIVERY: AN OVERVIEW
Roopesh Sachan*1, Prof. Satyanand Tyagi2, Tarun Parashar1, Soniya1, Patel Chirag J*3,Patel Pinkesh3, Rishikesh Gupta4
1*Department of Pharmaceutics, Himalayan Institute of Pharmacy and Research, Rajawala, Dehradun, Uttarakhand, India-248007.
2President & Founder, Tyagi Pharmacy Association (TPA) & Scientific Writer (Pharmacy), Chattarpur, New Delhi, India-110074.
3Department of Pharmaceutics, Maharishi Arvind Institute of Pharmacy, Mansarovar, Jaipur, Rajasthan, India-302020.
4Institute of Pharmacy, Bundelkhand University, Jhansi, Uttar Pradesh, India-284128.
*firstname.lastname@example.org, +91-9557469989, 9236167104
Nanoparticle drug-delivery systems are the popular ones as are able to increase the selectivity and stability of therapeutic agents. However reticuloendothelial system (RES) uptake, drug leakage, immunogenicity, hemolytic toxicity, cytotoxicity, hydrophobicity restrict the use of these nanostructures. These shortcomings are overcome by surface engineering the dendrimer such as Polyester dendrimer, Citric acid dendrimer, Arginine dendrimer, Glycodendrimers, PEGylated dendrimers, etc.The field of Dendrimers has recently emerged as the most commercially viable technology of this century because of its wide-ranging potential applications in many fields such as: healthcare, electronics, photonics, biotechnology, engineering products, pharmaceuticals, drug delivery, catalysis, electronic devices, environmental issues and nanotechnologies. Dendrimer as a drug delivery agent is a promising, safe and selective drug delivery option.
It’s highly selective nature for targeting the desired tissue is the most essential property and holds a promising future for the treatment of several disorders. Its other properties like very small size, polyvalency, monodispersity, stability make it an appropriate carrier for delivering drugs with precision and selectivity.
Dendrimers are being used as drug delivery systems for various drugs like anticancer drugs (methotrexate), drug for prevention of HIV, enhancing bioavailability of pilocarpine for ocular drug delivery. Dendrimers help in achieving increased bioavailability, sustained, controlled as well as targeted release of drug. There is reduction in the amount of drug and systemic toxicity while the therapeutic efficacy increases. This approach as a drug delivery system certainly promises a reliable, safe, selective and precise method of drug delivery.
Reference Id: PHARMATUTOR-ART-1583
The word “Dendrimer” originated from two words, the Greek word dendron, meaning tree, and meros, meaning part . Dendrimer is a nanoparticle (10-9) and so has advantages over microparticles or others due to its small size, easy uptake by cells (through endocytosis). They are branched macromolecules have a central core unit having a high degree of molecular uniformity, narrow molecular weight, distribution, specific size and shape characteristics, and a highly- functionalized, terminal surface .
Figure 1: Structure of dendrimer
The manufacturing process is a series of repetitive steps generating shells, starting with a central initiator core. Each subsequent shell represents a new "generation" of polymer with a larger molecular diameter, twice the number of reactive surface sites, and approximately double the molecular weight of the preceding generation .
Due to their multivalent and monodisperse character, dendrimers have stimulated wide interest in the field of chemistry and biology, especially in applications like drug delivery, gene therapy and chemotherapy. Dendrimers have cellular uptake through endocytosis and thus brings drug “bound” to dendrimers into the cell .
Figure 2: Dendrimer and Dendron
ADVANTAGES OF DENDRIMERS
1. In target drug delivery: Dendrimers are suitable for targeting solid tumours due to increased permeability, limited drainage in tumour vasculature which will lead to accumulation of macromolecules in tumour (enhanced permeation rate). There is also reduction in amount of drug used via targeted delivery (attaching site specific ligands at surface or magnetic guidance) and thus reduction in systemic toxicity.
2. Drugs can be easily made to remain within layers of skin and not penetrate in systemic circulation.
3. Medication to the affected part inside a patient's body directly.
4. Controlled and sustained release of drugs can be obtained.
5. Bypassing the gastric medium and hence the eschewing the variation due to effect of gastric secretions.
6. Increase in therapeutic efficacy, decrease in side effects: decreased clearance of drug via altered distribution of drug in organs at site of localization and transportation due to controlled and sustained release of the drug.
7. Relatively high drug loading [3, 5].
COMPONENTS OF A DENDRIMER STRUCTURE [1, 3, 6, 7]
1. Generation of Dendrimer
It is the hyperbranching when going from the centre of the dendrimer towards the periphery, resulting in homostructural layers between the focal points (branching points). The number of focal points when going from the core towards the dendrimer surface is the generation number. That is a dendrimer having five focal points when going from the centre to the periphery is denoted as the 5th generation dendrimer. Here, we abbreviate this term to simply a G5-dendrimer, e.g. a 5th generation polypropylene imine is abbreviated to a “G5-PPI-” dendrimer, The core part of the dendrimer is sometimes denoted generation “zero”, or in the terminology presented here “G0”. The core structure thus presents no focal points, as hydrogen substituents are not considered focal points. Intermediates during the dendrimer synthesis are sometimes denoted half-generations; a well-known example is the carboxylic acid-terminated PAMAM dendrimers.
The dendrimer shell is the homo-structural spatial segment between the focal points, the “generation space”. The “outer shell” is the space between the last outer branching point and the surface. The “inner shells” are generally referred to as the dendrimer interior.
In dendrimers, the outer shell consists of a varying number of pincers created by the last focal point before reaching the dendrimer surface.
In PPI and PAMAM dendrimers the number of pincers is half the number of surface groups (because in these dendrimers the chain divides into two chains in each focal point).
It is also generally referred to as the “terminal group” or the “surface group” of the dendrimer. Dendrimers having amine end-groups are termed “amino-terminated dendrimers”.
Figure 3: Three dimensional projection of dendrimer core-shell architecture for G=4.5 PAMAM dendrimer with principal architectural components (I) core, (II) interior & (III) surface
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