Drug Delivery Using Polymer as Nanoparticle



The fast growing and efficient sector in Biotechnology is Nanotechnology. Nanotechnology has its vast applications and nanomedicine is one among those promising and fruitful applications. Nanomedicine is the medical use of molecular sized particles to deliver drugs, heat, light or any other substances to specific cells in human body. Engineering particles to be used in this way allows detection and treatment of diseases or injuries within targeted cells, thereby minimizing damage to healthy cells in our body. The major task in this process is the drug delivery.

Drug delivery refers to the transport of drug to the site of action. The pharmaceutical formulation containing the active agent may target the molecule for transdermal, oral, or nasal/pulmonary delivery. The overall drug consumption and side effects can be lowered significantly by depositing the active agents in the required cells alone and in only a limited dosage. This highly selective approach reduces costs and human sufferings. An example can be seen in dendrimers and nanoporous materials. They could hold small drug molecules transporting them to desired location. Another method is based on the small electrochemical systems called NEMS (nano electro mechanical system) are being investigated for the active release of drugs. Some potentially important applications include cancer treatment with iron nanoparticles or gold shells. A targeted or personalized medicine reduces the drug consumption and treatment expenses resulting in an overall societal benefit by reducing the costs to public health systems.

Polymer Based Drug Delivery

Conventional drug administration methods entail periodic dosing of a therapeutic agent in a formulation that ensures drug stability, activity, and bioavailability. These methods of administration include parenteral delivery such as by injection, topical delivery using salves or ointments for skin applications or via liquid drops for eye and ear applications, and oral delivery by ingestion, for example of pills, tablets or liquids. Administration of these drug dosage forms results typically in a sharp initial increase in drug concentration, followed by a steady decline in concentration as the drug is cleared and/or metabolized. Repeated administration is necessary, to reach and maintain the drug concentration within the appropriate efficacy range. The result of this periodic drug delivery is a drug concentration profile that oscillates over time.

For drugs that are unstable in the blood stream or gastrointestinal tract, are toxic at high doses or have a narrow therapeutically effective concentration range (therapeutic window), conventional drug delivery methods are inappropriate. Recently developed protein drugs, for example, present unique challenges for drug delivery. Because of their protein nature, oral administration results in protein digestion or hydrolysis in the gastrointestinal tract. Proteins also have very short pharmacokinetic half-lives in the blood stream, being quickly metabolized and cleared, which renders parenteral administration inappropriate. Also, because of their size, proteins are poorly absorbed through the skin and so cannot readily be delivered by topical administration.

Polylactic Acid

Polylactic acid or polylactide (PLA) is a biodegradable, thermoplastic, aliphatic polyester derived from renewable resources, such as corn starch or sugarcanes. Although PLA has been known for more than a century, it has only been of commercial interest in recent years, in light of its biodegradability. Bacterial fermentation is used to produce lactic acid from corn starch or cane sugar. However, lactic acid cannot be directly polymerized to a useful product, because each polymerization reaction generates one molecule of water, the presence of which degrades the forming polymer chain to the point that only very low molecular weights are observed. Instead, lactic acid is oligomerized and then catalytically dimerized to make the cyclic lactide monomer. Although dimerization also generates water, it can be separated prior to polymerization. PLA of high molecular weight is produced from the lactide monomer by ring-opening polymerization using most commonly a stannous octoate catalyst, but for laboratory demonstrations tin(II) chloride is often employed. This mechanism does not generate additional water, and hence, a wide range of molecular weights are accessible.


1. To extract vitamin E from a plant source.

2. To synthesis polylactic acid by microwave method.

3. To prove that microwave method was more efficient than other thermal methods.

4. To synthesis Vitamin E entrapped nanoparticles to be used as a nanocarrier.

5. To study the properties of the grafted copolymer as carrier for drug delivery.

Synthesis Of Nanoparticles With Entrapped Vitamin E

Encapsulation of alpha-tocopherol in polymeric nanoparticles can be achieved by a number of methods, including emulsion or micro emulsion polymerization, interfacial or precipitation polymerization, emulsion evaporation, emulsion diffusion, solvent displacement and salting out. Many studies reported the use of emulsion evaporation method for nanoparticle preparation and entrapment of various drugs.

Biodegradable poly (lactic acid)-grafted amylose was synthesized using a trimethylsilyl (TMS) protection method. Tetrahydrofuran soluble, mostly trimethylsilyl protected amylose was prepared and reacted with potassium tert-butoxide to give the corresponding alkoxide. Poly (lactic acid)-grafted amyloses were obtained by ring-opening anionic polymerization of lactide using the polymeric alkoxides as initiators and subsequent removal of the TMS groups. The obtained graft copolymers show biodegradability and a micro-phase-separated morphology. (Ohya Y et al.1998) To covalently immobilize gelatin or collagen type I on poly-L -lactic acid (PLLA) film surfaces poly(hydroxyethyl methacrylate) (PHEMA) or poly(methacrylic acid) (PMAA) was grafted via photo oxidization and subsequent UV- induced polymerization . For films grafted with PHEMA, methyl sulfonyl chloride was used to activate the hydroxyl groups and for films grafted with PMAA 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide was used to activate the carboxyl groups.

Gelatin and collagen were finally reacted with the activated hydroxyl or carboxyl groups to obtain covalently immobilized protein layers. Grafting of PHEMA, PMAA and protein on the surfaces was confirmed using ATR-IR and XPS. Surface wettability of the modified films was improved. The protein immobilized PLLA may be widely used as a biocompatible material. (Zuwei Ma et al. 2002). A novel copolymer, poly(lactide)-vitamin E TPGS (PLA-TPGS), was synthesized from lactide and d-alpha-tocopheryl polyethylene glycol 1000 succinate by bulk polymerization for nanoparticle formulation of anticancer drugs. 1H NMR, FTIR and GPC were used to detect molecular structure of the copolymer. Paclitaxel-loaded PLA-TPGS nanoparticles were fabricated by a modified solvent extraction/evaporation technique with or without emulsifier involved, which were characterized by laser light scattering for size and size distribution; field emission scanning electron microscopy for surface morphology; zeta potential for surface charge; X-ray photoelectron spectroscopy for surface chemistry. The drug encapsulation efficiency and the in-vitro drug release kinetics were measured by high-performance liquid chromatography.

Drug Delivery

A biologically active conjugate is disclosed comprising a biopolymer and a therapeutic agent joined by a disulfide bond. The conjugate, when formulated in a pharmaceutical composition with a suitable carrier, has improved in-vivo stability and activity, and can be targeted to a variety of cells, tissues and organs.

A new route has been exploited for delivery using micro particles composed of d-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a matrix material blended with poly (caprolactone) for nasal immunization with diphtheria toxoid. Particles were prepared by a double emulsion method, followed by spray drying and the effect of TPGS on size, zeta potential, loading and release of antigen was assessed. Particles composed of TPGS–PCL blends were spherical, smooth and monodisperse, displaying increasing yields after spray drying with increasing concentrations of TPGS. The immune response to diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was shown to be higher than that achieved using PCL microspheres alone. We conclude that TPGS shows significant potential as a novel adjuvant either alone or in combination with an appropriate delivery system.

A biologically based drug delivery vehicle was designed for intra-articular drug delivery using elastin-like polypeptides (ELPs), a biopolymer composed of repeating pentapeptides that undergo a phase transition to form aggregates above their transition temperature. The ELP drug delivery vehicle was designed to aggregate upon intra-articular injection at 37 degrees C and form a drug 'depot' that could slowly disaggregate and be cleared from the joint space over time. We evaluated the in-vivo bio-distribution and joint half-life of radiolabeled ELPs, with and without the ability to aggregate, at physiological temperatures encountered after intra-articular injection in a rat knee. Biodistribution studies revealed that the aggregating ELP had a 25-fold longer half-life in the injected joint than a similar molecular weight protein that remained soluble and did not aggregate. These results suggest that the intra-articular joint delivery of ELP-based fusion proteins may be a viable strategy for the prolonged release of disease-modifying protein drugs for osteoarthritis and other arthritides.


Polylactic acid was prepared by microwave method and the results indicated that more amount of polylactic acid was extracted in less time and hence is more efficient than other thermal methods. Encapsulation of vitamin E in the PLA matrix was suitable technique for synthesis of spherical PLA nanoparticles as the TEM results have clearly shown that this method produced nanoparticles of size less than 100 nm. This method also provided good size distribution. PLA is a hydrophobic polymer. As it cannot take protein and peptide drugs, we have changed its physicochemical properties by grafting it with vitamin E. Higher concentration of PVA provided more drug loading efficiency and good size distribution.The test for compatibility in blood cells portrays that Vitamin E is compatible in blood.






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