Novel Drug Delivery Systems--

Novel Drug Delivery Systems--

A Presentation by Ms.Satya Vadlamani , CMD Murli Krishna Pharma Pvt.Ltd.

Novel Drug Delivery Systems—Nano Spheres

The method by which a drug is delivered can have a significant effect on its efficacy. Some drugs have an optimum concentration range within which maximum benefit is derived, and concentrations above or below this range can be toxic or produce no therapeutic benefit at all. On the other hand, the very slow progress in the efficacy of the treatment of severe diseases, has suggested a growing need for a multidisciplinary approach to the delivery of therapeutics to targets in tissues. From this, new ideas on controlling the pharmacokinetics, pharmacodynamics, non-specific toxicity, immunogenicity, bio-recognition, and efficacy of drugs were generated. These new strategies, often called Novel Drug Delivery Systems (NDDS), are based on interdisciplinary approaches that combine polymer science, pharmaceutics, bio-conjugate chemistry, and molecular biology. Dramatic changes have been introduced, with new technology and new devices now on market.

In some cases traditional capsules and ointments have been replaced by osmotic pumps, wearable ambulatory pumps, electrically assisted drug delivery and host of other delivery methods based on various polymer technologies. In some cases the new drugs require new delivery systems because the traditional systems are inefficient and ineffective. Some therapies may become very site specific and require very high concentrations of drugs in selected sites of body, as more controlled drug delivery systems will be available very near future. New drug delivery system development is largely based on promoting the therapeutic effects of a drug and minimizing its toxic effects by increasing the amount and persistence of a drug in the vicinity of target cell and reducing the drug exposure of non-target cells1,2,3&4. 

Novel drug delivery systems can include those based on physical mechanisms and those based on biochemical mechanisms. Physical mechanisms also referred as controlled drug delivery systems include osmosis, diffusion, erosion, dissolution and electro transport. Biochemical mechanisms include monoclonal antibodies, gene therapy, and vector systems, polymer drug adducts and liposomes. Therapeutic benefits of some new drug delivery systems include optimization of duration of action of drug, decreasing dosage frequency, controlling the site of release and maintaining constant drug levels12,13&14. 

Among drug carriers one can name soluble polymers, micro particles made of insoluble or biodegradable natural and synthetic polymers, microcapsules, cells, cell ghosts, lipoproteins, liposomes, and micelles. The carriers can be made slowly degradable, stimuli-reactive (e.g., pH- or temperature-sensitive), and even targeted (e.g., by conjugating them with specific antibodies against certain characteristic components of the area of interest).

Targeting is the ability to direct the drug-loaded system to the site of interest. Two major mechanisms can be distinguished for addressing the desired sites for drug release: (i) Passive and (ii) Active targeting. Drug Delivery Carriers Colloidal drug carrier systems such as micellar solutions, vesicle and liquid crystal dispersions, as well as nanoparticle dispersions consisting of small particles of 10–400 nm diameter show great promise as drug delivery systems. When developing these formulations, the goal is to obtain systems with optimized drug loading and release properties, long shelf-life and low toxicity. The incorporated drug participates in the microstructure of the system, and may even influence it due to molecular interactions, especially if the drug possesses amphiphilic and/or mesogenic properties19&20. Liposomes Tiny pouches made of lipids, or fat molecules surrounding a water core widely used for clinical cancer treatment. Several different kinds of liposomes are widely employed against infectious diseases and can deliver certain vaccines.

During cancer treatment they encapsulate drugs, shielding healthy cells from their toxicity, and prevent their concentration in vulnerable tissues such as those of patient kidneys and liver. Liposomes can also reduce or eliminate certain common side effects of cancer treatment such as nausea and hair loss. They are form of vesicles that consist either of many, few or just one phospholipid bilayers. The polar character of liposomal core enables polar drug molecules to be encapsulated. Amphiphilic and lipophilic molecules are solubilized within phospholipid bilayer according to their affinity towards phospholipids. 

Hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids. The networks are composed of photopolymers or copolymers, and are insoluble due to the presence of chemical crosslinks (tie-points, junctions), or physical crosslinks, such as entanglements or crystallites. Hydrogels exhibit a thermodynamic compatibility with water, which allows them to swell in aqueous media. They are used to regulate drug release in reservoir-based, controlled release systems or as carriers in swellable and swelling-controlled release devices. On the forefront of controlled drug delivery, hydrogels as enviro-intelligent and stimuli-sensitive gel systems modulate release in response to pH, temperature, ionic strength, electric field, or specific analyte concentration differences. In these systems, release can be designed to occur within specific areas of the body (e.g., within a certain pH of the digestive tract) or also via specific sites (adhesive or cell-receptor specific gels via tethered chains from the hydrogel surface). Hydrogels as drug delivery systems can be very promising materials if combined with the technique of molecular imprinting.

 Nanoparticles (including nanospheres and nanocapsules of size 10-200 nm) are in the solid state and are either amorphous or crystalline. They are able to adsorb and/or encapsulate a drug, thus protecting it against chemical and enzymatic degradation. In recent years, biodegradable polymeric nanoparticles have attracted considerable attention as potential drug delivery devices in view of their applications in the controlled release of drugs, in targeting particular organs / tissues, as carriers of DNA in gene therapy, and in their ability to deliver proteins, peptides and genes through the peroral route. 

Classification of nanomaterial’s ,  Nanotubes They are hollow cylinders made of carbon atoms. They can also be filled and sealed, forming test tubes or potential drug delivery devices. Nano wires Glowing silica nano wire is wrapped around a single strand of human hair. It looks delicate. It is about five times smaller than virus applications for Nano wires include the early sensing of breast and ovarian malignancies. Nano cantilever. The honey comb mesh behind this tiny carbon cantilever is surface of fly’s eye. Cantilevers are beams anchored at only one end. In Nano world, they function as sensors ideal for detecting the presence of extremely small molecules in biological fluids.

Nanoshells are hollow silica spheres covered with gold. Scientists can attach antibodies to their surfaces, enabling the shells to target certain shells such as cancer cells. Nano shells one day also are filled with drug containing polymers. Quantum dots Quantum dots are miniscule semiconductor particles that can serve as sign posts of certain types of cells or molecules in the body. They can do this because they emit different wavelengths of radiations depending upon the type of cadmium used in their cores. Cadmium sulfide for ultra violet to blue, cadmium selinide for most of the visible spectrum and cadmium telluride for far – infra red and near infra-red. Nano pores Nano pores have cancer research and treatment applications. Engineered into particles, they are holes that are so tiny that DNA molecules can pass through them one strand at a time, allowing for highly precise and efficient DNA sequencing. 

By engineering Nano pores into surface of drug capsule that are only slightly larger than medicines molecular structure, drug manufacturers can also use Nano pores to control rate of drug’s diffusion in body. Gold Nanoparticles These nanoparticles, seen in transmission electron micrograph image, they have solid core. Researchers at north western university are using gold particles to develop ultra-sensitive detection systems for DNA and protein markers associated with many forms of cancer, including breast prostate cancer.

Bucky ball is common name for a molecule called buckminsterfullerene, which is made of 60 carbon atoms formed in shape of hollow ball, discovered in 1985. Bucky balls and other fullerenes because of their chemistry and their unusual hollow, cage like shape extremely stable and can withstand high temperatures.  Applications Bucky balls may see widespread use in future products and applications, from drug delivery vehicles for cancer therapy to ultra-hard coating and military armor. Bucky ball – antibody combination delivers antitumor drugs. Bucky balls to fight allergy. v Bucky balls as powerful antioxidant and also inhibitor of HIV. Demerits v Bucky balls hurt cells. v Bucky balls have high potential to accumulate in living tissue. v Difficulty of targeting drug delivery location24,25,26,27,28&29. Carbon nanotubes Carbon nanotubes can be modified to circulate well within the body. Such modifications can be accomplished with covalent or non – covalent bonding. Modifications can increase or decrease circulation time with in the body. Carbon nanotubes show no significant toxicity when they have modified so as to be soluble in aqueous, body type fluids. They enter readily into the cells. Cancer cells in tumors are larger than normal cells and also exhibit leakage. Large molecules which circulate slowly can leak into and accumulate in cancer cells. Carbon nanotubes carrying active agents have been demonstrated in animal studies to do this. Researchers have also used carbon tubes to deliver the precursors of active drug, which they call a pro drug, eg : Cisplatin  

Dendrimers are precisely defined, synthetic nanoparticles that are approximately 5–10 nm in diameter. They are made up of layers of polymer surrounding a control core. The dendrimers surface contains many different sites to which drugs may be attach and also attachment sites for materials such as PEG which can be used to modified the way of dendrimer which interacts with body. PEG can be attached to dendrimer to ‘disguise’ it and prevent the body’s defense mechanism for detecting it, there by slowing the process of break down. This fascinating particle holds significant promise for cancer treatment. Between capillary blood and alveolar air (air-blood barrier). Transdermal drug delivery avoids problems such as gastrointestinal irritation, metabolism, variations in delivery rates and interference due to the presence of food. It is also suitable for unconscious patients. The technique is generally non-invasive and aesthetically acceptable, and can be used to provide local delivery over several days. Limitations include slow penetration rates, lack of dosage flexibility and / or precision, and a restriction to relatively low dosage drugs. 

Parenteral routes (intravenous, intramuscular, subcutaneous) are very important. The only Nano systems presently in the market (liposomes) are administered intravenously. Nano scale drug carriers have a great potential for improving the delivery of drugs through nasal and sublingual routes, both of which avoid first-pass metabolism; and for difficult-access ocular, brain and intra-articular cavities.