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Drug delivery is the method/process of administering a pharmaceuticalÂ compound to achieve aÂ therapeutic effectÂ in humans.Â Most common routes of administration include through the mouth,Â skin, nasal andÂ inhalation routes.Â Many medications such as peptide and protein, antibody, vaccine and geneÂ based drugs, in general may not be delivered using these routes because they might be susceptible to enzymatic degradation or can't be absorbed into the systemic circulation efficiently due to molecular size and charge issues to be therapeutically effective. For this reason many protein and peptideÂ drugs have to be delivered byÂ injectionÂ or aÂ nano-needleÂ array.
Current efforts in the area of drug delivery include the development ofÂ targeted deliveryÂ in which the drug is only active in the target area of the body and sustained release formulationsÂ in which the drug is released over a period of time in a controlled manner from a formulation. In order to achieve efficient targeted delivery, the designed system must avoid the host's defence mechanisms and circulate to its intended site of action.Â Types of sustained release formulations includeÂ liposomes, drug loaded biodegradableÂ microspheresÂ and drug polymer conjugates. Monoclonal antibodies are used in heart disease, multiple sclerosis, disorders of the immunological defence system, and vial/bacterial infections. A number of drug delivery systems are currently under investigation to circumvent the limitation commonly found in conventional dosage forms and improve the potential of the respective drug.
Types of advances:
Liposomes are made up of one phospholipid bilayer (20-100nm), a couple of phospholipid bilayers (100-500nm) or many phospholipid bilayers (<500nm). The centre of the liposomal is polar which enables both lipophilic and hydrophilic drugs to be put in a tablet. Liposomes made with phosphatidylcholine have great compatibility, are easy to prepare, increased solubility of drugs, and improves oral absorption. However they are still unstable in the GI tract. Due to this instability their use is limited as the content may leak out because of poor controlled release and they are hard to store. Therefore, ethanol and surfactants were added to liposomes to create ethosomes and transferosomes which have increased flexibility. These systems are specially designed for skin delivery due to their facilitated fusion and malleability (transferosomes are ultra-deformable) with membranes and have shown that they can be modulated from superficial skin (e.g. treatment of Herpes virus) to full dermal penetration overcoming limitation commonly found in liposomes. The eLiposome is used in cancer therapy by using ultrasound. A number of products created from liposomes are available such as PevarylÂ® containing econazole used to treat dermatomycosis, DiclacÂ® for therapy of osteoarthritis (Nuno Martinho, Christiane Damgé, Catarina Pinto Reis 2011).
Nanoparticles (10-200nm) are in the solid state and are either shapeless or clear. They are able to condense a drug, therefore protecting it against chemical and enzymatic degradation. Nano-capsules are vesicular systems in which the drug is confined to a cavity surrounded by a unique polymer membrane. Nano-spheres are matrix systems in which the drug is physically and uniformly dispersed. Nanoparticles as drug carriers can be formed from both biodegradable polymers and non-biodegradable polymers. 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 per-oral route (Nuno Martinho, Christiane Damgé, Catarina Pinto Reis 2011).
Solid Lipid Nanoparticles (SLN) is made up from lipids, solid at room and body temperature, such as triglycerides. Contrary to liposomes, SLN have shown to be stable for a long period, protect labile compounds from chemical degradation and can be processed up to large-scale production. However, they still present problems related to their loading efficiency due to the formation of a lipid crystal matrix and possible changes of the physical state of the lipids. To overcome this limitation, a novel structure composed of a mixture of lipids solid and fluid at room temperature (semi-liquid formulations) named nanostructured lipid carriers (NLC) were produced. This system shows high encapsulation efficiency and loading capacity due to the formation of less ordered lipid matrix, and they show long term stability with a controlled release and without burst effect (Nuno Martinho, Christiane Damgé, Catarina Pinto Reis 2011).
Application to the skin desires two effects: transdermal and topical effects. The transdermal delivery has gained a significant importance for systemic treatment as it is able to avoid first-pass metabolism and major fluctuations of plasma levels typical of repeated oral administration. SLN, due to an initial burst release followed by water evaporation, proved to penetrate human skin. The rapid degradation of those systems may promote contact with the skin and the occlusion may promote drug uptake. Example, transfersomes with ketoprofen (DiractinÂ®) were applied as a transdermal system in a multicentre, randomized, double-blind trial and showed similar efficacy in relief of knee osteoarthritis compared to celecoxib. In addition, liposomes tend to fuse at the skin surface and marked changes can be induced in the horny layer depending on the phospholipids used as intercellular deposition can occur and destroy lipid membranes. Antifungal drugs are of special interest and although current formulations cure the majority of the problems an econazole liposome formulation in vitro has shown better cure rates. In general, percutaneous drug absorption appears to be increased via association with dendrimers due to their ability to interact with lipid bilayers in the skin. Moreover, targeting specific areas of the skin can be tailored (Tarl W. Prow, Jeffrey E. Grice, Lynlee L. Lin, Rokhaya Faye, Margaret Butler, Wolfgang Becker, Elisabeth M.T. Wurm, Corinne Yoong, Thomas A. Robertson, H. Peter Soyer, Michael S. Roberts 2011).
Were first used in the 1970's and were a form of lactic acid. Polymeric materials are easy to processing. There are two broad categories of polymer systems known as "microspheres" because of their size and shape. One involves the encapsulation of a pharmaceutical product within a polymer shell, and the other describes a system in which a drug is physically entrapped within a polymer network (Bodor, 1996).
The release of medications from either is diffusion-controlled. Modern research is aimed at investigating biodegradable polymer systems. These drug deliverers degrade into biologically acceptable compounds, often through the process of hydrolysis, which subsequently leave their incorporated medications behind. The degradation process itself involves the breakdown of polymers into lactic and glycolic acids. These acids are eventually reduced by the Kreb's cycle to carbon dioxide and water (Bodor, 1996).
Early research into biodegradable systems focused on naturally occurring polymers but has recently moved into the area of chemical synthesis. Specifically, a fast-degrading matrix consists of a hydrophilic, amorphous, low-molecular-weight polymer that contains atoms other than carbon in its backbone and is grown either stepwise or through condensation reactions. Therefore, varying each of these factors allows researchers to adjust the rate of matrix degradation and, subsequently, control the rate of drug delivery (Bodor, 1996).
Dendrimers can be designed to target specific structures. They have a remarkable well-defined control over size with narrow polydispersity. In addition, they have a large surface functionality providing a wide range of applications such as drug and gene delivery, biological adhesives, imaging agents. Thus, they can be used for oral, transdermal, ocular and intravenous deliveries. Moreover, dendrimers have shown that they can easily cross cell barriers by both paracellular and transcellular pathways. Dendrimers can be structurally modified. This modification can be made to the nature of the core and the scaffold giving polyfunction capacity to the dendritic structure. In general, dendrimers are terminated with amine surface groups but can also be terminated with carboxylate. Additionally, dendrimers are non-immunogenic and are small enough to escape the vasculature and target tumor cells. Their size can be tailored to be below the threshold for renal filtration. Dendrimers provide a high loading capacity with controlled release which can be modulated to actively release the agent by pH-triggering cleavage. The rate of drug release from the matrix is influenced by the nature of the linking bond between the drug and scaffold and the targeted physiological domain for intended release. Several dendrimer-based diagnostic and/or in vitro technologies are already in the market such as Stratus CS which is a dendrimer-coupled antibody reagents, Superfect (activated dendrimer technology for DNA transfection into a broad range of cell lines) and PriofectTM which is a transfection reagent. Priostarâ„¢ and STARBURSTÂ® have also been designed to be used as targeted diagnostic and therapeutic delivery systems for a wide variety of drugs to cancer cells and other diseases. As well, VivagelÂ® is a microbicide for prevention of HIV and HSV and it is based on dendrimers (Nuno Martinho, Christiane Damgé, Catarina Pinto Reis 2011).
Products are made fast by nanotechnology. Nano-medicine develops new approaches and therapies using a nanometer. The materials display different physicochemical properties due to their small size, surface structure and high surface area. These properties allow nano-particulate systems to overcome current limitations. Nanotechnology is being used in gene delivery and diagnostics (Nuno Martinho, Christiane Damgé, Catarina Pinto Reis 2011).
Discussion and conclusions:
Nanoparticles are being used as drug delivery systems with great success. They are being used in anti-tumour therapy, gene therapy, and AIDS therapy, radiotherapy, in the delivery of proteins, antibiotics, viro-statics, and vaccines and as vesicles to pass the blood-brain barrier (Costas Kaparissides, Sofia Alexandridou, Katerina Kotti and Sotira Chaitidou 2006).
Nanoparticles provide massive advantages regarding drug targeting, delivery and release; it is one of the major tools in nanomedicine. The main goals are to improve their stability in the biological environment, to mediate the bio-distribution of active compounds, improve drug loading, targeting, transport, release, and interaction with biological barriers. The cytotoxicity of nanoparticles or their degradation products remains a major problem, and improvements in biocompatibility are a main concern of future research (Costas Kaparissides, Sofia Alexandridou, Katerina Kotti and Sotira Chaitidou 2006).
Those carriers provide the hope to treat and diagnose several diseases. Several technologies have advanced into clinical studies and are nowadays market products that have shown results. It was also shown in this review that these recent drug carriers are a promising set of technologies that already penetrated the cancer area and they likely have a strong impact in this field in the future. In fact, the rationale development of anticancer carriers will provide new ways of treatment, circumventing current limitations for conventional dosage forms (Costas Kaparissides, Sofia Alexandridou, Katerina Kotti and Sotira Chaitidou 2006).
There are many technological challenges to be met, in developing the following techniques:
Nano-drug delivery systems that deliver large but highly localized quantities of drugs to specific areas to be released in controlled ways;
Controllable release profiles, especially for sensitive drugs;
Materials for nanoparticles that are biocompatible and biodegradable;
Architectures / structures, such as biomimetic polymers, nanotubes;
Technologies for self-assembly;
Functions (active drug targeting, on-command delivery, intelligent drug release devices/ bioresponsive triggered systems, self-regulated delivery systems, systems interacting with the body, smart delivery);
Virus-like systems for intracellular delivery;
Nanoparticles to improve devices such as implantable devices/nanochips for nanoparticle release, or multi reservoir drug delivery-chips;
Nanoparticles for tissue engineering; e.g. for the delivery of cytokines to control cellular growth and differentiation, and stimulate regeneration; or for coating implants with nanoparticles in biodegradable polymer layers for sustained release;
Advanced polymeric carriers for the delivery of therapeutic peptide/proteins (biopharmaceutics),
And also in the development of:
Combined therapy and medical imaging, for example, nanoparticles for diagnosis and manipulation during surgery (e.g. thermotherapy with magnetic particles);
Universal formulation schemes that can be used as intravenous, intramuscular or peroral drugs
Cell and gene targeting systems.
User-friendly lab-on-a-chip devices for point-of-care and disease prevention and control at home.
Devices for detecting changes in magnetic or physical properties after specific binding of ligands on paramagnetic nanoparticles that can correlate with the amount of ligand.
Better disease markers in terms of sensitivity and specificity (Costas Kaparissides, Sofia Alexandridou, Katerina Kotti and Sotira Chaitidou 2006).