>Drug Delivery System

5.Drug Delivery System:
(From Wikipedia, the free encyclopedia)
Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals[1] [2]. Drug Delivery technologies are patent protected formulation technologies that modifies drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy & safety and patient convenience & compliance[3]. Most common methods of delivery include the preferred non-invasive peroral (through the mouth), topical (skin), transmucosal (nasal, buccal/sublingual, vaginal, ocular and rectal) and inhalation routes [4][5]. Many medications such as peptide and protein, antibody, vaccine and gene based drugs, in general may not be delivered using these routes because they might be susceptible to enzymatic degradation or can not be absorbed into the systemic circulation efficiently due to molecular size and charge issues to be therapeutically effective. For this reason many protein and peptide drugs have to be delivered by injection. For example, many immunizations are based on the delivery of protein drugs and are often done by injection.
Current efforts in the area of drug delivery include the development of targeted delivery in which the drug is only active in the target area of the body (for example, in cancerous tissues) and sustained release formulations in which the drug is released over a period of time in a controlled manner from a formulation.

Drug Delivery Market :

The global drug delivery market earned $426.9 billion in 2005,a considerably larger industry than biomedical devices! However, the oral delivery sector alone accounts for $283.7 billion,which assists in putting in perspective the potential contribution of medical devices in this market. Drug delivery systems are conduits by which therapeutic agents are introduced to the body with the intention of interacting at a target site of action. New drug delivery strategies have successfully improved patients’ lives through providing convenience (transdermal patches, insulin pumps), more tolerable administration options (inhalation devices, implants), and improved efficacy for conventional therapies and procedures
(drug-eluting stents, liposomes). Future breakthroughs in delivery could include long-term, autonomous devices, and next-generation localizing and targeting of chemotherapeutics.

Small-scale, in vivo drug delivery systems require the coupling of innovative device technology and advanced therapeutic agents. A compromise between device size and therapeutic payload must be optimized to avoid developing an ineffective delivery system that is too small and incapable of delivering the desired medications at the required doses of micro-liters or more. Reformulations of conventional therapeutics to produce higher potency drugs would assist maintaining the small scale of the devices; however, additional requirements such as improved stability and solubility may also present limitations to shelf life and deliverability. I have much confidence that the pharmaceutical industry will embrace efforts to meet the demands of future drug delivery technologies based on two motivations:
(1) new and effective drug delivery modalities may increase therapeutic efficacy and reduce harmful side effects and, from a more pragmatic point of view,
2) “Big Pharma” is scrambling to find ways to prevent the demise of their blockbuster drugs through patent expiration.
New drug delivery systems may provide “line extension” life preservers to the pharmaceutical industry which is expected to lose $80 billion to expiring patents in the next few years! Either way, it may be a win-win situation for patients since the future may hold both new innovative drug delivery systems and cheaper generic drugs; Big Pharma will not be able to save them all! Disregarding the economic impact of new drug delivery systems, the future  clinical prospects for delivery devices is truly exciting, especially if the integration of advanced electronics and sensors validate modulated, remotecontrolled, and autonomous systems. The utility of such devices could be easily applied to civilian life, third world countries, the battlefield, and even the moon! Constant or modulated release may provide convenience for hormonal  therapies such as leuprolide acetate, which is conventionally administered on a monthly basis for advanced prostate or ovarian cancer patients.

The same release strategies would be critical for third world countries where health care resources are poorly accessible; the delivery of interferon alpha to hepatitis C patients is a perfect example since conventional treatments require daily injections, or at least three times a week, for a 16-week period. For such cases, these treatment regimes are not practical and require alternative discourse.

Remote activation of morphine administration for soldiers wounded on the battlefield is a relevant application; this approach allows medics to remotely activate pain relief instantly and potentially from a safe distance if needed,and reduces opportunities for abuse. Missions to the moon and Mars may be
perceived as outlandish and costly ventures; however, the enabling technology that will make these travels possible will have direct application to civilian life.

Remote-controlled or autonomous drug delivery devices will allow scientists to essentially bring the hospital to the astronauts, where hospitals are not available.Autonomous delivery or the release of drugs, as the direct response to a physiologic change, has unlimited application potential for diseases that involve chemical imbalances.

An additional endeavor of future drug delivery devices is to target therapeutics to the site of disease, for example a cancer lesion. In principal, this can be achieved through a variety of strategies, such as physical, biological, or molecular targeting of pathologically relevant sites with a desired hemotherapeutic
agent. Such targeting mechanisms are already employed in the clinic and are commercially available. However, no level of targeting sophistication will produce substantial benefits in the therapeutic index unless the agents of therapeutic action can reach the intended lesion sites at the right dose; which explains the reasoning why current treatment strategies have not been totally revolutionized
by the advent of today’s emerging targeted therapies.

The challenge to drug delivery is to overcome the deficiencies of typical therapeutic strategies. Conventional cancer chemotherapeutics gain access to the blood stream through intravenous (I.V.) administration and are required to penetrate the extravascular space and present at the tumor lesion at an adequate concentration such to inflict lethal toxicity. Unfortunately, only 1 out of 100,000
molecules of the drug successfully reaches the intended site,permitting the overwhelming majority of the highly toxic, nondiscriminating, systemically disbursed, poison to manifest in a number of cruel side effects associated with cancer chemotherapy. Unfortunately, intrinsic to the body defense system are
several extremely effective obstacles (collectively termed  biobarriers ) that largely  prevent injected chemicals, biomolecules, nanoparticles, and any other foreign agents of therapeutic action from reaching their intended destinations.

Biobarriers are sequential in nature, and therefore the probability of reaching the therapeutic objective is the product of the individual probabilities of overcoming each one of them.

A corollary is that any efficient delivery method must be provided with tools that allow it to overcome all of these barriers, because opening all of the doors is necessary, but opening only one along a single path will not suffice.

Requiring a therapeutic agent to be provided with a sufficient collection of weaponry to conquer all barriers and still be small enough for safe vascular injection is a challenge uniquely suitable for nanotechnology.

As definition, nanotechnology-based devices must be of the nanoscale or have nanoscaled features, be man-made, and offer properties or functions made possible only through its minute size. Injected, nanoscale drug delivery systems, or nanovectors, are the ideal candidates to the time-honored problem of optimizing the therapeutic index for treatment; that is, to maximize efficacy, while reducing
health-adverse side effects.

A multistage nanovector approach may provide an elegant solution for delivering today’s drugs to the tumors of tomorrow. This strategy will require the integration of numerous particle technologies (i.e., liposome, carbon nanotube/buckeyball, metallic shells, dendrimers, etc.) and chemotherapeutics.
A conceptual prototype may utilize a carrier or “mothership” particle that is capable of releasing different stages of particles that are nested within one another and designed to circumvent different biobarriers and/or targeted release functions. A first embodiment of the strategy, designed for intravascular injec-
tion, may be conceptualized as follows: Stage One vectors are designed to travel through tumor capillaries and target cancer lesion vasculature. They will have different recognition moieties on their surface, including biologicals (aptamers,antibodies) and will feature detection and optimized adhesion strategies based on physical properties and charge distribution. Upon lodging in the tumor vasculature, they release preferentially penetration enhancers, and nanoparticles of Stage Two. The penetration enhancers could be directed against the basement membrane and/or toxins against the tight-junction proteins (TJP). The Stage Two nanoparticles are then allowed to penetrate across the basement membrane without constraint and selectively direct their cytotoxic payload against tumor cells. A very large number of possible embodiments for multistage nanovectors (i.e., particle type, size, shape, drug payload) could easily be envisioned and tailored to the biology of the biobarriers of interest, and through this, to the specific clinical applications.

นาโนเทคโนโลยี่ที่นำมาประยุกต์ใช้ ในการส่งผ่านยา (DRUG-DELIVERY SYSTEMS)

การประยุกต์ใช้นาโนพาร์ติเกิล ในการส่งผ่านยา

วัตถุประสงค์สำคัญของระบบการส่งผ่านยา 2 ประการ
2.การควบคุมอัตราการปลดปล่อย ณ.ตำแหน่งเป้าหมาย แบบควบคุมได้

An ideal drug-delivery system possesses two elements: the ability to target and to control the drug release. Targeting will ensure high efficiency of the drug and reduce the side effects, especially when dealing with drugs that are presumed to kill cancer cells but can also kill healthy cells when delivered to them. The reduction or preven- tion of side effects can also be achieved by controlled release. NPDDS provide a better penetration of the particles inside the body as their size allows delivery via intravenous injection or other routes. The nanoscale size of these particulate sys- tems also minimizes the irritant reactions at the injection site. Early attempts to direct treatment to a specific set of cells involved attaching radioactive substances to antibodies specific to markers displayed on the surface of cancer cells. Antibodies are the body’s means of detecting and flagging the presence of foreign substances. Antibodies specific to certain proteins can be mass produced in laboratories, ironi- cally using the cancer cells. These approaches have yielded some good results, and NPDDSs are demonstrating lot of potential in this area.

3.Solid Nanoparticles

3.1.Polyme-based nanoparticles
3.2.Lipid-based nanopaticles
3.3.Albumin nanopaticles

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