UNETHICAL RECRUITMENT OF PHYSICIANS
- RESEARCHER’S CONFLICTS OF INTEREST
- DATA MANIPULATION
- DRUG DELIVERY CARRIERS
- LIQUID CRYSTALS
- SOLID LIPID NANOPARTICLES (SLN)
- NANOSTRUCTURED LIPID CARRIERS (NLC)
- LIPID DRUG CONJUGATES (LDC) NANOPARTICLES
- LIQUID CRYSTAL DRUG DELIVERY SYSTEMS
In pharmaceutical industries, physicians are recruited by public relation firms. Endorsement of the clinical study by these physicians is another common problem. Ottawa Citizen, a reputed news source of Canada, reported that Dr. Davis Healy, a psychiatrist, was sent a finished review paper of 12 pages by a company to present it at a forthcoming conference as a sole author. Even though Healy declined the offer, the paper was presented at the conference under the name of another doctor (Spears, 2003). Several other cases were reported in which the physicians are offered to forward papers to medical journals in lieu of a considerable amount of money which is luring for some physicians and are denied by others for ethical, risky, and insecurity issues. Furthermore, with the increase by companies in investment, promotions, the value of these enticing offers could be tempting for physicians to accept and involve in such malpractices. This practice ruins the reputation of medical professionals and also put their reliability at a substantial risk.
RESEARCHER’S CONFLICTS OF INTEREST
Researchers’ financial conflict of interest (COI) has the perspective to influence results in corresponding studies. As mentioned by the ICMJE (International Council of Medical Journal Editors), COI mainly include consultancy, stock ownership, employment, honoraria, and patent licensing, excluding factors like financial relationships depending on grants, fellowships, awards, free equipment or drugs, and authors functioning as member of an advisory board or as a speaker (Friedman and Richter, 2004). Conflict issues can be challenged by writing a letter to Editor of the concerned journal. Interest may be academic, research or financial. Furthermore, COI is also arises when a person has a patent on the item and also publish the same in a journal.
Many reported piece of evidence suggests that various pharmaceutical companies tend to manipulate the clinical data in order to avoid the adverse results. Searle (2000) disclosed that Celebrex (celecoxib) is the first safe drug among COX-2 inhibitors than older NSAIDS (e.g., ibuprofen) for the treatment of gastrointestinal system. The claim was supposedly ciucial for both the patient as well as a marketer because approximately 107,000 annual hospitalizations due to gastrointestinal complications were reported for the consumption of arthritis drugs. Due to this, Celebrex became heavily marketed drug and the cost was increased up to rose to $2 per pill (Parker and Pettijohn, 2003). But later in 2004, a Group Health Cooperative of Seattle revised the protocol of the study carried out for FDA authorization. It showed that previously the results of only 6 months have been reported giving affirmative results while the 12-month results did not revealed any difference in gastrointestinal complications from other drugs (Brownlee, 2004; Rennie, 2004). Thus, discriminatory reportage of positive results is another common malpractice carried out by pharmaceutical companies for their benefits and has been reported many times.
DRUG DELIVERY CARRIERS
Colloidal drug transporter systems like micellar solutions, vesicle, and liquid crystal diffusions along with nanoparticle diffusions containing smaller particles of 10-400 nm diameters tend to show higher potential in drug delivery system. Property of a good earner desires enhanced drug loading and relief properties, long shelf-life and low toxicity. Microstructure of the system assisted by the incorporated drug may affect its molecular interactions particularly if the drug retains amphiphilic and/or mesogenic assets (Figure 12.2).
FIGURE 12.2 Different drug delivery carriers.
Micelles designed by the self-assembly of amphiphilic slab copolymers (5-50 nm) in aqueous solution are of great attention for drug delivery claims. These drugs actually can be trapped within the core of slab copolymer micelles and conveyed at concentration that enhances the intrinsic water solubility. Hydrophilic slabs usually create hydrogen bonds with the aqueous environment and tight shell of the micellar core results into formation of hydrophobic core. These properties efficiently protect against hydrolysis as well as degradation by enzymes. A final feature that makes amphiphilic slab copolymers gorgeous for the drug delivery is their easy alternations in chemical alignment, slab length ratios, and total molecular weight permitting permits size and morphology control of the micelles. Functionalization of slab copolymers with cross-linkable groups can upsurge the firmness of the consistent micelles and increase their progressive control.
Liposomes are a system of vesicles that contain either numerous or single phospholipid bilayer. Polar drug molecules are mainly condensed by polar personality of liposomal core. Both amphiphilic, as well as lipophilic molecules, are dissolved in phospholipid bilayer rendering to their affinity near phospholipids. Instead of phospholipids inside the bilayer formation, the contribution of non-ionic surfactants results in niosomes. Drugs that are encapsulated in a nanocage functionalized with channel protein are efficiently threatened from early deprivation by proteolytic enzymes. The drug molecule has diffusion potential through a concentration driven channel which functions on the basis of alterations in interior and exterior concentration of the nanocage.
Dendrimers are nanometer-sized, highly diverged and monodispersed macromolecules having symmetrical construction. They contain an essential core, split unit and terminal functional groups. The core is composed of interior units which regulates the environment of nanocavities and accordingly their solubilizing possessions whereas the exterior groups maintain solubility and chemical performance of these polymers. Targeting efficiency might altered and affected due to interaction of respective ligands at exterior surface of dendrimers while the defense from MPS (mononuclear phagocyte system). Its stability is accomplished by interaction of dendrimers with PEG (polyethylene glycol) chains.
Liquid crystals are available in both liquid and solid conditions. They can be formed in altered geometries, with alternative polar and non-polar layers (i.e., a lamellar phase) to comprise aqueous drug solutions.
Nanoparticles (counting nanospheres and nanocapsules of size 10-200 mn) are solid, either shapeless or crystalline. These nanoparticles are capable to encapsulate a drug. This practice protects the drug against chemical and enzymatic deprivation. Nanocapsules are vesicular systems to restrict the drug in a unique polymer membrane-enclosed cavity while nanospheres are generally the matrix system for actual and consistent drug dispersal. Nanoparticles could be composed of both decomposable polymers and non-decomposable polymers. Recently decomposable polymeric nanoparticles concerned attention as possible drug delivery strategies due to their function and application in the controlled announcement of drugs to target particular tissue or organ as the transporters of DNA in gene therapy as well as for their capacity to transport peptides, proteins or genes through the per oral way.
SOLID LIPID NANOPARTICLES (SLN)
Solid lipid nanoparticles (SLN) are particulate matter architecturally connected to polymeric nanoparticles. SLN, unlike the polymeric system, comprises of biocompatible lipids. They are well accepted for physiological in vivo administration and do not utilize organic solvents. These lipid matrices contain homolipids like fat or wax that deliver protection to the combined bioactive from chemical and physical deprivation, in addition to alteration in drug relief profile. Typical preparations involve lipids mainly paraffin wax or decomposable glycerides (e.g., Compritol 888 ATO) as the structural base of particle (Attama and Nkemnele, 2005). SLN have an ample and potential application in wide-field including brain, ocular, rectal, oral, topical, and vaccine delivery system, etc. Additionally, it also has better bioavailability, defends sensitive drug molecules from external environment, and even control the release of drug. Common drawbacks of SLN are random gelation tendency, particle growth, unpredicted dynamics of polymorphic transitions and intrinsic low integration rate because of the crystalline structure of solid lipid (Attama and Muller-Goymann, 2008).
NANOSTRUCTURED LIPID CARRIERS (NLC)
Nanostructured lipid carriers (NLC) are colloidal transporters categorized by a solid lipid core containing a solid and liquid mixture of lipids with the range of mean particle size in nanometers. They mainly contain a lipid matrix having a special nanostructure (Nair et al., 2011). This nanostructure recovers drug loading as it decisively recollects the drug during loading. NLC system reduces some difficulties related to SLN such a slow payload and drug exclusion on storage of certain drugs as well as the high content of water in SLN diffusion. Fresher approach to produce NLC is being established.
LIPID DRUG CONJUGATES (LDC) NANOPARTICLES
The main problem with SLN is the low ability to load hydrophilic drugs because of the separating property during construction procedure. Only, extremely effective low dosage of hydrophilic drugs might be appropriately combined inside the solid lipid matrix (Schwarz et al., 1994). To overcome this restriction, LDC nanoparticles with drug loading capabilities of up to 33% were developed. A bulk and insoluble drug-lipid conjugate is primarily prepared mainly by the salt formation or alternatively by covalent linking. The obtained LDC is administered along with an aqueous surfactant solution through high-pressure homogenization or HPH transformed to nanoparticle formulation by HPH. These nanoparticles possess possible application for brain as they might be used as hydrophilic drug in severe protozoan infections (Olbrich et al., 2002).
Transfersome machinery was developed with the purpose for providing a vehicle to permit bioactive molecule delivery via the dermal barrier. Transfersomes are basically ultra-deformable liposomes comprising of phospholipids plus additional edge active amphiphiles like bile salt sallow exciting alteration of the vesicle form. The vesicle diameter is about 100 mn when discreted in buffer (Cevc et al., 1998). These flexible vesicles are supposed to permeate through intact dermis layer completely with the help of hydrostatic gradient force existing in the skin. Antigen or drug may be combined into these vesicles in a way parallel to liposomes.
Non-ionic bilayer forming surfactants fonns niosomes are several vesicles. Niosomes are architecturally similar to liposomes but their synthesized surfactant has an advantage over phospholipids. Niosomes are meaningfully less expensive and have advanced chemical constancy than their naturally occurring phospholipid counterparts (Kazi et al., 2010). Different strategies such as hydration of synthetic non-ionic surfactants or in combination with cholesterol and other lipids are used toniosomes. Niosomes are usually comparable to liposome functionality which mainly deals with the increased bioavailability of drug and as decreased clearance, in a similar manner like liposomes. Niosomes can also be utilized for embattled drug delivery comparable to liposomes. The possessions of niosomes rest both on composition of the bilayer and method of production. Antigens along with minor molecules are transported using niosomes (Laksluni et al., 2007).
LIQUID CRYSTAL DRUG DELIVERY SYSTEMS
The nanostructured liquid crystalline resources are extremely stable at dilution which makes it easier to continue mainly as a slow and stored source of drug relief in excess body fluids including gastrointestinal tract or subcutaneous space. They may also discrete into nanoparticle form retaining the parent liquid crystalline structure. The rate of drug discharge is connected directly to the nanostructure of the matrix. Lyotropic liquid crystal systems generally contain amphiphilic molecules and solvents which can be categorized into lamellar (La), hexagonal, or cubic mesophases. The recent establishment of substantial attention of the lyotropic liquid crystal systems is mainly due to their outstanding vehicles ability for drug delivery (Guo et al., 2010). Out of these, reversed cubic (QII) and hexagonal mesophases (НИ) are the most significant and has been widely examined for then- capacity to bear the relief of a long range of bioactive compounds including drugs with lower molecular weight, peptide, protein, and nucleic acids.
Lipid-based design exists in a large range of elective delivery system like solution, suspension, self- emulsifying system, and nanoemulsions. Oral nanoemulsions offer a very decent substitute because it can recover the bioavailability of hydrophobic drugs by increasing its solubility. They are extensively used for the administration of both BCS class II and class IV drugs. Oral nanoemulsions use safe eatable material for fonnulation of delivery system. Nanoemulsions have outstanding capability to encapsulate active compounds due to their minor droplet dimension and huge kinetic firmness (Lovelyn and Attama, 2011).
- • conflict of interest
- • direct-to-consumer
- • high-pressure homogenization
- • lipid drug conjugates
- • maximum tolerated dose
- • mononuclear phagocyte system
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