Limits...
Drug delivery systems, CNS protection, and the blood brain barrier.

Upadhyay RK - Biomed Res Int (2014)

Bottom Line: Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics.In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained.Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, DDU Gorakhpur University, Gorakhpur 273009, India.

ABSTRACT
Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

Show MeSH

Related in: MedlinePlus

Showing presence of blood brain barrier at the blood capillary endothelium that obstructs drug delivery to CNS.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4127280&req=5

fig3: Showing presence of blood brain barrier at the blood capillary endothelium that obstructs drug delivery to CNS.

Mentions: After delivery of therapeutic biomaterials/pharmaceuticals in the brain its physiological accumulation is needed that plays a crucial role in the treatment of pathogenesis related to neuronal diseases [14]. Another important factor in drug delivery is lipid solubility of drug molecules/compounds that may move across the blood brain barrier by simple diffusion. There are few compounds which could increase the permeability of BBB by loosening the tight junctions between the endothelial cells [15]. Most psychoactive drugs increase the BBB permeability and decrease the physical restrictiveness of endothelial tight junctions and allow most of the therapeutic molecules to pass through the BBB in large amounts (Figure 3). But these drugs are highly invasive and should give only in controlled environment because of the risk of multiple effects. Moreover, over flooding of molecules in brain causes osmotic imbalances and largely affects membrane permeability and blocks or restricts normal supply of nutrients. Second, once tight junctions are loosened, the homeostasis of the brain gets thrown off which results in seizures and imposes compromised brain functions [15]. However, to treat the CNS diseases such as brain tumours, transport protein, peptides, radiopharmaceuticals and other macromolecules are allowed to pass across the blood brain barrier in a controlled concentration. For this purpose nanoparticle delivery methods are proved to be more promising than any other method available. These are most usable and noninvasive methods and proved to be much better than any other conventional method used for the treatment of neurological diseases [16]. Therefore, less toxic bioreversible derivatives of prodrugs, neurohealers, and pharmacological agents are urgently needed. These might enable the safe delivery of variety of drugs including anticancer, antineurodegenerative, and antiviral drugs. More specifically, more sophisticated nanoparticle based tools are required for the treatment of brain tumors, viral and neurodegenerative diseases, and disorders. Present review article aims to emphasize various applications of noninvasive drug delivery methods with recent developments which occurred in nanotherapeutics for CNS protection. Hence, special emphasis has been given to develop nontoxic delivery vehicles and highly soluble, permeable biocompatible anticancer drugs [17] and liposomal carriers to reduce the toxic effects and posttreatment fatalities in case of cancer and brain tumors [17, 18]. In addition, cellular mechanism of drug delivery such as receptor mediated endocytosis, microbubble enhanced focused ultrasound, proline rich peptides, chitosan based nanoparticles, beta-cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles delivery system, Si RA delivery system, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. In addition, suggestions have been given for designing much safer nontoxic delivery vehicles and biocompatible drugs to overcome the problem of clinical failures and posttreatment fatalities [19].


Drug delivery systems, CNS protection, and the blood brain barrier.

Upadhyay RK - Biomed Res Int (2014)

Showing presence of blood brain barrier at the blood capillary endothelium that obstructs drug delivery to CNS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127280&req=5

fig3: Showing presence of blood brain barrier at the blood capillary endothelium that obstructs drug delivery to CNS.
Mentions: After delivery of therapeutic biomaterials/pharmaceuticals in the brain its physiological accumulation is needed that plays a crucial role in the treatment of pathogenesis related to neuronal diseases [14]. Another important factor in drug delivery is lipid solubility of drug molecules/compounds that may move across the blood brain barrier by simple diffusion. There are few compounds which could increase the permeability of BBB by loosening the tight junctions between the endothelial cells [15]. Most psychoactive drugs increase the BBB permeability and decrease the physical restrictiveness of endothelial tight junctions and allow most of the therapeutic molecules to pass through the BBB in large amounts (Figure 3). But these drugs are highly invasive and should give only in controlled environment because of the risk of multiple effects. Moreover, over flooding of molecules in brain causes osmotic imbalances and largely affects membrane permeability and blocks or restricts normal supply of nutrients. Second, once tight junctions are loosened, the homeostasis of the brain gets thrown off which results in seizures and imposes compromised brain functions [15]. However, to treat the CNS diseases such as brain tumours, transport protein, peptides, radiopharmaceuticals and other macromolecules are allowed to pass across the blood brain barrier in a controlled concentration. For this purpose nanoparticle delivery methods are proved to be more promising than any other method available. These are most usable and noninvasive methods and proved to be much better than any other conventional method used for the treatment of neurological diseases [16]. Therefore, less toxic bioreversible derivatives of prodrugs, neurohealers, and pharmacological agents are urgently needed. These might enable the safe delivery of variety of drugs including anticancer, antineurodegenerative, and antiviral drugs. More specifically, more sophisticated nanoparticle based tools are required for the treatment of brain tumors, viral and neurodegenerative diseases, and disorders. Present review article aims to emphasize various applications of noninvasive drug delivery methods with recent developments which occurred in nanotherapeutics for CNS protection. Hence, special emphasis has been given to develop nontoxic delivery vehicles and highly soluble, permeable biocompatible anticancer drugs [17] and liposomal carriers to reduce the toxic effects and posttreatment fatalities in case of cancer and brain tumors [17, 18]. In addition, cellular mechanism of drug delivery such as receptor mediated endocytosis, microbubble enhanced focused ultrasound, proline rich peptides, chitosan based nanoparticles, beta-cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles delivery system, Si RA delivery system, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. In addition, suggestions have been given for designing much safer nontoxic delivery vehicles and biocompatible drugs to overcome the problem of clinical failures and posttreatment fatalities [19].

Bottom Line: Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics.In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained.Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, DDU Gorakhpur University, Gorakhpur 273009, India.

ABSTRACT
Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

Show MeSH
Related in: MedlinePlus