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Novel targeted bladder drug-delivery systems: a review.

Zacchè MM, Srikrishna S, Cardozo L - Res Rep Urol (2015)

Bottom Line: The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects.DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance.We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Urogynaecology, King's College Hospital, London, UK.

ABSTRACT
The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy.

No MeSH data available.


Related in: MedlinePlus

Structure of the urinary bladder wall and urothelium.Abbreviation: GAG, glycosaminoglycan.
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f1-rru-7-169: Structure of the urinary bladder wall and urothelium.Abbreviation: GAG, glycosaminoglycan.

Mentions: The bladder is a hollow elastic organ that accommodates and stores urine, and facilitates voiding at appropriate intervals. Its size varies during filling, and normal capacity is ~500 mL. Inner aspect of the bladder is lined by the urothelium, which is crucial in order to design effective intravesical drug delivery (IDD). It is a stratified epithelium, also known as transitional epithelium, with a layer of unique “umbrella cells” forming the luminal surface.5 These cells can flatten and increase surface area with stretching.6 Umbrella cells are covered by rigid plaques, composed of four major uroplakins, UPIa (27 kDa), UPIb (28 kDa), UPII (15 kDa), and UPIII (47 kDa).7 The impermeability of the urothelium is further augmented by glycosaminoglycans (GAGs), which form a mucin hydrophilic layer adherent to the luminal side.8 These GAGs form a very tight barrier, capable of facing potentially noxious levels of urea, ammonia, and other toxic metabolites for prolonged periods of time. The function of this barrier is similar to the blood–brain barrier, with the only difference that the bladder is a storage organ, and needs to be more resistant to the passage of molecules. This is also known as the bladder permeability barrier (BPB) and represents an important obstacle in the success of IDD (Figure 1).9


Novel targeted bladder drug-delivery systems: a review.

Zacchè MM, Srikrishna S, Cardozo L - Res Rep Urol (2015)

Structure of the urinary bladder wall and urothelium.Abbreviation: GAG, glycosaminoglycan.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664547&req=5

f1-rru-7-169: Structure of the urinary bladder wall and urothelium.Abbreviation: GAG, glycosaminoglycan.
Mentions: The bladder is a hollow elastic organ that accommodates and stores urine, and facilitates voiding at appropriate intervals. Its size varies during filling, and normal capacity is ~500 mL. Inner aspect of the bladder is lined by the urothelium, which is crucial in order to design effective intravesical drug delivery (IDD). It is a stratified epithelium, also known as transitional epithelium, with a layer of unique “umbrella cells” forming the luminal surface.5 These cells can flatten and increase surface area with stretching.6 Umbrella cells are covered by rigid plaques, composed of four major uroplakins, UPIa (27 kDa), UPIb (28 kDa), UPII (15 kDa), and UPIII (47 kDa).7 The impermeability of the urothelium is further augmented by glycosaminoglycans (GAGs), which form a mucin hydrophilic layer adherent to the luminal side.8 These GAGs form a very tight barrier, capable of facing potentially noxious levels of urea, ammonia, and other toxic metabolites for prolonged periods of time. The function of this barrier is similar to the blood–brain barrier, with the only difference that the bladder is a storage organ, and needs to be more resistant to the passage of molecules. This is also known as the bladder permeability barrier (BPB) and represents an important obstacle in the success of IDD (Figure 1).9

Bottom Line: The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects.DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance.We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Urogynaecology, King's College Hospital, London, UK.

ABSTRACT
The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy.

No MeSH data available.


Related in: MedlinePlus