Recent Advances in Intravesical Drug/Gene Delivery

Abstract

Targeting of the drugs administered systemically relies on the higher affinity of ligands for specific receptors to obtain selectivity in drug response. However, achieving the same goal inside the bladder is much easier with an intelligent pharmaceutical approach that restricts drug effects by exploiting the pelvic anatomical architecture of the human body. This regional therapy involves placement of drugs directly into the bladder through a urethral catheter. It is obvious that drug administration by this route holds advantage in chemotherapy of superficial bladder cancer and it has now become the most widely used treatment modality for this ailment. In recent years, the intravesical route has also been exploited either as an adjunct to an oral regimen or as a second-line treatment for neurogenic bladder 1, 2 . Instillation of DNA via this route using different vectors has been able to restrict the transgene expression in organs other than bladder. The present review article will discuss the shortcomings of the current options available for intravesical drug delivery (IDD) and lay a perspective for future developments in this field.

Intravesical gentamicin for recurrent urinary tract infection in patients with intermittent bladder catheterisation

“…This layer is known to exhibit a tough barrier function that allows the instillation of potentially toxic drugs to achieve a localised pharmacological effect whilst avoiding systemic effects [19]. Diffusion of aminoglycosides across the uroepithelium is even more limited because of their polar cationic nature.…”

Preclinical evaluation of a gene therapy treatment for transitional cell carcinoma

“…1 Besides the uroplakins-rigid plaques covering the round surfaces of apical cells-the mucin layer, which overlies the uroplakins and is composed of GAGs, further augments the strength of the permeability barrier, which acts by physically blocking instilled drug molecules from reaching the underlying tight junctions and cell membrane. 45 It is possible that the layers of uroplakins and mucin acted to prevent the absorbance of celecoxib, greatly reducing its therapeutic effects.…”

“…Moreover, the high surface to volume ratio of the PEI nanoparticles may have also had a role in the transvesical absorption of encapsulated gene delivery complexes. 45 The destruction of GAG and uroplakin layers through electrocautery can be eliminated as reasons for successful gene delivery. Figure 4 demonstrates that unmodified PEI/DNA complexes can successfully transfect intact murine bladder.…”

Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice

“…Subsequently, this drug has been explored increasingly more intensively and gradually more widely used. Current clinical studies have demonstrated that drugs with liposome as a carrier have advantages such as immunogenicity, insignificant toxicity and side effects, as well as easy adsorption (Tyagi et al, 2006). At present, doxorubicin, containing liposome as a drug carrier in the treatment of cancer, has been mainly divided into pegylated liposomal doxorubicin (PLD) and non-PLD (NPLD), the major difference being whether a polyethylene glycol-modified agent is contained or not.…”