Kidney-Specific Drug Delivery: Review of Opportunities, Achievements, and Challenges

Kidneys are involved in essential complex procedures that maintain the body in equilibrium and preservethe interior environment necessary for life. Nephritis and nephrosis were ranked among the leading causes of death in all ages in the last global burden of disease assessment of the World Health Organization (WHO). Regarding kidney disease therapeutics, the unfavourable extra-target effects, the narrow therapeutic index, the inactivation of the drug before reaching its target, or the affected normal distribution due to the pathophysiology of diseases, all of these conducted to the requirement of new therapeutic aspects. An efficient kidney-specific drug delivery system will serve as fascinating approach and attractive option conquering such problems, improving the therapeutic index, and direct to a favourable pharmacokinetic profile of drugs. Such breakthrough in renal targeting will provide an efficacious major key for controlling the incidence of those problems, affording a logical treatment methodology managing all at-risk patients, representing a major intention for therapy and impart an attractive pharmacological implement to elucidate the mechanisms of drug action in the kidney.Several attempts to achieve the optimal renal delivery systems had been investigated; low-molecular-weight-proteins (LMWPs), low-molecular-weight chitosan (LMWC), Poly(vinylpyrrolidone-codimethyl maleic acid) (PVD), anionized polyvinylpyrrolidone (PVP), galectin-3 carbohydrate recognition domain (G3-C12), and most recently epsilon poly-Llysine-derivatives (εPLL) and the carrier peptide (KKEEE)3K. The majority of kidney-specific delivery systems target the proximal tubular cells. The specific uptake of the carriers by renal proximal tubular cells is attributed in many cases to megalin-mediated endocytosis. Moreover, the overall charge of the carrier seems to play a key role in kidney-specific drug delivery. On the other hand, mesangial cells represent a particularly suitable target for drug delivery by particulate drug delivery systems such as nanoparticles or liposomes taking into account the particle diameter. In this review, we summarize briefly the aforementioned issues.