type of urinary calculi constituting about 70–80% of the urinary or kidney stones

(Lin et al. 2017). Increased urinary super-saturation, predominantly of calcium

phosphate and calcium oxalate is responsible for the enhanced accumulation of

these salts in the renal tubules which ultimately lead to formation of kidney stones.

Apart from the formation of stones in the kidney, oxalate crystals can destruct

epithelium in the oral cavity and gastrointestinal tract, causing inflammation, diar-

rhea and gastric hemorrhage which indirectly becomes a cause of death (Gupta and

Kanwar 2020b). Although the introduction of modern techniques such as nephrec-

tomy, extracorporeal shock wave lithotripsy (ESWL) and drug treatment has

provided significant thrust toward the treatment of nephrolithiasis, but these treat-

ment options possess severe side effects such as traumatic effects, leading to acute

renal injury, hypertension, hemorrhage, a decrease in renal function and increased

chances of infection (Das et al. 2017). To effectively treat hyperoxaluria, oxalate

accumulation needs to be reversed, potentially by the systemic clearance of oxalate

(Zhao et al. 2017). Although the use of phytomolecules in the treatment and

management of kidney stones has been proposed by several in vivo and in vitro

studies and clinical trials, interestingly, this has emerged as a novel option, but much

research is still needed to effectively curb the disease (Gupta and Kanwar 2018).

Enzymatic dissolution of oxalate stones may provide a potential therapeutic

alternative, and much work has been done in this sphere. Till date three major

oxalate-degrading enzymes have been reported, namely, oxalate decarboxylase

(ODC, oxalate carboxylyase, EC 4.1.1.2), oxalate oxidase (OXO, oxalate:oxygen

oxidoreductase,

EC

1.2.3.4)

and

oxalyl-CoA

decarboxylase

(oxalyl-CoA

carboxylyase, EC 4.1.1.8) (Gupta and Kanwar 2020b). Oxalate decarboxylase,

specifically acting on oxalate, degrades it into most soluble products, CO2 and

formate (Pierzynowska et al. 2017). The enzyme is a homogenous polymerase

with manganese ion and belongs to the cupin protein superfamily (Dunwell and

Purvis 2004). Since its discovery the enzyme has been found in a number of fungal

and bacterial species and can be an extremely assuring therapeutic for the clearance

of oxalate and hence the treatment of hyperoxaluria and nephrolithiasis. Although

these enzymes possess strong therapeutic abilities against nephrolithiasis, with

respect to kidneys, most therapeutic molecules exhibit poor pharmacokinetics, and

their persistence in the kidneys is too brief to display a therapeutic effect (Williams

et al. 2016). This limitation can be overcome by development of enzyme

nanoparticles (NPs).

13.3

Nanodrugs for Nephrolithiasis

Nanoparticles (NPs) are nanosized colloidal particles, in which a drug is

encapsulated, entrapped or attached to the NP matrix (Maurya et al. 2019). Along

with the speculations that NPs may prevent the unenviable side effects and surpass

various physiological and physical barriers usually experienced during systemic

drug administration, these are becoming critically significant as an applicable tool

13

Nanodrugs: A Futuristic Approach for Treating Nephrolithiasis

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