Table 3 Drugs with areas of opportunity for reformulation in NPs for PD

Exenatide

3–Recruiting

2–Active

1–Terminated

1–Unknown

Yes

Polymeric NPs/CSK-DEX-PLGA [128]

Rapidly eliminated by glomerular filtration, reformulation in NPs could increase its half-life in plasma and avoid enzymatic degradation

Levetiracetam

3–Terminated

1–Suspended

1–Recruiting

1–Unknown

Yes

Polymeric NPs/PLGA [129]

Reformulation in NPs could reduce the dose and administration frequency, reducing side effects

Semaglutide

1–Not yet recruiting

No

Liposome/Phospholipid- cholesterol [130]

NPs could improve stability, bioavailability, and passage through the BBB and avoid toxic accumulation due to its half-life of approximately one week

Vitamin B12

1–Terminated

Yes

Lipid-protein NPs/Barley protein-α-tocopherol-Phospholipids [131]

Reformulate in NPs with surface functionalization allows their targeting to the brain

Pomalidomide

N/I

Restricted

(P-gp substrate)

N/I

BCS class IV, reformulation in NPs could improve intestinal absorption and permeability through the BBB

Dabrafenib

N/I

Restricted

(P-gp substrate)

N/I

Reformulation in NPs with anti-P-gp surface functionalization could allow passage through the BBB

Ketoconazole

N/I

Restricted

(P-gp substrate)

Polymeric NPs/PLGA [132]

Low solubility. Reformulation in NPs could offer a controlled release, reduce toxic effects, and achieve greater bioavailability

Felodipine

N/I

Yes

Polymeric NPs/PLGA [133]

SLN/Glyceryl behenate [134]

Variable bioavailability, poor solubility, and extensive liver metabolism. Reformulation in NPs could offer greater brain bioavailability

Raloxifene

N/I

Yes

Polymeric NPs/CS [135]

SLN/Glyceryl behenate [136]

Low oral bioavailability, poor solubility, and extensive metabolism in the intestine (> 90%). Reformulation in NPs could improve oral bioavailability

Candesartan

N/I

Yes

SLN/Trimyristin-Tripalmitin-Tristearin [137]

Low oral bioavailability, poor solubility. Reformulation in NPs could improve oral bioavailability and target the brain

Telmisartan

N/I

Yes

(dose-dependent)

Polymeric NPs/PLA [138]

Low oral bioavailability, poor solubility. NPs could allow greater penetration of the BBB and target the brain

Nitazoxanide

N/I

Low permeability

SLN/Hydrogenated palm oil- Hydrogenated soybean lecithin [139]

Reformulation in NPs could allow more passage through the BBB, greater control of the dosage, and avoid toxic effects

Metformin

N/I

Yes

Polymeric NPs/Alginate [140]

BCS class III, low absorption. Reformulation in NPs could facilitate absorption and control the dosage and release at the specific site of action

Nilotinib

1 – Active

2 – Terminated

Low permeability

Polymeric micelles/Styrene-co-maleic acid [141]

Low exposure to CSF limits its use in PD. Reformulation in functionalized NPs could allow vectorization towards the CNS

Exemestane

N/I

Yes

Polymeric NPs/Alginate [142]

Reformulating in NPs could improve solubility and bioavailability, control release, and decrease side effects

Salbutamol

N/I

Yes

Polymeric NPs/PLGA, and poly(vinyl sulfonate-co-vinyl alcohol)-graft-PLGA [143]

Low oral bioavailability. Reformulation in NPs could allow the targeting of the target neurons

Pentamidine

N/I

Low permeability

Polymeric NPs/PLGA [144]

Liposome/Phosphatidylcholine

Polymeric NPs/PCL [145]

It can cause diabetes and other toxic effects. Reformulation in NPs could improve permeation through the BBB, greater control of the dosage, and avoiding toxic effects

Ceftriaxone

1 – Recruiting

Yes

Polymeric NPs/CS [146]

It is administered parenterally. Only 1% oral bioavailability, reformulation in NPs could increase its bioavailability and allow a controlled release

Vilazodone

N/I

Restricted

(P-gp substrate)

Polymeric NPs/Copolymer Soluplus^®-Polyvinylpyrrolidone [147]

Low solubility. Reformulation in NPs could increase bioavailability and permeation through the BBB

Methylene blue

N/I

Yes

Metallic NPs/Ag [148]

Rapid distribution in tissues. Severe toxicity in high doses. Reformulation in NPs could allow controlled dosage and vectorization towards the CNS

Nalbuphine

N/I

Yes

SLN/Phosphatidylcholine [149]

They are limited to parenteral use. High concentrations can cause sedation. Reformulation of NPs could allow oral administration and greater dosage control

Ketamine

N/I

Yes

Polymeric NPs/PEG-PLGA [150]

Short half-life. Serious adverse effects. Reformulation in NPs could increase their bioavailability and specific release in target neurons

Dimethyl fumarate

N/I

Low permeability

SLN/Tocopherol acetate [151]

Short half-life. Reformulation in NPs could improve bioavailability, brain permeability and reduce adverse effects

Kanamycin

N/I

Low permeability

Metallic NPs/Au [152]

Relatively insoluble in lipids. Reformulation in NPs could allow greater oral bioavailability and permeation through the BBB

CMT-3

N/I

Yes

N/I

Multi-target drug. Reformulation in NPs could allow targeting of target neurons

Doxycycline

N/I

Yes

Polymeric NPs/PLGA-PCL (153)

Reformulation in NPs would allow the sustained administration of the drug, minimizing adverse effects