title: Levodopa delivery systems: advancements in delivery of the gold standard.
abstract: BACKGROUND
  Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors.
  
  
  METHODS
  Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated.
  
  
  RESULTS
  The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated.
  
  
  CONCLUSIONS
  This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the effective management of PD.
authors.affiliation: University of the Witwatersrand, Department of Pharmacy and Pharmacology, 7 York Road, Parktown, 2193, Johannesburg, South Africa.
authors.forename: Ndidi
authors.initials: N
authors.lastname: Ngwuluka
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Du Toit
authors.forename: Valence
authors.initials: V
authors.lastname: Ndesendo
authors.forename: Yahya
authors.initials: Y
authors.lastname: Choonara
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.forename: Dinesh
authors.initials: D
authors.lastname: Naidoo
mesh_terms: D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004304:Dosage Forms; D004333:Drug Administration Routes; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008954:Models, Biological; D008959:Models, Neurological; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D004304:Dosage Forms; D007980:Levodopa