Review Article

Feasibility Assessment of Transdermal Drug Delivery Systems for Treatment of Parkinson's Disease

Nida Akhtar and Kamla Pathak*
Department of Pharmaceutics, Uttar Pradesh University of Medical Sciences, India


*Corresponding author: Kamla Pathak, Department of Pharmaceutics, Uttar Pradesh University of Medical Sciences, India


Published: 07 Sep, 2017
Cite this article as: Akhtar N, Pathak K. Feasibility Assessment of Transdermal Drug Delivery Systems for Treatment of Parkinson's Disease. Ann Pharmacol Pharm. 2017; 2(17): 1090.

Abstract

Parkinson’s disease (PD) is defined as the second most prevalent neurodegenerative disorder that has been characterized with a loss of dopaminergic neurons severely in cytoplasmic inclusions and substantia nigra. To treat both early and advanced stages of PD several therapeutic agents are available. However, the transport of therapeutic actives in to the brain has been a consistent challenge for researchers, because of the presence of blood-brain barrier (BBB). Various novel delivery carriers have been designed to deliver the drugs across BBB and the systems have been designed with an object to effectively target the drugs and overcoming the BBB. In some last decades, transdermal delivery carriers have gained extensive deliberations across the globe. These transdermal systems are depicted to be the most recent modalities in treating PD as they offer constant drug delivery, immediate effect as intestinal absorption in unneeded, and ease of application being a non-invasive technique. The present review explores the potential of transdermal delivery systems in order to deliver numerous therapeutic actives researched for PD therapy viatransdermal route. Various trans-carriers such as patches, oil-based nanocarriers, nanoemulsions have been observed for the treatment of PD. The write up traces the reports on transdermal delivery carriers in PD and clinical study data to define the feasibility transdermal carriers.
Keywords: Transcarriers; Transdermal delivery; Parkinson’s disease; Drug delivery systems; Clinical status


Introduction

Parkinson’s disease (PD) is defined as a chronic and progressive neurological disease that has been characterized with the symptoms of stiffness, tremors, and slow or hesitant speech. Though the disease is most commonly related and seen in old aged people, it has been reported that around one in ten people are diagnosed with the disease before the age of 50. Parkinson’s disease is depicted by striatal dopamine depletion as a result of dopaminergic neurons degeneration in the substantia nigra pars compacta. Besides the lack of dopamine at the cellular level the formation of Lewy bodies in the substantia nigra, which are cytoplasmic inclusions composed of fibrils, ubiquitin, and alpha-synuclein may appear [1,2]. Medication employed for the treatment of PD only provides patients with temporary symptomatic relief, where access to care and treatment differs widely depending on where the patients live [3]. Pharmaceutical agents that are used to treat PD include levodopa, entacapone, pramipexole, ropinrole, benserazide, carbidopa, tolcapone, entacapone, selegiline, rasagiline, and safinamide [4]. However, several drugs among these are not able to reach the brain completely and can undergo metabolism instead, partially or completely by liver. This inefficient utilization of drug may require ingestions of higher drug concentrations that can produce toxic effects in the heart, liver, or kidney. Also, many therapeutic agents are poorly soluble or insoluble in aqueous solutions. These drugs provide challenges to deliver them orally or parentally, however, these compounds can have significant benefits when formulated through other delivery systems like transdermal systems [5].
Transport of therapeutic actives via transdermal route is a well established route of administration valued by patients as well as physicians for comfort and convenience [6]. Drug transport via transdermal route has been approved and widely accepted for the systemic drug delivery.This non-invasive approach avoids the hepatic first-pass metabolism, maintains a steady drug concentration (extremely important both in the case of drugs with a short half-life and in the case of chronic therapy), allows the use of drugs with a low therapeutic index, and improves patient compliance. However, the outermost layer of the skin, stratum corneum prevents transdermal permeation of most drugs at clinically useful rates. To facilitate this transdermal transport of drugs, numerous systems have been investigated to treat PD.


Table 1

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Table 1
Effective transdermal delivery of therapeutic actives via novel carriers in treating PD.

Parkinson’s Disease and Its Treatment Approaches

Parkinson’s relates to a category of neurodegenerative disorders that affects several brain regions, including pigmented nuclei in the midbrain and brainstem, cerebral cortex, olfactory tubercle, and peripheral nervous system [7]. The pathological and clinical manifestations of PD include depletion of dopaminergic neurons in the midbrain, and deficiency of dopamine in the areas of brain areas that receive dopaminergic inputs from these neurons [8]. Clinically, the indications of the disease can be grouped into motor, cognitive and psychiatric; each group with its own set of symptoms. The usual occurrence of PD in late midlife or marked increase is prevalent at older ages, suggests the possible role of aging in the pathogenesis of PD [9]. Many cellular mechanisms are believed to be involved in neuronal death in PD, such as endoplasmic reticulum stress, proteasomal and mitochondrial dysfunction [10].
Treatments are effective in managing the early motor symptoms of the disease, mainly through the use of levodopa (L-DOPA) and dopamine agonists. As the disease advances and dopaminergic neurons continue to get depleted, these drugs eventually become ineffective in treating the symptoms, and at the same time produce a complication called dyskinesia, marked by involuntary writhing movements; thereby making the treatment difficult. More recently, nose to brain delivery of nanoformulations and transdermal systems have gained tremendous potential to provide effective therapy in treating PD. Nano-formulations delivered via nose to brain route are the upcoming formulations in PD treatment as they offer targeted drug delivery, enhanced therapeutic efficacy and decreased systemic side effects of neurotherapeutics. These formulations provide effective intranasal transport by encapsulating drug, protecting it from biological/ chemical degradation and extracellular transport through P-glycoprotein (P-gp) efflux thus, and enhancing CNS availability for drugs as highlighted in our extensive published review article [11]. However, in the preceding text transdermal systems has been highlighted for treating PD.


Transdermal Therapy in PD

Skin is the largest and easily accessible organ of the body and therefore can be extensively used as a prominent route of delivery for local and systemic effects. Though it presents a multifunctional barrier between body and surrounding particles, there are chances to deliver therapeutic carriers, particularly in diseased skin. For dermal and transdermal drug delivery, the horny layer, i.e, the uppermost layer of the skin serve as the most resistant layer to be crossed. To circumvent this barrier, different perforation techniques are used that relatively widen the skin opening and allow the passage of drug (≤ 10 mg) and micromolecules, but this amateur disruption of the skin can be avoided in order to preserve this barrier against cutaneous microbiota by using deformable carriers [12]. Transdermal drug delivery system (TDDS) in this context provides a means to sustain drug release as well as reduce the intensity of action and thus minimize the side effects associated with its oral therapy. Transdermal systems are self-contained, discrete dosage form. It delivers a drug through intact skin at a controlled rate into the systemic circulation. Delivery rate is controlled by the skin or membrane in the delivery system.
Various transdermal drug delivery systems have been developed to treat PD using several carriers, penetration enhancers and vehicle based system. The most commonly used transdermal system is the skin patch using various types of technologies. Formulations designed to deliver the drug at optimized rate into the systemic circulation should adhere to the skin for the expected duration and should not cause any skin irritation and/or sensitization, enhance the bioavailability and minimize the pharmacokinetic peaks and troughs [13]. The transdermal systems that have been explored till date for treating PD are highlighted in Figure 1. Table 1 revealed the reports based on these explored carriers in treating PD in recent years.


Figure 1

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Figure 1
Various approaches for transdermal delivery in the treatment of Parkinson’s disease.

Table 2

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Table 2
Clinical development in the treatment of Parkinson’s disease via transdermal systems.

Clinical Status of Intranasal Delivery

Clinical trials reported on transdermal delivery systems are initiated with the finding that drugs administered via transdermal route could effectively deliver the therapeutic actives. Table 2lists the clinical status of various drugs used in PD.


Conclusion

Transdermal drug delivery has proved to be an important treatment approach that is not only capable of providing a constant rate of drug delivery, but is also non-invasive and relatively simple to use. However, developing a drug to be delivered transdermally for the treatment of PD has been anything but easy. The techniques designed to enhance skin permeation and to improve the effectiveness of transdermal drug delivery are also potential sources for future treatment advances. Clinical trials of the said systems affirm their position in PD therapeutics.


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