Girish Modi

Burden of stroke in black populations in sub-Saharan Africa

Sub-Saharan Africa is undergoing epidemiological transition. Stroke and other vascular diseases increasingly contribute to the burden of disease. There are no systematic reviews of stroke mortality, prevalence, incidence, and case fatality. We combined a thorough search and critical assessment of the published research. Stroke mortality is as high, perhaps higher, than in high-income regions and increases with age in sub-Saharan Africa as in high-income countries, but the absolute number of stroke deaths remains low. There are no adequate community-based stroke incidence studies. Hospital-based incidence is lower than in high-income regions, but higher in young people, possibly due to hospital admission bias. There are no community-based data on case fatality, but hospital-based case fatality is higher than elsewhere. The prevalence of stroke is lower than in high-income regions, but disabling stroke is as prevalent. As the region develops economically, the incidence of stroke and other vascular diseases will increase unless interventions are implemented. Only community-based incidence studies will accurately reveal the burden of stroke.

A Review on Composite Liposomal Technologies for Specialized Drug Delivery

The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications.

Current advances in the fabrication of microneedles for transdermal delivery

The transdermal route is an excellent site for drug delivery due to the avoidance of gastric degradation and hepatic metabolism, in addition to easy accessibility. Although offering numerous attractive advantages, many available transdermal systems are not able to deliver drugs and other compounds as desired. The use of hypodermic needles, associated with phobia, pain and accidental needle-sticks has been used to overcome the delivery limitation of macromolecular compounds. The means to overcome the disadvantages of hypodermic needles has led to the development of microneedles for transdermal delivery. However, since the initial stages of microneedle fabrication, recent research has been conducted integrating various fabrication techniques for generating sophisticated microneedle devices for transdermal delivery including progress on their commercialization. A concerted effort has been made within this review to highlight the current advances of microneedles, and to provide an update of pharmaceutical research in the field of microneedle-assisted transdermal drug delivery systems.

Nanotechnological applications for the treatment of neurodegenerative disorders.

Nanotechnology employs engineered materials or devices that interact with biological systems at a molecular level and could revolutionize the treatment of neurodegenerative disorders (NDs) by stimulating, responding to and interacting with target sites to induce physiological responses while minimizing side-effects. Conventional drug delivery systems do not provide adequate cyto-architecture restoration and connection patterns that are essential for functional recovery in NDs, due to limitations posed by the restrictive blood-brain barrier. This review article provides a concise incursion into the current and future applications of nano-enabled drug delivery systems for the treatment of NDs, in particular Alzheimers and Parkinsons diseases, and explores the application of nanotechnology in clinical neuroscience to develop innovative therapeutic modalities for the treatment of NDs.

Stroke in Black South African HIV-Positive Patients: A Prospective Analysis

Background and Purpose— Stroke associated with HIV infection is poorly characterized. In this study we analyze the association in a black African population. Methods— The clinical, laboratory, and radiological characteristics of 35 hospital-based black South African, heterosexual, HIV-infected patients who did not abuse intravenous drugs and presented with strokes were prospectively studied. The patients were antiretroviral therapy naive. Patients with other intracranial space-occupying lesions were excluded from the study. Results— The age range was 20 to 61 years (mean, 32.1 years). There were 21 female and 14 male patients, with a female to male ratio of 1.5:1. Cerebral infarction occurred in 33 patients (94%) and intracerebral hemorrhage in 2 patients (6%). Underlying causes were identified in 30 of the 35 patients (86%) and included coagulopathies, meningitis, cardioembolism, and hypertension. The most common coagulopathy was protein S deficiency. No cause was found in 5 patients (14%). Conclusions— The results are similar to data from studies on young black African stroke patients who are HIV negative.

Advances in the treatment of neurodegenerative disorders employing nanotechnology

Due to limitations posed by the restrictive blood–brain barrier, conventional drug delivery systems do not provide adequate cyto‐architecture restoration and connection patterns that are essential for functional recovery in neurodegenerative disorders (NDs). Nanotechnology employs engineered materials or devices that interact with biological systems at a molecular level and could revolutionize the treatment of NDs by stimulating, responding to, and interacting with target sites to induce physiological responses while minimizing side effects. This review provides a concise discussion of the current applications of nano‐enabled drug‐delivery systems for the treatment of NDs, in particular Alzheimers and Parkinsons diseases, and explores the future applications of nanotechnology in clinical neuroscience to develop innovative therapeutic modalities for the treatment of NDs.

Differences in the Nature of Stroke in a Multiethnic Urban South African Population The Johannesburg Hospital Stroke Register

Background and Purpose— The burden of stroke is increasing in Sub-Saharan Africa (SSA) as the population undergoes epidemiological and demographic transition. Little is known about the nature (risk factors, stroke type and subtype, and causes) of stroke in SSA and whether it differs from stroke in high-income populations. We aimed to compare the nature of stroke between black and white populations in South Africa. Methods— We used overlapping sources to ascertain consecutive first-ever-in-a-lifetime stroke patients admitted to Johannesburg Hospital over 23 months. We assessed each patient’s demographic details, risk factors, CT confirmed pathological stroke type, ischemic stroke subtype and stroke severity, and compared the nature of stroke between black and white stroke patients. Results— 524 patients with presumed stroke were referred. Of these, 432 were first-ever strokes; 308 patients were black and 76 white. Black patients were significantly younger (mean age 51) than white patients (61). Stroke severity was similar (median NIH stroke score 10; 95% CI 8 to 11). More black than white patients had cerebral hemorrhage (27% versus 15%), lacunar stroke (28% versus 22%) and total anterior circulation infarcts (28% versus 22%). Large vessel atherosclerosis (none detected) and ischemic heart disease were very uncommon (1%) as a cause of stroke in black patients. Hypertension (70% versus 68%) and diabetes (14 versus 15%) were as common in black and white stroke patients, but mean cholesterol levels were lower (4.6 mmol/L; 95% CI 4.3 to 4.9 versus 5.3 mmol/L; 4.8 to 5.7) and cigarette smoking less frequent in black patients (23 versus 54%). Conclusions— Although this was a hospital-based study, the difference in the nature of stroke between black and white stroke patients likely reflects the profile of stroke risk factors. There is an opportunity to prevent an otherwise inevitable increase in atherosclerotic stroke (and IHD) by targeting dietary and smoking habits in the black South African population.

In Silico Theoretical Molecular Modeling for Alzheimer’s Disease: The Nicotine-Curcumin Paradigm in Neuroprotection and Neurotherapy

The aggregation of the amyloid-β-peptide (AβP) into well-ordered fibrils has been considered as the key pathological marker of Alzheimer‘s disease. Molecular attributes related to the specific binding interactions, covalently and non-covalently, of a library of compounds targeting of conformational scaffolds were computed employing static lattice atomistic simulations and array constructions. A combinatorial approach using isobolographic analysis was stochastically modeled employing Artificial Neural Networks and a Design of Experiments approach, namely an orthogonal Face-Centered Central Composite Design for small molecules, such as curcumin and glycosylated nornicotine exhibiting concentration-dependent behavior on modulating AβP aggregation and oligomerization. This work provides a mathematical and in silico approach that constitutes a new frontier in providing neuroscientists with a template for in vitro and in vivo experimentation. In future this could potentially allow neuroscientists to adopt this in silico approach for the development of novel therapeutic interventions in the neuroprotection and neurotherapy of Alzheimer‘s disease. In addition, the neuroprotective entities identified in this study may also be valuable in this regard.

Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain.

This study focused on the design, biometric simulation and optimization of an intracranial nano-enabled scaffold device (NESD) for the site-specific delivery of dopamine (DA) as a strategy to minimize the peripheral side-effects of conventional forms of Parkinsons disease therapy. The NESD was modulated through biometric simulation and computational prototyping to produce a binary crosslinked alginate scaffold embedding stable DA-loaded cellulose acetate phthalate (CAP) nanoparticles optimized in accordance with Box-Behnken statistical designs. The physicomechanical properties of the NESD were characterized and in vitro and in vivo release studies performed. Prototyping predicted a 3D NESD model with enhanced internal micro-architecture. SEM and TEM revealed spherical, uniform and non-aggregated DA-loaded nanoparticles with the presence of CAP (FTIR bands at 1070, 1242 and 2926 cm(-1)). An optimum nanoparticle size of 197 nm (PdI=0.03), a zeta potential of -34.00 mV and a DEE of 63% was obtained. The secondary crosslinker BaCl(2) imparted crystallinity resulting in significant thermal shifts between native CAP (T(g)=160-170 degrees C; T(m)=192 degrees C) and CAP nanoparticles (T(g)=260 degrees C; T(m)=268 degrees C). DA release displayed an initial lag phase of 24 h and peaked after 3 days, maintaining favorable CSF (10 microg/mL) versus systemic concentrations (1-2 microg/mL) over 30 days and above the inherent baseline concentration of DA (1 microg/mL) following implantation in the parenchyma of the frontal lobe of the Sprague-Dawley rat model. The strategy of coupling polymeric scaffold science and nanotechnology enhanced the site-specific delivery of DA from the NESD.

Self-assembling peptides: implications for patenting in drug delivery and tissue engineering.

In this paper, a comprehensive review of recent patents concerning the molecular self-assembly of peptides, peptide amphiphiles and peptidomimetics into molecules through nanoarchitectures to hydrogels is provided. Their potential applications in the field of drug delivery and tissue engineering have been highlighted. The design rules of this rapidly growing field are centered mainly on the construction of peptides in the form of peptide amphiphiles, aromatic short peptide derivatives, all-amino acid peptide amphiphiles, lipidated peptides with single and multiple alkyl chains and peptide-based block copolymers and polymer peptide conjugates. The interest in patenting of self-assembling peptides is also driven by their type (I, II, III and IV) and their ability to form well-regulated highly-ordered structures such as β-sheets/β-hairpins, α-helices/coiled coils and to hierarchically self-organize into supra-molecular structures. The applicability of these systems in cell culture scaffolds for tissue engineering, drug and gene delivery and as templates for nanofabrication and biomineralization has inspired various groups over the globe. This resulted in development of self-assembling peptides as synthetic replacements of biological tissues, designing materials for specific medical applications, and materials for new applications such as diagnostic technologies. Furthermore, biologically derived and commercially available systems are also discussed herein along with a brief account of various awarded and pending patents in the past 10 years. An overview of the diversity of the patent applications is also provided for self-assembling systems based on nano- and/or micro-scale such as fibers, fibrils, gels, hydrogels, vesicles, particles, micelles, bilayers and scaffolds.