Syed A. Rizvi

Formulation and evaluation of drug-loaded targeted magnetic microspheres for cancer therapy

Enhanced and targeted drug delivery using biodegradable microspheres is emerging as a promising approach for cancer therapy. The main objective of the present research was to formulate, characterize, and evaluate iron oxide (magnetic) containing a bovine serum albumin-based microsphere drug delivery system, capable of efficiently delivering sulforaphane, a histone deacetylase inhibitor, for an extended period of time in vivo. Magnetic microspheres were prepared by spray-drying and characterized for their physicochemical properties and dissolution profile. Further, they were evaluated for therapeutic efficacy in in vitro and in vivo systems. In vitro studies in B16 melanoma cells revealed that there was about 13%–16% more inhibition of cell viability when either 30 μM or 50 μM of sulforaphane was used with iron oxide in the polymeric carrier. Data from in vivo studies in C57BL/6 mice revealed that the magnetic microspheres (localized to the tumor site with the help of a strong magnet) inhibited 18% more tumor growth as compared with sulforaphane in solution. In addition, there was a 40% reduction in histone deacetylation levels in mice treated with iron oxide microspheres containing sulforaphane. Thus, magnetic microspheres are shown to be an effective drug delivery system for anticancer drugs.

Brief Overview of Various Approaches to Enhance Drug Solubility

Aqueous solubility is one of the most influencing factors when it comes to bioavailability of the drugs. It is the main key for drug effectiveness and enhancing water solubility, which poses one of the greatest challenges in the pharmaceutical industry. Nearly half of newly developed drugs turn out to be insoluble or poorly soluble during initial screening process. Poor solubility limits drug delivery and formulation development. Various techniques have been developed to enhance solubility of poorly soluble drugs. Pharmaceuticals falling under the Biopharmaceutics Classification System (BCS) class II and IV are the main emphasis of this review as these drugs are of low solubility. The methods to improve drug solubility; solid dispersions, cyclodextrin complexation, dendrimers, nano-suspensions, co-solvency, pH adjustment, self-emulsifying drug delivery system, hydrotrophy, cocrystallization and ionic liquid formation are discussed.

Spontaneous bilateral carotid artery dissection and posterior reversible encephalopathy syndrome

Spontaneous bilateral internal carotid artery dissection (sCAD) is rare. About 5 to 10% of carotid artery dissections are bilateral, but they are often revealed by unilateral symptoms, including the following: headache (up to 90%), neck pain (20%), Horner syndrome (50%), pulsatile tinnitus, and cranial nerve palsies (12%).1,2 Dissection may be caused by extrinsic factors, such as trauma or hypertension, or by intrinsic factors, such as primary disease of the arterial wall seen in rare connective tissue disorders such as Ehlers-Danlos or Marfan syndrome.1,3,4,5 However, the etiology of the arterial wall dysfunction that leads to sCAD in the majority of patients is unclear. There is evidence that sCAD may be caused by a transient arteriopathy.4 The development of a transient arteriopathy may make the arterial wall of large and small vessels susceptible to triggering factors for dissection and possibly to arterial wall dysfunction that can be seen in disorders like posterior reversible encephalopathy syndrome (PRES). Clinical manifestations of PRES include headache, decreased alertness, …

Formulation Development and In vitro Evaluation of Oral Extended release Capsules Containing Biodegradable Microspheres

Oral extended-release delivery of Biopharmaceutics Classification System (BCS) class II and III compounds is desirable in order to decrease dosing frequency and potential adverse effects. Maintaining an extended-release profile of the drug is ideal to minimize fluctuations in plasma concentrations. The main objective of this research was to formulate a polymeric microsphere drug delivery system that will effectively provide extended-release characteristics via an orally administered capsule. Using acetaminophen and ibuprofen as model drugs, this drug delivery system was shown to provide extended-release characteristics of the drug for enhanced efficacy. The biodegradable polymeric matrix was formulated using bovine serum albumin (BSA) with glutaraldehyde as the crosslinker. The drug of interest was then encapsulated into the polymeric matrix and spray-dried into microspheres. Once prepared, the drug-loaded microsphere powder was placed into hard gelatin capsules. The physicochemical properties of the microsphere formulations were characterized. Additionally, differential scanning calorimetry was utilized to examine the thermal stability of the encapsulated drug. Release studies were conducted in vitro to examine the release profile of the drug. Cell uptake studies were carried out to examine the internalization capability of microsphere formulations. Drugloaded microspheres were found to be approximately 2 microns in size and exhibited a uniform size distribution. Zeta potential measurements were shown to be approximately -30 mV, which indicated that the microspheres are stable in dispersions. Release data showed a constant release of the drug from the microsphere and capsule formulations for at least 16 hours. Formulated microspheres were able to be internalized into human intestinal Caco-2 cells. These data provided evidence for the role of the microsphere delivery system in the extended-release delivery of BCS Class II and III drug substances.

Multiple Sclerosis: Current and Future Treatment Options

Multiple Sclerosis is an inflammatory and degenerative disorder involving the central nervous system. It primarily affects young adults and may result in significant long-term disability. The most common initial presentation is relapsing remitting, followed by a chronic progressive course. In a small number of patients the disease tends to be progressive from onset. Multiple sclerosis has traditionally been described as a demylinating disorder. There is now overwhelming evidence pointing to a very significant degenerative component. Current treatment options include immunomodulating and immunosuppressive agents as well as monoclonal antibodies and target the inflammatory component of the disease resulting in significant reduction in relapses, decrease in MRI lesion load and a modest effect on disability. There are several other biological agents being developed which target different aspects of the immunopathology of multiple sclerosis. This article will review the agents currently used in the treatment of MS and also discuss agents currently under development.

Rheumatoid Arthritis: A Brief Overview of the Treatment

Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease, affecting the joints with varying severity among patients. The risk factors include age, gender, genetics, and environmental exposure (cigarette smoking, air pollutants, and occupational). Many complications can follow, such as permanent joint damage requiring arthroplasty, rheumatoid vasculitis, and Felty syndrome requiring splenectomy if it remains unaddressed. As there is no cure for RA, the treatment goals are to reduce the pain and stop/slow further damage. Here, we present a brief summary of various past and present treatment modalities to address the complications associated with RA.

Hashimoto Encephalopathy as a Complication of Autoimmune Thyroiditis

Objective: To present a case of Hashimoto encephalopathy as a complication of autoimmune thyroiditis. Clinical Presentation and Intervention: A previously healthy 56-year-old female presented with rapidly progressive cognitive decline and visual hallucinations. Being a diagnosis of exclusion, Hashimoto encephalopathy required an extensive laboratory and diagnostic workup, which was done over the course of a 15-day hospitalization. The patient recovered after initial treatment with intravenous methylprednisolone and was then switched to prednisone p.o. Conclusion: This case report illustrates the importance of awareness for Hashimoto encephalopathy, as it remains one of the few easily treatable and reversible causes of rapid cognitive decline.

Disease Modifying Agents in the Treatment of Multiple Sclerosis

Numerous agents have been tested in multiple sclerosis and the vast majority of these have either failed to show a beneficial effect or produced undesirable side effects. In some cases, there was worsening of disease activity. Treatment strategies for multiple sclerosis over the last 16 years have undergone a profound change. Several treatment options are now available primarily targeting the inflammatory phase of the disease [clinically isolated syndrome (CIS), relapsing remitting multiple sclerosis (RRMS), and secondary progressive multiple sclerosis (SPMS) with relapses]. All currently approved disease-modifying agents (DMA) are moderately effective in reducing relapses and MRI activity. The treatment effect appears to be greater when these drugs are used soon after onset of symptoms. The effect on long-term disability seems to be modest if any. This chapter reviews both currently used agents (both FDA approved and off-label) and also discusses several promising agents in various phases of development.

Is Multiple Sclerosis a Vascular Disease

Multiple sclerosis (MS) is widely recognized as a progressive, inflammatory neurogenerative disease, for which the causative agent(s) or triggers are not well known. A recent hypothesis is that MS is caused, at least to some extent, by chronic venous insufficiency of the extracranial venous drainage. In this chapter, we explore the historical and modern perspectives on possible vascular etiologies to multiple sclerosis, parallels from other cerebrovascular diseases, and identify future areas of exploration.

Infections of the Central Nervous System

Infections of the central nervous system (CNS) may be acute (days) or chronic (months to years). The CNS is sequestered from the rest of the body. The blood brain barrier (BBB) excludes most microorganisms and also vital immune cells including phagocytes, antibodies, and complement. Once this barrier is breached, pathogens in the subarachnoid space may grow logarithmically. In this chapter, we discuss the immune response and clinical manifestations of common bacterial, viral, fungal, and parasitic infections of the CNS.