Current Drug Delivery - Volume 12, Issue 3, 2015

Long acting parenteral formulations are preferred over conventional formulations for the treatment of chronic diseases. Prevalence of such diseases provoked the interest of researchers and pharmaceutical industries in the development of long acting parenteral formulations. The regulatory guidelines and pharmacopoeia have remained silent on dissolution methods for long acting parenteral formulations due to their diverse nature. The lack of compendial method for dissolution testing increases the duration of approval process for long acting parenteral formulations. This article reviews various dissolution methods used to study in vitro drug release profile of long acting parenteral formulations. Compendial as well as noncompendial methods, such as- rotating dialysis cell, dialysis tube, rotating bottle, shaking flask, single drop, inverted cup and incubation, are used by researchers for drug release profile of long acting parenteral formulations. This review article also highlights the advantages and disadvantages of reported dissolution methods along with the suitability of these methods for particular type of long acting formulation. The compiled work will help the researchers in designing the biorelevant dissolution method and expedite the development of long acting parenteral formulations.

A palpable need for the optimization of therapeutic agents, due to challenges tackled by them such as poor pharmacokinetics and chemoresistance, has steered the journey towards novel interdisciplinary scientific field for emergence of nanostructure materials as a carrier for targeted delivery of therapeutic agents. Amongst various nanostructures, nanodiamonds are rapidly rising as promising nanostructures that are suited especially for various biomedical and imaging applications. Advantage of being biocompatible and ease of surface functionalization for targeting purpose, besides safety which are vacant by nanodiamonds made them a striking nanotool compared to other nonmaterials which seldom offer advantages of both functionality as well as safety. This review outlines the summary of nanodiamonds, regarding their types, methods of preparation, and surface modification. It also portrays the potential applications of nanodiamond as targeted drug delivery of various bioactive agents. Based on photoluminescent and optical property, nanodiamonds are envisioned as an efficient bioimaging nanostructure. Nanodiamonds as a novel platform hold great promise for targeting cancer cells and in-vivo cell imaging. Based upon their inimitable properties and applications nanodiamonds propose an exciting future in field of therapeutics and thus possess vibrant opportunities.

This review highlights recent interests and applications of disulphide and thiol chemistry in creating contemporary macromolecular designs. Due to the chemical nature of disulphides and thiols a wide range of chemical species react with these functional groups to yield a variety of polymers extending their applications in chemical, biological, physical, material engineering and material sciences. The review aims to illustrate the versatility and demonstrate the potential of thiol-based chemistries. The focus is on exploring bio-cleavable disulphides and linking by “clicking” thiols via thiol/other functional group exchange reactions. Thiol synthesis, modification and functionalization are demonstrated to be highly attractive and efficient in polymer and material science which in turn have immense application in biological therapeutics and drug delivery. The review also illustrates the remarkable pliability of synthetic and natural approaches to designing, optimizing and functionalizing nanostructures and conjugates by thiol chermistry modification. The examples quoted in the review illustrate the power and versatility of thiols for site specific functionalization, the construction of complex macromolecules and the generation of both biodegradable disulphides and non-biodegradable bonds which are the tools for constructing specific therapeutic/drug delivery systems. In addition, the ability of thiols to react with various functional groups found in a variety of polymer science materials and biological entities such as peptide and related structures will also be demonstrated. Despite of the fact that research efforts in thiol chemistry are still at the early stages, it is likely that its true potential will be developed.

The aim of the study was to develop and evaluate Polyelectrolyte complex (PEC) microparticles composing Lactobacillus Acidophilus (probiotic) and Fructo oligosaccharide-Lactobacillus Acidophilus (prebiotic-probiotic), for sustaining and enhancing intestinal growth of probiotic bacteria. Gum Karaya-Chitosan(GK-CH) was used to fabricate PEC microparticles by extrusion method. The prepared microparticles were characterized for FT-IR, DSC and particle size and evaluated for percentage yield, swelling, surface morphology, entrapment rate and further studied for influence of prebiotic over probiotic growth. The fabricated PEC microparticles composed of Probiotic and Prebiotic- Probiotic have exhibited sustainability of probiotic bacteria for 12 hrs in GIT conditions and presence of prebiotic in the preparation enhanced the probiotic cell growth. Hence, it can be concluded that PEC between GK-CH was found to be successful in sustaining cell release and presence of prebiotic was found to enhance the probiotic cell growth.

Fenofibrate is virtually insoluble in water and is highly lipophilic, which leads to poor oral bioavailability. The purpose of this approach is to develop self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of fenofibrate. The in vitro dissolution test and pharmacokinetic behavior in beagle dogs were conducted to assess the formulation of fenofibrate in selfmicroemulsifying systems. The concentrations of fenofibrate were determined by HPLC. A crossover fashion study was performed in six fasted beagle dogs with SMEDDS formulation and commercial capsules. The results showed that SMEDDS formulation provides a good drug release with more than 90% of fenofibrate dissoluted from self-emulsifying formulations while less than 10% from the commercial capsules was released within 20min. The mean particle size of SMEDDS formulation after dispersion was about 33.7nm In pharmacokinetic parameters of SMEDDS formulation, the area under the plasma concentration-time curve (AUC) was significantly higher and was approximately 7-fold greater than that obtained when commercial capsule of the same dose of fenofibrate was administered. Also, the maximum absorption was advanced (2h to 1.25h) with SMEDDS formulation. The self-microemulsifying drug delivery systems can significantly increase fenofibrate dissolution in vitro and absorption in vivo.

Simvastatin potassium is a hypolipidemic drug used with exercise, diet, and weight-loss to control elevated cholesterol, or hypercholesterolemia. It is a member of the statin class of pharmaceuticals. Okra mucilage is used to reduce the cholesterol level since microspheres has formulated by using okra mucilage to developed a synergistic effect. Calcium chloride act as a cross linking agent, when react with sodium alginate form a calcium alginate, since develope a gel like microbeads (microspheres). The half life of simvastatin is 2h for simvastatin acid. Simvastatin microspheres were prepared by using sodium alginate in combination with Abelmoschus esculentus (Okra), as drug release modifiers in various proportions to overcome the drug related adverse effects. The drug entrapment efficiency increased progressively with increasing concentration of both sodium alginate and okra mucilage resulting in the formation of larger microspheres entrapping greater amounts of the drug. The prepared microspheres were subjected to various evaluation and in vitro release studies. The particle sizes of the prepared microspheres were determined by optical microscopy and Scanning Electron Microscopy (SEM) analysis. The prepared microspheres had good spherical geometry with smooth surface as evidence by SEM. Study the capability of the formulation to withstand the physiological environment of the stomach and small intestine.

The objective of the present research was to cultivate an oral formulation of an anti-diabetic drug using polymeric nanofiber. A biodegradable polymer i.e. poly (vinyl alcohol) (PVA) nanofiber loaded linagliptin was prepared using electro spinning technique. The drug entrapment in the developed nanofibers was confirmed by scanning electron microscopy and X-ray diffraction. The in vivo study was performed on male Wistar rats to establish the pharmacodynamics behavior of developed formulation. The mucoadhesive strength results confirmed that the drug loaded PVA nanofiber patch had the highest mucoadhesion strength compare to PVA film and blank PVA nanofiber, due to its higher water holding capacity and surface area. The in vitro release study suggested that controlled release array of the drug from the nanofiber patch. In vivo activity validated the fact that linagliptin was delivered in its active state and showed visible results when compared to the commercial formulation. Additionally an encapsulation efficacy of 92% of the experimental formulation provides sufficient suggestion that the nanofibers serve as an ideal carrier for the delivery of linagliptin via the sublingual route.

Substantial amount of research has been done in recent decades for the development of nanoparticle systems to selectively deliver drugs to cancer cells for concurrently enhancing and reducing anti-cancer and off-target effects, respectively. pH-sensitive carbonate apatite (CA) was originally developed for efficient and targeted delivery of DNA, siRNA and proteins to various cancer cell lines. Recently, the CA particles were employed to deliver anti-cancer drugs, cyclophosphamide, doxorubicin and methotrexate to cancer cells. Here, we report on the fabrication and characterization of gemcitabine- loaded CA particles, followed by the evaluation of their roles in enhancement of cytotoxicity in two human and one murine breast cancer cell lines. HPLC was performed to measure binding efficiency of the drug to the apatite particles whereas particle size and zeta potential were evaluated to characterize drug/apatite complex. Depending on the initial doses of the drug, its bind binding affinity towards the particles varied from 3.85% to 4.45%. The particle size was found to surprisingly decrease with an increase of the initial drug concentration. In vitro chemosensitivity assay revealed that apatite/drug nanoparticle complexes presented significantly higher cytotoxicity to breast cancer cells compared to free drugs, which could be correlated with the enhanced cellular uptake of the small size drug-loaded particles through endocytosis compared to the passive diffusion of the free drug.

The aim of this study was to investigate the use of tomatine adjuvant to deliver soluble antigen for crosspresentation by bone marrow-derived dendritic cells (BMDCs). BMDCs were incubated with tomatine adjuvantovalbumin (OVA) complex and analyzed for antigen uptake by flow cytometry. Adjuvant-induced cell death was examined in situ by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. To elucidate the effect of antigen internalization on tomatine adjuvant-mediated antigen presentation, BMDCs were treated with several endocytosis inhibitors, and antigen presentation was analyzed by B3Z activity assay. Our data indicated that tomatine adjuvant enhanced antigen internalization by antigen presenting cells (APCs) and induced significant cell death and leukocyte infiltration at the injection sites. In vitro tomatine adjuvant treatment of BMDCs activated Ova/Kb restricted B3Z T cell hybridomas, whereas this activation was impaired by pretreatment with brefeldin A, cytochalasin B, wortmannin, or ZnCl2. Our results demonstrated the role of tomatine adjuvant in antigen delivery to antigen presenting cells (APCs) and suggested the involvement of phagocytosis and PI3K signaling during the delivery of soluble antigens in the context of MHC class I.

The objective of this research project was to develop a nanoparticle drug delivery system using the biopolymer chitosan as the base component. The nanoparticles were produced through ionotropic gelation by flush mixing chitosan with counterions carrageenan and alginate. The nanoparticles were generated under a range of conditions to determine the effect of pH, chitosan concentration, carrageenan concentration, and alginate concentration on the nanoparticle characteristics of particle diameter, zeta potential, and particle size distribution. The encapsulation and controlled release of BSA from chitosan nanoparticles was also evaluated. The encapsulation of BSA was used as a model system for the controlled drug delivery from composite nanoparticles. The release profile indicated an initial burst in the first few hours of the trial, followed by a slower steady release over time. According to Korsmeyer-Peppas model, the release profile followed fickian diffusion.