Current Drug Delivery (v.9, #6)

Alginate based Hydrogel as a Potential Biopolymeric Carrier for Drug Delivery and Cell Delivery Systems: Present Status and Applications by Tapan Kumar Giri, Deepa Thakur, Amit Alexander, Ajazuddin, Hemant Badwaik, Dulal Krishna Tripathi (539-555).
Alginate is a non-toxic, biocompatible and biodegradable natural polymer with a number of peculiar physicochemical properties for which it has wide applications in drug delivery and cell delivery systems. Hydrogel formation can be obtained by interactions of anionic alginates with multivalent inorganic cations by simple ionotropic gelation method. Hydrophilic polymeric network of three dimensional cross linked structures of hydrogels absorb substantial amount of water or biological fluids. Among the numerous biomaterials used for hydrogel formation alginate has been and will continue to be one of the most important biomaterial. Therefore, in view of the vast literature support, we focus in this review on alginate - based hydrogel as drug delivery and cell delivery carriers for biomedical applications. Various properties of alginates, their hydrogels and also various techniques used for preparing alginate hydrogels have been reviewed.

Anatomical, Biochemical and Physiological Considerations of the Colon in Design and Development of Novel Drug Delivery Systems by Harini Chowdary Vadlamudi, Y. Prasanna Raju, B. Rubia Yasmeen, Jayasri Vulava (556-565).
The colon is composed of four distinct layers such as serosa, muscularis externa, sub mucosa and mucosa. There exists a difference in the anatomy, neural and blood supply and absorption characteristics as the length of the colon is traversed. At birth the mucosal surface of the colon is similar to that of the small intestine but rapid changes occur with the loss of the villi leaving flat mucosa with deep crypts. The existence of receptors like muscarinic M3, cholecystokinin1, Eph, Erb B, estrogen (α, β), gastrin releasing peptide, killer Ig like receptor, lymphocyte-endothelial receptor, notch, pregnane X, substance P and peroxisome proliferator-activated γ receptor can be utilized as a promising approach for targeting. The inner compact firm mucus is impervious to bacteria, making it a defensive barrier for the colossal bacterial load. The mucus thus provides innate immunity to maintain the homeostasis in colon. The physiological properties of the colon such as pH, transit time, luminal pressure of the colon, and the presence of microbial flora localized in the colon are utilized in the drug design. The drug delivery systems exploit enteric coating and biodegradable polymers to reach colon in an intact form by surpassing the barriers in the stomach and small intestine. The presence of azo-reductase, glucuronidase, dextranase, pectinase, glycosidase, polysaccharidase made it feasible to design prodrug and enzyme based drug delivery. Drug designing methodologies in colon specific drug delivery include pH- based systems, enzymedepended systems, timed- release systems and pressure/osmotically release systems.

The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine delivery as well as the development of new devices. The surface area of the nasal cavity is about 160 cm2, or 96 m2 if the microvilli are included. The olfactory region, however, is only about 5 cm2 (0.3 m2 including the microvilli). There are 6 arterial branches that serve the nasal cavity, making this region a very attractive route for drug administration. The blood flow into the nasal region is slightly more than reabsorbed back into the nasal veins, but the excess will drain into the lymph vessels, making this region a very attractive route for vaccine delivery. Many of the side effects seen following intranasal administration are caused by some of the 6 nerves that serve the nasal cavity. The 5th cranial nerve (trigeminus nerve) is responsible for sensing pain and irritation following nasal administration but the 7th cranial nerve (facial nerve) will respond to such irritation by stimulating glands and cause facial expressions in the subject. The first cranial nerve (olfactory nerve), however, is the target when direct absorption into the brain is the goal, since this is the only site in our body where the central nervous system is directly expressed on the mucosal surface. The nasal mucosa contains 7 cell types and 4 types of glands. Four types of cells and 2 types of glands are located in the respiratory region but 6 cell types and 2 types of glands are found in the olfactory region.

The bone infections are the most divesting complications confronted by the physicians and patients. The antibiotic loaded bone cements, such as synthetic ceramics and natural ceramics were accepted for bone infections. The currently available bone cements were not accepted due to the lack of mechanical strength, porosity and quick degradation rate etc. The major aim of this review is to discuss about several different synthetic methods used to prepare the bioactive diopside (CaMgSi2O6) and its applications in ceramic drug delivery systems for controlled and targeted delivery. It has been reported from various research articles, diopside was mainly used for bone tissue regeneration, dentistry, orthopedics and enzyme delivery matrices with different formulations. Compared to other bioceramics diopside is preferable due to its biocompatibility and high mechanical strength.

The use of polymers and their microspheres in drug delivery is well known for they are being widely used in the field of drug delivery. The polymer entraps a drug which is to be released in a predesigned manner in the body through biodegradation. The blending of polymers is one way of modifying and enhancing the properties of polymer- based products which is also a cost effective procedure rather than developing a new product. The molecular weight of the polymer, the composition of the blend, the sphere porosity and size, and drug distribution are found to be controllable factors on which drug delivery depends. Polymer blends are obtained by allowing two polymers to combine as one material which has the advantage of two or more polymers. Polymer microspheres are small spherical particles with diameters in the micrometer range between 1μm to 1000μm which are manufactured from various natural and synthetic materials. Microspheres are used to administer medication in a rate- controlled manner and sometimes in a targeted manner. This review presents various polymer blend- combinations in different ratios, the different processing techniques adopted and the details of their characterization through examples found in a literature survey. The characterization of the different polymer blends or microspheres showed changes in structure, increase in drug loading, encapsulation efficiency, biocompatibility and low cytotoxicity.

The study was undertaken to develop buffered nanoemulsion of ziprasidone hydrochloride (fifth generation antipshychotic) and evaluate its potential for efficacious nose to brain delivery drug delivery in animal models. Homogeneous buffered ziprasidone nanoemulsions (BZNE) were prepared by aqueous (phosphate buffer, pH 8.0) titration method using capmul MCM, labrasol and transcutol as oil, surfactant and cosurfactant respectively. The NEs (F1-F7) were characterized for pharmaceutical characteristics (% transmittance, PDI value, Zeta potential, globule size, viscosity and diffusion coefficient) and F6 with mean globule size of 145.24 ± 4.75nm (PDI = 0.186 ± 0.40) and diffusion coefficient of 0.1901± 0.04cm2/min was thermodynamically stable and was developed as buffered mucoadhesive nanoemulsions. The buffered mucoadhesive NE (βmax = 0.57) that contained 0.5% by weight of chitosan (BZMNE) exhibited 1.79 times higher diffusion coefficient (0.3418 ± 0.03) than BZNE. Pharmacodynamic study confirmed the superiority of BZMNE over BZNE in locomotor activity test (p < 0.05) and paw test (p < 0.05). Nasal ciliotoxicity study revealed the optimized BZMNE to be free from acute toxicity. Conclusively, a stable and efficacious buffered mucoadhesive NE of ziprasidone hydrochloride, that can be safely administered by intranasal route was developed.

Objective: Present work focuses on the use of tamarind gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. Method: The desired aim was achieved by fabricating a floating delivery system bearing time – lagged coating of Tamarindus indica seed polymer for the programmed release of Famotidine. Response Surface Methodology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 32 full factorial design was used in designing the experiment. % weight ratio of tamarind gum to ethyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time for drug release and the cumulative % drug release in 330 minutes were the observed responses. Key findings: Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. Conclusion: The optimized formulation prepared according to the computer generated software, Design-Expert® deciphered response which were in close proximity with the experimental responses, thus confirming the robustness and accuracy of the predicted model for the utilization of natural polymer like tamarind gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

Permeation of PLGA Nanoparticles Across Different in vitro Models by Lindiwe A. Nkabinde, Lungile N.N. Shoba-Zikhali, Boitumelo Semete-Makokotlela, Lonji Kalombo, Hulda S. Swai, Rose Hayeshi, Brendon Naicker, Thembela K. Hillie, Josias H. Hamman (617-627).
Many drug delivery systems have indicated improvement in delivery of various drug molecules and among these biodegradable and biocompatible polymers such as poly(D,L-lactide-co-glycolide) (PLGA) have been shown to enhance intracellular uptake of drug candidates when formulated as nanoparticles. PLGA nanoparticles were prepared by means of a double emulsion solvent evaporation technique and evaluated in terms of size, encapsulation efficiency, surface charge, isoniazid release and in vitro transport. The nanoparticles have an average size of 237 nm and were previously shown to be distributed in several tissues after oral administration without triggering an immune response. This study focussed on the in vitro permeation of the PLGA nanoparticles across different membranes and showed that although Rhodamine 6G-labelled nanoparticles are efficiently delivered across the intestinal epithelium, its epithelial permeability changes when a drug such as isoniazid is encapsulated. Future studies should focus on ways to optimise PLGA nanoparticle delivery when a drug such as isoniazid is encapsulated for instance by coating with polymers such as polyethylene glycol.

Synthesis and Characterization of Carboxymethyl Chitosan Hydrogel: Application as pH-Sensitive Delivery for Nateglinide by Subhash S. Vaghani, Madhabhai M. Patel, C. S. Satish, Kandarp M. Patel, Nurudin P. Jivani (628-636).
In current research, chitosan was reacted with mono-chloroacetic acid under alkaline condition to prepare carboxymethyl chitosan (CMCTs). The degree of substitution (Ds) on prepared CMCTs was found to be 0.68. CMCTs was used as a potential carrier for pH specific delivery of nateglinide after crosslinked using glutaraldehyde in presence of nateglinide. The average molecular weight and degree of deacetylation (DD) of chitosan were found to be 3.5x104 Da and 84.6% respectively. High yield (82%) and loading of drug (75%) were found in the developed hydrogel formulations. pH responsive swelling behavior of prepared hydrogels was checked using different pH values (1.2, 6.8 and 7.4). The study indicated very less swelling at pH 1.2 (for first 2 h) and quick swelling at pH 6.8 (for next 3 h) followed by linear swelling at pH 7.4 (for next 7 h) with slight increase. In vitro release profile of hydrogels showed biphasic release pattern dependent on swelling behavior. The release pattern was found to be non-fickian diffusion kinetics at higher pH. FTIR, 1H-NMR, DSC and p-XRD studies were carried out to confirm the formation of CMCTs, drug entrapment and its possible interaction in formulations. These studies revealed that no chemical change was found in nateglinide during preparation of hydrogel formulations. Scanning Electron Microscopy (SEM) was used to study the surface morphology of prepared hydrogels before and after dissolution which revealed pores formation after dissolution.

A Rational Design for the Nanoencapsulation of Poisonous Animal Venoms in Liposomes Prepared with Natural Phospholipids by Maria Helena Bueno da Costa, Osvaldo A. Sant'Anna, Wagner Quintilio, Reto Albert Schwendener, Pedro Soares de Araujo (637-644).
Liposomes have been used since the 1970's to encapsulate drugs envisaging enhancement in efficacy and therapeutic index, avoidance of side effects and increase in the encapsulated agent stability. The major problem when encapsulating snake venoms is the liposomal membrane instability caused by venom phospholipases. Here the results obtained encapsulating Crotalus durissimus terrificus and a pool of Bothropic venoms within liposomes (LC and LB, respectively) used to produce anti-venom sera are presented. The strategy was to modify the immunization protocol to enhance antibody production and to minimize toxic effects by encapsulating inactivated venoms within stabilized liposomes. Chemically modified venoms were solubilized in a buffer containing an inhibitor and a chelating agent. The structures of the venoms were analyzed by UV, CD spectroscopy and ELISA. In spite of the differences in the helical content between natural and modified venoms, they were recognized by horse anti-sera. To maintain long-term stability, mannitol was used as a cryoprotectant. The encapsulation efficiencies were 59 % (LB) and 99 % (LC), as followed by filtration on Sephacryl S1000. Light scattering measurements led us to conclude that both, LB (119 ±47 nm) and LC (147±56 nm) were stable for 22 days at 4 oC, even after lyophilization. Genetically selected mice and mixed breed horses were immunized with these formulations. The animals did not show clinical symptoms of venom toxicity. Both, LB and LC enhanced by at least 30 % the antibody titers 25 days after injection and total IgG titers remained high 91 days after immunization. The liposomal formulation clearly exhibited adjuvant properties.