Current Drug Delivery - Volume 3, Issue 4, 2006

The aim of this study was to evaluate the effect of different grades of poly D, L lactide-co-glycolide (PLGA) on the properties of microspheres encapsulated with Cyclosporine A (CyA). Microspheres were prepared by solvent evaporation method using three grades of PLGA. Various characteristics of microspheres such as morphology, size distribution, encapsulation efficiency and release profile were evaluated. Complementary studies were also carried out by Infrared (IR) spectroscopy and Differential scanning calorimetry (DSC) to evaluate possible drug-polymer interactions. Scanning electron microscopy (SEM) studies showed microspheres as spherical particles with CyA deposited as islands on the surface of spheres. Particle size range was 1-25 mm for microspheres made of PLGA (50:50) which showed the minimum size. Encapsulation efficiency was found to vary from 75% to 92% in various formulations. The profile of release was biphasic, showing an initial rapid phase followed by a continuous and slower rate thereafter. Microspheres made of grades 50:50 and 85:15 showed the highest and lowest amount of drug release, respectively. IR spectra for drug, polymer and microspheres did not indicate any chemical interaction between the components of microsphere and DSC thermograms revealed that CyA was present in its amorphous state within microspheres. In conclusion, the effect of polymer characteristics should be considered in microsphere formulations. In this study, suitable microspheres especially with PLGA (50:50) were prepared which allow the controlled release of CyA over a prolonged period of time.

A photocrosslinkable chitosan (Az-CH-LA) aqueous solution resulted in an insoluble hydrogel like a soft rubber within 30 sec of ultraviolet light (UV)-irradiation. The photocrosslinked chitosan hydrogel showed strong sealing strength and potential use as a new tissue adhesive in surgical application. Paclitaxel, which is an anti-tumor reagent and a vascularization-inhibitor, retained in the photocrosslinked chitosan hydrogel, and were gradually released from the photocrosslinked chitosan hydrogel in vivo upon the degradation of the hydrogel. The paclitaxel-incorporated photocrosslinked chitosan hydrogels effectively inhibited tumor growth and angiogenesis in mice. On the other hand, the fibroblast growth factor (FGF)-2 molecules also retained in both the photocrosslinked chitosan and an injectable chitosan/ IO4-heparin hydrogels, and were gradually released from the hydrogels upon their in vivo biodegradations. The activity of FGF-2 in the hydrogels was stable for long time (more than 14 days). The controlled release of biologically active FGF-2 molecules from the hydrogels caused an induction of the angiogenesis and, possibly, collateral circulation occurred in the healing-impaired diabetic (db/db) mice and the ischemic limbs of rats. The purpose of this review is to describe the effectiveness of the chitosan hydrogels (photocrosslinkable chitosan hydrogel and chitosan/IO4-heparin hydrogel) as a local drug delivery carrier for FGF-2 and paclitaxel to control wound repair, tumor growth, and angiogenesis. It is thus proposed that the chitosan hydrogels may be a promising new local carrier for drugs such as FGF-2 and paclitaxel.

Brucellosis is a highly contagious bacterial zoonosis that affects millions of people worldwide. Brucella is highly infectious, especially when aerosolized. The infection induces severe protracted diseases, which are both debilitating and incapacitating, hence, Brucella melitensis has been considered a potential biological warfare agent. In the battle against Brucella, it is crucial to know its chemical-structure and biochemistry-metabolic characteristics. It is well known that Brucella, as well as many other intracellular bacterial pathogens, has evolved to survive and even proliferate within monocytes and macrophages cells. Depending on the route of entry (complement, Fc, lectin or fibronectin receptors), the fate of the bacteria will vary; it may even segregate from the endocytic route towards the endoplasmic reticulum. This intracellular “non regular” behaviour of Brucella makes treatment difficult. Most antibiotics, although effective in vitro, do not actively pass through cellular membranes, or, once inside, may not reach the discrete intracellular niche where the bacteria is hidden. Therefore, complete eradication of the microorganisms is difficult to achieve, and the incidence of relapses is rather high. Taking these data into consideration, this review will evaluate the past, current and new trends in the control of brucellosis, paying special attention to the drug delivery systems as potential vectors for targeting these intracellular sites where the organisms are located.

The objective of the present investigation was to prepare and evaluate floating granular delivery system consisting of (i) calcium silicate (CS) as porous carrier; (ii) ranitidine hydrochloride (RH), an anti-ulcer agent; and (iii) hydroxypropyl methylcellulose K4M (HPMC) and ethylcellulose (EC) as matrix forming polymers. The effect of various formulation and process variables on the particle morphology, particle size, micromeritic properties, percent drug content, in vitro floating behavior, and in vitro drug release from the floating granules was studied. The scanning electron microscopy (SEM) of granules revealed that that more pores of CS in secondary coated granules (SCG) were covered by the polymer film than those in primary coated granules (PCG). The formulation demonstrated favorable in vitro floating and drug release characteristics. The in vivo evaluation for the determination of pharmacokinetic parameters was performed in albino rats. Higher plasma concentration was maintained throughout the study period from the floating granules of RH. The enhanced bioavailability and elimination half-life observed in the present study may be due to the floating nature of the dosage form. The results suggested that CS is a useful carrier for the development of floating and sustained release preparations.

The aim of this study was to investigate how the delivery rate of erodible sustained-release hydrophilic matrices intended for the delivery of poorly soluble drugs can be optimized through the incorporation of drug/cyclodextrin binary systems. Carvedilol (CAR), a sparingly water-soluble antihypertensive drug, was selected as a model for the study. As first, we attempted to improve CAR apparent solubility by association with hydroxypropyl-β-cyclodextrin (HPβCD) and then incorporated CAR/HPβCD binary systems in sustained-release tablets made of poly(ethyleneoxide) (PEO). Solid CAR/HPβCD binary systems were prepared by physical mixing, kneading, co-melting and freeze-drying methods and characterized by DSC and X-ray powder diffractometry. The amount of CAR dissolved from all the HPβCD-containing systems was higher than pure CAR, the co-molten and freeze-dried products showing the best dissolution performance. The incorporation of the binary systems in PEO tablets resulted in a CAR release rate much higher than tablets containing only CAR. It was found that the time necessary to achieve complete release from the tablet was linearly related to the dissolution parameters of CAR/HPβCD powders. In the case of co-molten and freeze-dried products, all CAR content could be released in about 12 and 10 h, respectively. Our results demonstrate that the incorporation of drug/cyclodextrin solid systems in erodable PEO matrices intended for the delivery of poorly water-soluble drugs is useful to modulate the release rate by controlling the dissolution properties of the drug inside the tablet.

The most common feature for antigen-delivery systems is their particulate nature. Together with a certain depot effect, it is the particulate nature that primarily dictates whether the antigen-delivery system will be successful in inducing a certain type and strength of immune response. In this article, we will summarize recent data on particulate delivery systems for peptide and protein antigens with a main focus on lipid or polymer-based particles, all of which possess high potential as both preventive and therapeutic vaccines for parenteral, nasal, and possibly oral administration.

ISCOMs have received much attention as vaccine adjuvants due to their immunostimulatory effects. They are colloidal particles typically comprised of phospholipids, cholesterol and Quil A, a crude mixture of saponins extracted from the bark of Quillaja saponaria Molina. We have previously shown that ISCOMs can be prepared by ether injection wherein an ether solution of phospholipids and cholesterol in a mass ratio of 5:2 is injected into a solution of Quil A at a mass ratio of 7 lipids: 3 Quil A. The aim of this study was firstly to isolate and characterise discrete fractions of Quil A and secondly to investigate which of these fractions were able to form ISCOMs by the method of ether injection. Six fractions of Quil A were isolated by semi-preparative reverse phase high performance liquid chromatography (RP-HPLC) and characterised by analytical HPLC, liquid chromatography tandem mass spectrometry (LC-MS) and the qualitative Liebermann- Burchard and Molisch tests for triterpenoids and carbohydrates respectively. ISCOMs were subsequently prepared from the isolated fractions by the method of ether injection and the resulting preparations characterized by photon correlation spectroscopy (PCS) and negative stain transmission electron microscopy (TEM). The molecular weights of the major compounds in the fractions ranged from ∼1200 to ∼2300 Da; all fractions tested positive for triterpenoids and saccharides and four of the fractions were identified as QS-7, QS-17, QS-18 and QS-21 by analysis (LC-MS and analytical HPLC). Injection of ether solutions of lipids into aqueous solutions of QS-17, QS-18 or QS-21 all resulted in homogeneous ISCOM dispersions. The combination of lipids and QS-7 by ether injection produced lamellae and liposomes as the prominent structures and a minor amount of ISCOMs. The remaining two hydrophilic, low molecular weight fractions of Quil A did not produce ISCOMs, instead liposomes and helical structures predominated in the samples.

OBJECTIVE: Isolation of the total saponins from Acanthophyllum squarrosum Boiss. and investigation of its surface activity, haemolytic effects on human erythrocytes as well as enhancing potentials on intranasal insulin absorption in rat in comparison with two other enhancers i.e. Quillaja total saponin (QTS) and sodium cholate (SC). MATERIALS AND METHODS: The decrease in blood glucose levels in five fasting rats following nasal administration of regular insulin solutions in the presence or absence of enhancers was determined by glucometric strips and used as an indication of insulin absorption. RESULTS: The results showed that ATS decreased surface tension of water to about 50 dyne.cm-1 and caused complete haemolysis of human RBCs at a concentration of 250 μg.ml-1. Following the instillation of solutions containing insulin and different absorption enhancers into the right nostril of rats, the percentage decrease in initial blood glucose was as follows: 72.46% (± 2.39%) for ATS, 63.22 % (± 11.06%) for QTS and 60.06% (± 14.93%) for SC. Percentage lowering in initial blood glucose concentrations against time showed that ATS exhibits a stronger effect than the two other enhancers although the difference was not statistically significant (p>0.05). CONCLUSION: ATS has a considerable absorption enhancing effect and can possibly be used to increase insulin bioavailability via nasal route. However the potential toxic effects of this saponin on nasal mucosa should be further evaluated.

The formulation of sunscreens products requires information about the properties of the substances responsible for the sun protection, their action mechanisms and the vehicles used for their administration. The improvement of the performance of sunscreen substances by a modification of their chemical, physical and technological properties or by the use of conventional and novel carriers is described in this review. The sun protection achieved by the use of sunscreens incorporated into carriers in terms of the sun protection factor (SPF) and other performance indices is also shown. Current manufacturing methods to incorporate sunscreen substances into vehicles are briefly described. Furthermore, basic information related to the dermatological effects of the UV radiation classified according to the different spectral regions of the UV radiation is presented in this manuscript.

The purpose of this research is to evaluate the suitability of lecithin organogels containing aceclofenac for topical application. The present article focuses on the preformulation part of the whole research work. Thin layer chromatography was carried out to determine lecithin's purity. The excipients for formulating lecithin organogel were screened. Lecithin organogels are thermo reversible in nature and hence gelation temperature study was carried out to determine the temperature where Sol-Gel and Gel-Sol transformation takes place. Partition coefficient of the drug was estimated. Drug solubility in plain oil and organogel containing reverse micelles was estimated. Effect of water added on the properties of lecithin organogels such as X-ray diffraction pattern, conductivity and viscosity were determined. Microscopy of the gel sample has been carried out at different magnifications. The pseudo ternary phase diagram has been constructed to determine the organogel existence region. The permeation study of aceclofenac from different concentrations of lecithin organogels [200mM, 300mM and 400mM] has been determined using cellulose acetate membrane (0.45μ) and excised rat skin. Lecithin organogel in ethyl oleate has desired stability and consistency. A single spot on the TLC plate confirms the purity of soy lecithin to be used in organogel formation .Aceclofenac solubility was found to be more in lecithin/oil reverse micellar system as compared to its solubility in oil. The X-ray diffraction pattern confirms the incorporation of water in micellar gel network. The physical properties of organogels are affected by water incorporated and concentration of gelator.The permeation of aceclofenac through artificial membrane and excised rat skin demonstrated the same trend and were in the following order 200mM>300mM>400mM.The results showed that organogel exhibits useful pharmaceutical properties.

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.