Site-specific Delivery Systems Research Articles

ChemInform Abstract: Hyperbranched Polyphosphates: Synthesis, Functionalization and Biomedical Applications

AbstractReview: 50 refs.

Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids

BackgroundLow levels of HDL-C are an independent cardiovascular risk factor associated with increased premature cardiovascular death. However, HDL-C therapies historically have been limited by issues relating to immunogenicity, hepatotoxicity and scalability, and have been ineffective in clinical trials. ObjectiveWe examined the feasibility of using injectable acoustic microspheres to locally deliver human ApoA-I DNA plasmids in a pre-clinical model and quantify increased production of HDL-C in vivo. MethodsOur novel site-specific gene delivery system was examined in naïve rat model and comprised the following steps: (1) intravenous co-administration of a solution containing acoustically active microspheres (Optison™, GE Healthcare, Princeton, New Jersey) and human ApoA-I plasmids; (2) ultrasound verification of the presence of the microspheres within the liver vasculature; (3) External application of locally-directed acoustic energy, (4) induction of microsphere disruption and in situ sonoporation; (4) ApoA-I plasmid hepatic uptake; (5) transcription and expression of human ApoA-I protein; and (6) elevation of serum HDL-C. ResultsCo-administration of ApoA-I plasmids and acoustic microspheres, activated by external ultrasound energy, resulted in transcription and production of human ApoA-I protein and elevated serum HDL-C in rats (up to 61%; p-value < 0.05). ConclusionsHDL-C was increased in rats following ultrasound directed delivery of human ApoA-I plasmids by microsphere sonoporation. The present method provides a novel approach to promote ApoA-I synthesis and nascent HDL-C elevation, potentially permitting the use of a minimally-invasive ultrasound-based, gene delivery system for treating individuals with low HDL-C.

Light-stimulated cargo release from a core–shell structured nanocomposite for site-specific delivery

This paper reported a core–shell structured site-specific delivery system with a light switch triggered by low energy light (λ=510nm). Its core was composed of supermagnetic Fe3O4 nanoparticles for magnetic guiding and targeting. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which offered highly ordered hexagonal tunnels for cargo capacity. A light switch N1-(4aH-cyclopenta[1,2-b:5,4-b′]dipyridin-5(5aH)-ylidene)benzene-1,4-diamine (CBD) was covalently grafted into these hexagonal tunnels, serving as light stimuli acceptor with loading content of 1.1μM/g. This composite was fully characterized and confirmed by SEM, TEM, XRD patterns, N2 adsorption/desorption, thermogravimetric analysis, IR, UV–vis absorption and emission spectra. Experimental data suggested that this composite had a core as wide as 150nm and could be magnetically guided to specific sites. Its hexagonal tunnels were as long as 180nm. Upon light stimuli of “on” and “off” states, controllable release was observed with short release time of ~900s (90% capacity).

Eccentric magnetic microcapsules for orientation-specific and dual stimuli-responsive drug release.

In this paper, we fabricated uniform polydimethylsiloxane (PDMS) magnetic microcapsules with eccentric internal structures and employed them as a novel delivery system for orientation-specific and dual stimuli-responsive controlled drug release. These eccentric microcapsules contained Fe3O4 nanoparticles in their inner cores. Because of the paramagnetic Fe3O4 nanoparticles, the eccentric microcapsules could be accurately moved by a magnetic field, leading to the precise control of the microcapsule locations. Also, due to the eccentric structures of the magnetic microcapsules, the capsules exhibited a non-uniform magnetic property; the capsules could be aligned by magnetic fields with their thin walls facing the magnet, resulting in a precise orientation-specific control of the microcapsules. More interestingly, the eccentric magnetic microcapsules demonstrated a dual stimuli-responsive controlled release of inclusions involving a sustained release under ultrasound and an intense release under laser stimulation. Furthermore, we studied the efficacy of doxorubicin (DOX) release from the microcapsules regulated by laser stimulation by performing in vitro cell tests with and without an applied magnetic field. The cell tests showed that the orientation-specific control of the microcapsules under a magnetic field (when the thin walls of the eccentric microcapsules were oriented towards the cell) improved the efficacy of the drug released from the microcapsules. The results suggested that our eccentric magnetic microcapsules hold all the properties needed for a site-specific, orientation-specific and dual stimuli-responsive delivery system, demonstrating a great potential application for multifunctional controlled drug release.

A novel collagen-nanohydroxyapatite microRNA-activated scaffold for tissue engineering applications capable of efficient delivery of both miR-mimics and antagomiRs to human mesenchymal stem cells

Manipulation of gene expression through the use of microRNAs (miRNAs) offers tremendous potential for the field of tissue engineering. However, the lack of sufficient site-specific and bioactive delivery systems has severely hampered the clinical translation of miRNA-based therapies. In this study, we developed a novel non-viral bioactive delivery platform for miRNA mimics and antagomiRs to allow for a vast range of therapeutic applications. By combining nanohydroxyapatite (nHA) particles with reporter miRNAs (nanomiRs) and collagen-nanohydroxyapatite scaffolds, this work introduces the first non-viral, non-lipid platform to date, capable of efficient delivery of mature miRNA molecules to human mesenchymal stem cells (hMSCs), a particularly difficult cell type to transfect effectively, with minimal treatment-associated cytotoxicity. Firstly, miRNAs were successfully delivered to hMSCs in monolayer, with internalisation efficiencies of 17.4 and 39.6% for nanomiR-mimics and nanoantagomiRs respectively, and both nanomiR-mimics and nanoantagomiRs yielded sustained interfering activity of greater than 90% in monolayer over 7days. When applied to 3D scaffolds, significant RNA interference of 20% for nanomiR-mimics and 88.4% for nanoantagomiRs was achieved with no cytotoxicity issues over a 7day period. In summary, in-house synthesised non-viral nHA particles efficiently delivered reporter miRNAs both in monolayer and on scaffolds demonstrating the immense potential of this innovative miRNA-activated scaffold system for tissue engineering applications.

Editorial (Thematic Issue: Oral Delivery of Biotechnology based Drugs: Dream or Reality?)

Biotechnology has provided a wide array of therapeutic agents such as peptide, protein, vaccine and gene products that are currently mainly administered by means of injections. Therapeutic agents produced by biotechnological processes such as recombinant DNA technology, fermentation, tissue and cell culture technology as well as genetic engineering are usually large, hydrophilic molecules facing delivery challenges, for example, these drugs are susceptible to degradation and are generally poorly membrane permeable. Since successful delivery of any drug is a pre-requisite to achieve the therapeutic goal, novel strategies have emerged in the late 20th century to overcome challenges associated with the oral route of drug administration. These strategies include, but are not restricted to micro- and nanotechnology including self-emulsifying lipid based formulations, dendrimers and devices, permeability enhancing technology, targeting of active transporters and membrane receptors, use of cell penetrating peptides, chemical modifications of peptides such as inclusion complex formation and peptide conjugates, site-specific delivery systems, muco-adhesive systems and polymeric hydrogels. Despite the initial excitement regarding the potential of these technologies to provide effective oral delivery, few have advanced from the pre-clinical stage into clinical trials and very few, if any, resulted so far in registered medicinal products. Moreover, most literature provides information on effectiveness and mechanisms based on in vitro investigations without revealing the viability of these technologies in clinical practice. Although this topic of oral peptide delivery has gone through different phases in terms of attracting attention from the scientific community, it remains a timely research subject. The therapeutic benefits to patients and potential economic benefits to the producer serve as the driving forces behind finding an effective oral delivery system for biotechnology derived drugs. This special issue aims at assessing some of the latest developments in the field of oral delivery of biotechnological therapeutic agents. The reader will not only gain an understanding of the challenges associated with oral delivery of protein and peptide based drugs, but certain strategies that emerged to overcome these drawbacks are also discussed. From the discussions it is clear that scientific research has contributed to a deeper understanding of older drug delivery strategies, while new discoveries keep the vision of producing an effective oral peptide drug delivery system alive.

Site specific solubility improvement using solid dispersions of HPMC-AS/HPC SSL – Mixtures

Many upcoming drug candidates are pH-dependent poorly soluble weak bases in the pH range of the gastrointestinal tract. This often leads to a high in vivo variability and bioavailability issues. Aiming to overcome these limitations, the design of solid dispersions for site specific dissolution improvement or maintenance of a potent supersaturation over the entire gastro-intestinal pH-range, is proposed to assure a reliable drug therapy. Solid dispersions containing different ratios of Dipyridamole (DPD) or Griseofulvin (GRI) and the enteric polymer hydroxypropylmethylcellulose-acetate succinate (HPMC-AS) and the water soluble low-viscosity hydroxypropylcellulose (HPC-SSL) were prepared by hot melt extrusion (HME). The solid dispersions were evaluated for their solid state, dissolution characteristics applying a three pH-step dissolution method following an acidic to neutral pH transition and stability. The use of HPMC-AS in binary mixtures with DPD and GRI facilitated increased solubility and supersaturation at pH-controlled release of the preserved amorphous state of the dispersed drug, which even inverted the pH-dependent solubility profile of the weakly basic model drug (Dipyridamole). I.e. a potent site specific delivery system was created. With ternary solid dispersions of API, HPMC-AS and HPC-SSL, tailored release profiles with superior supersaturation over the applied pH-range could be obtained. At the same time, binary and ternary mixtures showed favorable stability properties at a temperature difference between glass transition temperature and the applied storage temperature of down to 16°C.

Pioglitazone hydrochloride: chemopreventive potential and development of site-specific drug delivery systems

The aim of this study was to investigate the potential of pioglitazone hydrochloride as a promising anticancer agent and then to design and evaluate the colon-targeted delivery system. The role of pioglitazone hydrochloride as a promising anticancer agent was evaluated by in vitro cell line studies and in vivo 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. In order to deliver the drug at site of action, i.e. colon, drug embedded in matrices containing a release retarding polymer (HPMC K4M) and a polysaccharide (locust bean gum) were prepared. These matrix systems were further enteric coated with Eudragit®S100 to minimize the premature drug release in the upper segments of the GIT. In vitro dissolution studies were performed in absence and presence of rat caecal contents on selected batches and samples were analyzed using a validated RP-HPLC method. Hence, the studies led to the conclusion that successful site-specific delivery systems of pioglitazone hydrochloride were developed to improve its therapeutic efficacy in the management of colorectal cancer.

Gene therapy for in-stent restenosis: Targets and delivery system

the advent of the drug-eluting stent, the incidence of in-stent restenosis remains unacceptably high. Gene therapeutic strategies, including catheter-based gene delivery and gene-eluting stents, offer novel treatment methods to promote re-endothelialization, and inhibit inflammation, neointimal hyperplasia and late stent thrombosis. The translation of gene therapy into clinical application must be safe and requires an effective, site-specific delivery system as well as the ability to provide sustained transgene expression. The progress of magnetic nanotechnology and genetic engineering of human stem cells can provide such elements. In the present review, the authors discuss the evolution of antirestenosis therapy, underlying mechanisms of restenosis and the applications of gene therapy to prevent in-stent restenosis. Current gene delivery methods, including gene vectors and delivery strategies, are critically reviewed.

Development and evaluation of nifidipine loaded tablet formulation for colon drug delivery

Pulsatile release profile is characterized by a lag time followed by rapid and complete drug release. Pulsatile drug delivery systems are classified into time-controlled and site-specific delivery systems. The lag time is taken as the time of less than 10% drug release. The objective of present study was to develop a pulsatile compression coated tablet. The system was developed into two steps i.e. firstly core tablet was prepared containing Nifidipine; secondly core tablet was coated with polymer blend of ethyl cellulose (water insoluble polymer) and Eudragit L 100 (Enteric polymer). From the study it was concluded that the formulation having a coating level of 50% w/w of core and weight ratio of ethyl cellulose to Eudragit L 100 (20%) showed lesser release profile as compared to other formulation i.e. 52.83% in 12hrs. As we increase the weight ratio of ethyl cellulose to Eudragit L 100 better entrapment of drug leading to controlled release of drug.

β-Cyclodextrin-Bearing Gold Glyconanoparticles for the Development of Site Specific Drug Delivery Systems

Three novel gold nanoparticles containing multiple long, flexible linkers decorated with lactose, β-cyclodextrin, and both simultaneously have been prepared. The interaction of such nanoparticles with β-d-galactose-recognizing lectins peanut agglutinin (PNA) and human galectin-3 (Gal-3) was demonstrated by UV-vis studies. Gal-3 is well-known to be overexpressed in several human tumors and can act as a biorecognizable target. This technique also allowed us to estimate their loading capability toward the anticancer drug methotrexate (MTX). Both results make these glyconanoparticles potential site-specific delivery systems for anticancer drugs.

On a site-specific delivery system based on core–shell structured magnetic particles: Preparation and characterization

In the present work, core–shell structured submicro particles with light-switch of azobenzene were developed as a site-specific delivery system. The core was composed of magnetic Fe3O4 submicro particles, providing the magnetism-guiding and targeting function, and the outer shell was composed of mesoporous silica structure, providing solid mesoporous channels, large surface area, tunable pore sizes and volumes for cargo molecules. The light switch of azobenzene was covalently grafted onto the backbone of the outer shell. The core–shell structured submicro particles were characterized and identified by SEM, TEM, XRD, IR spectra, N2 adsorption/desorption isotherms, UV–Vis absorption and emission spectra. Experiment data confirmed the successful preparation of core–shell structured submicro particles with light-switch of azobenzene. The magnetic core was as wide as ∼160nm and the outer shell was found to own mesopores to load cargo molecules. The controllable release character of these submicro particles was also investigated. With the help of light-switch of azobenzene, controllable release of cargo molecules was successfully realized.

In vivo PEG modification of vascular surfaces for targeted delivery

Thrombosis and restenosis remain problematic for many intravascular procedures. Previously, it has been demonstrated that modifying an injured vascular surface with a protein-reactive polymer could block undesirable platelet deposition. As an added benefit, it would be advantageous if one could target therapeutics to the injured site. This study investigates a site-specific delivery system to target microspheres to vascular surfaces modified with a reactive polyethylene glycol tagged with biotin. Rabbit femoral arteries were injured with a 2F embolectomy catheter. Modification of the vascular surface was achieved using a channeled balloon catheter or small-diameter tube. Microspheres were injected intravenously through catheterization of the ear vein. Polymer modification on the injured surface and delivery of microspheres was quantified using epifluorescence microscopy at 0, 24, 48, and 72 hours. Polymer modification of the vascular surface could be achieved using a channeled drug delivery catheter or small-diameter tube with similar results. Maximum polymer coverage occurred at 0 hours and decreased to 85% maximal at 24 hours, 72% at 48 hours, and 67% at 72 hours. The initial number of microspheres per mm(2) binding to modified, injured arteries was 304 versus 141 for the unmodified, damaged control (P < .01). At subsequent times, the number of adherent microspheres to modified, injured arteries decreased by 50%, 70%, and 84% at 24, 48, and 72 hours, respectively; while nonspecific binding to unmodified, injured arteries quickly decreased by 93%. Initial microsphere binding to modified, healthy arteries was 153 microspheres/mm(2) as opposed to 26 microspheres/mm(2) for the unmodified, healthy controls (P < .01). Chemical modification of injured vessels following intravascular procedures can be readily accomplished in vivo to create a substrate for targeted delivery systems. As a proof of concept, targeted microspheres preferentially adhered to polymer-modified surfaces as opposed to injured, unmodified, or healthy vascular surfaces.

Comparison of the Gastrointestinal Absorption and Bioavailability of Fenofibrate and Fenofibric Acid in Humans

This study compared the gastrointestinal (GI) absorption characteristics and absolute bioavailability of fenofibric acid and fenofibrate (which is converted to fenofibric acid in vivo) in healthy volunteers. Treatments were delivered to the proximal small bowel, distal small bowel, and colon using a site-specific delivery system (Enterion capsule) and to the stomach by oral administration of equimolar doses. Serial blood samples were collected for 120 hours postdose and assayed for plasma fenofibric acid concentrations. The absolute bioavailability of each treatment was determined relative to 50 mg of fenofibric acid administered intravenously. Plasma exposure to fenofibric acid following fenofibric acid administration was approximately 1.5 times higher than that following fenofibrate administration for delivery to the proximal and distal small bowel and following oral administration, and it was approximately 5 times higher following colon delivery. The absolute bioavailability in the stomach, proximal small bowel, distal small bowel, and colon was approximately 81%, 88%, 84%, and 78%, respectively, for fenofibric acid and 69%, 73%, 66%, and 22%, respectively, for fenofibrate (P < .0001 and P = .033 for fenofibric acid vs fenofibrate in the colon and distal small bowel, respectively). In conclusion, fenofibric acid is well absorbed throughout the GI tract and has greater bioavailability than fenofibrate in all GI regions.

Artesunate-clindamycin multi-kinetics and site-specific oral delivery system for antimalaric combination products

The aim of this work was to study a multi-kinetics and site-specific oral antimalaria drug delivery system (MKS_DDS), containing artesunate and clindamycin, based on the Dome Matrix® module assembly technology. The MKS_DDS assembled system comprises of four modules, i.e., two controlled release (CR) modules for delivery of 160 mg of clindamycin phosphate, one immediate release module containing 50 mg of artesunate and one immediate release module containing 80 mg of clindamycin phosphate. These modules have been assembled in stacked and void configurations. The void configuration is able to float and showed gastro-retentive behavior. The MKS_DDS was investigated for its mechanical characteristics, system behavior during release, drug release rate and mechanism. A bioavailability study (dogs) showed that the clindamycin plasma curve of the MKS_DDS system exhibited a quasi constant release rate, up to 8 h. The MKS_DDS system containing clindamycin and artesunate allows the use of one tablet containing one immediate release dose of artesunate and of clindamycin and a portion of clindamycin released over a prolonged time, by exploiting the gastro-retentive properties of a floating system.

Stavudine-loaded mannosylated liposomes: in-vitro anti-HIV-I activity, tissue distribution and pharmacokinetics

Cells of the mononuclear phagocyte system (MPS) are important hosts for human immunodeficiency virus (HIV). Lectin receptors, which act as molecular targets for sugar molecules, are found on the surface of these cells of the MPS. Stavudine-loaded mannosylated liposomal formulations were developed for targeting to HIV-infected cells. The mannose-binding protein concanavalin A was employed as model system for the determination of in-vitro ligand-binding capacity. Antiretroviral activity was determined using MT-2 cell line. Haematological changes, tissue distribution and pharmacokinetic studies of free, liposomal and mannosylated liposomal drug were performed following a bolus intravenous injection in Sprague-Dawley rats. The entrapment efficiency of mannosylated liposomes was found to be 47.2 +/- 1.57%. Protein-carbohydrate interaction has been utilized for the effective delivery of mannosylated formulations. Cellular drug uptake was maximal when mannosylated liposomes were used. MT2 cells treated continuously with uncoated liposomal formulation had p24 levels 8-12 times lower than the level of free drug solution. Further, the mannosylated liposomes have shown p24 levels that were 14-20 and 1.4-2.3 times lower than the level of free drug and uncoated liposomal formulation treatment, respectively. Similar results were observed when infected MT2 cells were treated overnight. Stavudine, either given plain or incorporated in liposomes, led to development of anaemia and leucocytopenia while mannosylated liposomes overcame these drawbacks. These systems maintained a significant level of stavudine in the liver, spleen and lungs up to 12 h and had greater systemic clearance as compared with free drug or the uncoated liposomal formulation. Mannosylated liposomes have shown potential for the site-specific and ligand-directed delivery systems with desired therapeutics and better pharmacological activity.

Ion Exchange Resins Transforming Drug Delivery Systems

Ion-exchange resins are light, porous, three-dimensional high molecular weight cross -linked matrix of hydrocarbon chains carrying positively or negatively charged sites that can attract an ion of opposite charge from the surrounding medium. There is stoichiometric exchange of mobile ions between the solid and the solution called as Ion-exchange which does not lead to any radical change in the properties and structure of the solid. Depending upon the type of Ion-exchanged it can be either Cation-exchange or Anion-exchange. They are prepared in the form of granules, beads or sheets. As drug delivery systems they have received considerable attention after the 1950s due to their inertness, freedom from side effects, high drug loading capacity, ease of sterilization and the fact that their structure can be easily altered to achieve the desired drug release characteristics. Their use is revolutionizing all traditional delivery systems namely- oral, nasal, ophthalmic and parenteral. Ion- exchange resins have been used for the development of novel drug delivery systems (NDDSs), to modify the characteristics of the dosage form and various other biomedical applications. The present article deals with the varied applications of ion-exchange resins for taste making, as resinates (simple and microencapsulated or coated), Pennkinetic systems, in selective recovery of pharmaceuticals, in pH and ionic strength responsive systems, in gastro-retentive systems, in hollow fiber systems, as sigmoidal release systems, as site specific delivery systems and as inotophoretically assisted transdermal drug delivery systems. They also have an immense importance when used as disintegrants / superdisintegrants in formulation of orodispersible tablets, powder processing aids and in the dissolution and stabilization of drugs.

PREPARATION AND EVALUATION OF CIPROFLOXACIN/CHITOSAN IMPLANTS AS A CONTROLLED BIODEGRADABLE DRUG DELIVERY SYSTEM

This work aimed to prepare and evaluate physically crosslinkedimplantable matrices based on chitosan as a site-specificdelivery of ciprofloxacin hydrochloride (CFX.HCl) for theprevention of post-surgical wound infection. Biodegradablematrices were prepared from chitosan and different polyanionpolymers by direct compression. The potential of formulationvariables on the in-vitro drug release from polymeric matrices hasbeen studied. A matrix system of CFX.HCl based on the polyanioncomplex of chitosan and pectin showed a sustainable drug releaseover three days. The swelling and in-vitro drug release experimentssuggested that complex formation between chitosan and pectin hasoccurred at ratio 1:2. The results also suggested that CFX.HClrelease from chitosan matrices was markedly influenced by thenature of polyanion polymers, mixing ratio and total weight ofmatrices, whereas the compression force did not significantly affectthe drug release. With increasing CFX.HCl loading, a decrease ofthe percent cumulative release was observed. Approximately 13%of loaded drug was released from matrix containing 25% w/w drugduring 72 hrs in phosphate buffer pH 7.4. Fitting the in-vitro drugrelease data to Korsmeyer equation indicated that combined effectof diffusion and polymer chain relaxation could be the mechanismsof drug release. Microbiological simulated test revealed theefficient microbial inhibitory effect of chitosan: pectin (1:2) matrixwith 25% drug load over extended period of time.In conclusion: Cross-linked chitosan implantable device forseptic wounds or post surgical treatment with antimicrobialcapability and wound healing properties was developed to serve asa site-specific delivery system for antibiotics.

Recent Advances in Oral Pulsatile Drug Delivery

Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

Functionalized nanocarrier(s) to image and target fungi infected immune cells

The present study was aimed at the preparation, characterization, and evaluation of the performance of amphotericin B (AmB)-loaded aerosolized liposomes and emulsomes (core composed of solid lipid surrounded by phospholipid bilayers) for their selective presentation to lungs (alveolar macrophages), as this is the densest site of aspergillosis infection. Liposomes and emulsomes were modified by coating them with alveolar macrophage-specific ligands (O-palmitoyl mannan, OPM) and also with monoclonal antibody EBA-2. The prepared formulations were characterized in vitro for vesicle size, zeta potential and percent drug entrapment. We evaluated the therapeutic efficacy of the novel site-specific targetable lipid-based delivery systems in experimental pulmonary aspergillosis. Immunosuppressed rats with pulmonary aspergillosis were given 1 mg/kg of aerosolized liposomal and emulsomes formulations of AmB once by using an ultrasonic jet nebulizer on the third day after infection. The concentrations of AmB in lung were higher in surface modified liposomes and emulsomes than those of plain counterparts. Changes in lung histopathology were also assessed. Further, scintigraphy was also carried out using 99mTc labeled liposomes. From those results it was concluded that radiolabeled liposomes could be used for in vivo imaging of the infection site, and that site directed system(s) based on OPM/mAb coating exhibited great potential in targeted antifungal chemotherapy.