Colonic drug delivery: an updated review

Specific targeting of drug to the colon is recognized to have several therapeutic advantages. Drugs that are destroyed by the acidic environment of the stomach or metabolized by pancreatic enzymes are only slightly affected in the colon. Sustained colonic delivery of drugs can be useful in the treatment of nocturnal asthma, angina, and arthritis. Treatment of colonic diseases such as ulcerative colitis, Crohn's disease, and colorectal cancer is more effective with direct delivery of drugs to the colon. This article is aimed at providing insight into the design considerations and evaluation of colonic drug delivery systems. The anatomy and physiology of the lower gastrointestinal tract is discussed; then the biopharmaceutical aspects are considered in relation to drug absorption in the colon. Various approaches to colon-specific drug delivery are discussed.     

Pectin/Ethylcellulose as film coatings for colon-specific drug delivery: preparation and in vitro evaluation using 5-fluorouracil pellets

The aim of the present study is to develop colon-targeted drug delivery systems for 5-fluorouracil using pectin combined with ethylcellulose as a film coat with fluidized bed coater. Pellets (0.8-1.0 mm in diameter) containing 40% 5-fluorouracil and 60% microcrystalline cellulose were prepared by extrusion and spheronization. Film-coated pellets of 5-fluorouracil containing various proportions (1:0, 0:1, 1:1, 1:2, w/w) of pectin and ethylcellulose (Surelease) were prepared and subjected to in vitro drug release. The amount of 5-fluorouracil released from pellets at different time intervals was estimated by high-performance liquid chromatography. Drug release was assessed using flow testing in the presence and absence of rat caecal contents. The film thickness is expressed as the theoretical percentage of the weight gained (TWG-%) used relative to the weight of the coated pellets. Coated pellets with pectin alone and TWG-20% released 100% of the 5-fluorouracil in the simulated gastric and small intestinal conditions and failed to control the drug release in the first 5 h of the dissolution study in the simulated gastric and small intestinal conditions; while coated pellets with ethylcellulose alone and TWG-20% released 11.7 +/- 0.9% of the 5-fluorourail at the end of 24 h. When the ratio of pectin to Surelease was 1:1 (w/w) and film coat TWG-20%, the release was rapid and was accompanied by splitting of the coat. When the ratio of pectin to Surelease was 1:2 (w/w) and film coat TWG-13% and TWG-20%, the formulations released 9.8 +/- 0.7% and 4.1 +/- 0.4%, respectively, of 5-fluorouracil in the first 5 h of the dissolution study in the simulated gastric and small intestinal conditions. When the dissolution study was continued in simulated colonic fluids (4% w/v rat caecal content medium) for another 19 h, the film coat with the formulations of TWG-13% and TWG-20% released 96 +/- 1.3% and 85.0 +/- 0.3%, respectively, of 5-fluorourail in simulated colonic fluids at the end of 24 h of the dissolution study, whereas in the control study the formulations released 51.4 +/- 1.0% and 34 +/- 0.5%, respectively, of 5-fluorouracil in absence of rat caecal contents at the end of 24 h. The results of the study show that the formulation of TWG-20% (pectin to Surelease 1:2, w/w) is most likely to provide targeting of 5-fluorouracil for local action in the colon, as it released only 4.1 +/- 0.4% of the drug in the simulated gastric and small intestinal conditions, and it released 85.0 +/- 0.3% of 5-fluorourail in simulated colonic fluids at the end of 24 h. The 5-fluorouracil-coated pellets showed no change in physical appearance, drug content, or dissolution pattern after storage at 40 degrees C/75% relative humidity for 6 months. Differential scanning calorimetric study indicated no possibility of interaction between 5-fluorouracil and pectin or other excipients used in the coated pellets.     

Binders for colon specific drug delivery: an in vitro evaluation

In order to screen out an optimum complex for reducing the nephrotoxicity of cisplatin (CDDP), we investigated and compared CDDP–chondroitin sulfate complexes to CDDP in terms of in vivo pharmacokinetics and in vitro cytotoxicity. The polymeric carriers used in the study were chondroitin sulfate A (CSA, 4-sulfate) with mean molecular weights of 10 kDa (CSA-1) and 23 kDa (CSA-2), and chondroitin sulfate C (CSC, 6-sulfate) with mean molecular weights of 8 kDa (CSC-1) and 25 kDa (CSC-2). The resultant complexes (CDDP–CSA-1, CDDP–CSA-2, CDDP–CSC-1 and CDDP–CSC-2) were administered intravenously to rats. The obtained plasma concentration–time curves during the 3 h period studied for all complexes are biphasic. The plasma dispositions of complexes were dependent on the molecular sizes with urinary excretion as main elimination pathway. CDDP–CSA-1 and CDDP–CSC-1 were unable to effectively increase the plasma retention of platinum due to rapid renal excretion. Furthermore, CDDP–CSA-1 disappeared from plasma more quickly than CDDP–CSC-1. CDDP–CSA-2 and CDDP–CSC-2, with similar urinary excretion as CDDP, gave rise to approximately five and four-fold increase in AUC_{0–3 h} values, respectively, than that was achieved with native CDDP treatment. Biodistribution was compared between CDDP–CSA-2 and CDDP–CSC-2. Both complexes effectively suppressed the extensive distribution of CDDP into most tissues, especially kidney. However, CDDP–CSC-2 showed less reduction effect than CDDP–CSA-2. In addition, a significantly higher accumulation in tumor tissue was found with the administration of CDDP–CSA-2 than CDDP. Moreover, CSA complexes displayed an IC₅₀ of 6 μM Pt-equivalents against SW4800 human colon cancer cells, similar to that of CDDP, whereas CSC complexes were less active than CDDP. These studies indicate that the complex prepared with CSA, which is greater than 20 kDa of molecular size, is superior to that of CSC, exhibiting improved pharmacokinetics and similar pharmacological activity to the native drug.     

In vitro drug release studies on guar gum-based colon targeted oral drug delivery systems of 5-fluorouracil.

Intravenous administration of 5-fluorouracil for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The broad objective of the present study was to develop novel tablet formulations for site-specific delivery of 5-fluorouracil to the colon without the drug being released in the stomach or small intestine using guar gum as a carrier. Fast-disintegrating 5-fluorouracil core tablets were compression coated with 60% (FHV-60), 70% (FHV-70) and 80% (FHV-80) of guar gum, and were subjected to in vitro drug release studies. The amount of 5-fluorouracil released from the compression-coated tablets in the dissolution medium at different time intervals was estimated by a HPLC method. Guar gum compression-coated tablets released only 2.5-4% of the 5-fluorouracil in simulated GI fluids. When the dissolution study was continued in simulated colonic fluids (4% w/v rat caecal content medium) the compression-coated FHV-60, FHV-70 and FHV-80 tablets released another 70, 55 and 41% of the 5-fluorouracil respectively. The results of the study show that compression-coated tablets containing 80% (FHV-80) of guar gum are most likely to provide targeting of 5-fluorouracil for local action in the colon, since they released only 2.38% of the drug in the physiological environment of the stomach and small intestine. The FHV-80 formulation showed no change either in physical appearance, drug content or dissolution pattern after storage at 40 degrees C/RH 75% for 6 months. The differential scanning calorimetric study showed that 5-fluorouracil did not interact with the formulation excipients used in the study.     

Formulation and evaluation of cholesterol-rich nanoemulsion (LDE) for drug delivery potential of cholesteryl-maleoyl-5-fluorouracil

Abstract

It has been reported that cholesterol-rich nanoemulsions (LDE) can bind to low density lipoprotein (LDL) receptors which can concentrate anticancer drugs in the tissues via LDL receptor overexpression and reduced the adverse effects of the treatment. Therefore, in this study, LDE nanoemulsions of cholesteryl-maleoyl-5-fluorouracil (5-FU conjugate) were developed and evaluated in vitro. LDE nanoemulsions were prepared by high-energy emulsification technique. Developed formulations were characterized in terms of droplet size, polydispersity index, zeta potential, viscosity and refractive index. Optimized formulation (L5) was also evaluated for surface morphology using transmission electron microscopy (TEM). Developed formulations were subjected to in vitro drug release studies through dialysis membrane. The droplet size (50?nm), polydispersity index (0.109) and viscosity (32.16 cp) were found to be lowest for optimized formulation L5. The results of zeta potential indicated the stable formation of developed LDE nanoemulsions. TEM images of optimized formulation indicated non-spherical shape of droplets. About 97% of conjugate was found to be released from L5 after 24?h of study. Overall, these results indicated that developed LDE nanoemulsions could be successfully used for oral delivery of 5-FU conjugate.     

Colonic delivery of dexamethasone: a pharmacoscintigraphic evaluation

Background: Colonic delivery of corticosteroids may reduce the side-effects commonly associated with their use. Therefore, we tested the ability of the naturally occurring polysaccharide guar gum to deliver a corticosteroid, dexamethasone, to the colon using pharmacoscintigraphy. Guar gum is metabolized in the colon by resident bacterial enzymes to trigger drug release. Materials: Each subject (eight per group, parallel study design) was administered one of four dexamethasone (9 mg) tablet formulations, radiolabelled with ¹⁵³Sm using neutron activation, under fasted conditions. One formulation was designed to release drug rapidly following ingestion while the other three formulations were designed to delay release of dexamethasone to varying degrees. Progression of the formulations down the gastrointestinal tract was followed by gamma scintigraphy. Serum concentrations were measured over time to relate disintegration profiles of the tablets with pharmacokinetic observations. Results: The immediate release formulation disintegrated in the stomach, on average, within 20  min of dosing. One of the three delayed release preparations (CD₁) began to disintegrate in the small intestine 1.7±1.0 h after dosing. The second and third delayed release preparations (CD₂ and CD₃) did not begin to disintegrate until 5.8±2.3 and 3.6±1.6 h after dosing, respectively. All three colonic delivery preparations completely disintegrated in the colon ranging from 7.8±2.7 h (CD₁) to 12.4±3.2 h (CD₂) following oral administration. Pharmacoscintigraphic data indicated that 72–82% of the dexamethasone was delivered into the colon although not all the dexamethasone delivered into the colon was absorbed. Conclusions: Simple guar gum formulations are capable of delivering the corticosteroid dexamethasone to the colon of normal subjects. Locally delivered corticosteroids may be useful in the treatment of ulcerative colitis and Crohn's disease. Pharmacoscintigraphic evaluation is a useful method to discriminate between the in vivo behaviour of colonic delivery systems.     

Pectin/chitosan mixtures as coatings for colon-specific drug delivery: an in vitro evaluation

The ability of a multiple-unit dosage form to reach the colon intact has been investigated, in vitro, using conditions chosen to simulate the pH and times likely to be encountered during transit to the colon. Small tablets were coated with either pectin USP or pectin in a 1:10 mixture with chitosan. Indomethacin and paracetamol were used as model drugs to represent poorly soluble and soluble compounds. Pectin alone was able to protect the cores from premature release, but only when a substantially thick coat was present. Pectin/chitosan mixtures achieved better protection at a lower coat weight. The use of pectinolytic enzymes to simulate breakdown in the colon showed that the pectin/chitosan mixture was susceptible to enzymic breakdown and allowed drug release to occur. The importance of pre-exposure of the tablets to conditions in the upper gastro-intestinal tract prior to exposure to the enzyme was noted.     

Nanoemulsion gel-based topical delivery of an antifungal drug: in vitro activity and in vivo evaluation

Abstract

Objective: In this study, attempt has been focused to prepare a nanoemulsion (NE) gel for topical delivery of amphotericin B (AmB) for enhanced as well as sustained skin permeation, in vitro antifungal activity and in vivo toxicity assessment.

Materials and methods: A series of NE were prepared using sefsol-218 oil, Tween 80 and Transcutol-P by slow spontaneous titration method. Carbopol gel (0.5%?w/w) was prepared containing 0.1%?w/w AmB. Furthermore, NE gel (AmB-NE gel) was characterized for size, charge, pH, rheological behavior, drug release profile, skin permeability, hemolytic studies and ex vivo rat skin interaction with rat skin using differential scanning calorimeter. The drug permeability and skin irritation ability were examined with confocal laser scanning microscopy and Draize test, respectively. The in vitro antifungal activity was investigated against three fungal strains using the well agar diffusion method. Histopathological assessment was performed in rats to investigate their toxicological potential.

Results and discussion: The AmB-NE gel (18.09?±?0.6?µg/cm²/h) and NE (15.74?±?0.4?µg/cm²/h) demonstrated the highest skin percutaneous permeation flux rate as compared to drug solution (4.59?±?0.01?µg/cm²/h) suggesting better alternative to painful and nephrotoxic intravenous administration. Hemolytic and histopathological results revealed safe delivery of the drug. Based on combined results, NE and AmB-NE gel could be considered as an efficient, stable and safe carrier for enhanced and sustained topical delivery for AmB in local skin fungal infection.

Conclusion: Topical delivery of AmB is suitable delivery system in NE gel carrier for skin fungal infection.     

Niosomal delivery of 5-fluorouracil

Non-ionic surfactant vesicles (niosomes) have shown promise as cheap, chemically stable alternatives to liposomes. Niosomes of spans (Sorbitan monoesters) have shown promise of commercial exploitation. Hence, niosomes were prepared of 5-fluorouracil (FU) using different spans. Niomsomes were prepared bythehand shakingmethod (HSM), reversephaseevaporation(REV) and ether injection method (EIM) using a series of Spans, i.e. Span 20, 40, 60 and 80. HSM giving least permeable vesicles were used to study the effect of variables like type of Span, composition of lipid and total lipid concentration on entrapment efficiency (EE) and release rate. Span 40 and 60 released 40.9 and 37.1%drug in 6h while Span 20 and 80 displayed 52.2 and 57.1%release, respectively in the same time. Niosomes of Span 40 showed amean vesicle size of 8.1mum, EE of 15:3 1:3%and released 78.6% drug in 6h; inclusion of cholesterol reduced the vesicle size to4.8mum, EE to12:3 0:9%and the release to 50.5%(in 6h), while incorporation of dicetyphosphate further reduced the vesicle size to3.87mum, EE to10:9 1:1%and reduced release to40.9%(in 6h). Increase in the amount of lipid used translated intoan almost linear increase in EE. Biodistribution of drug in rats was modified on encapsulation. The concentration of niosomal drug in liver, lung and kidney was increased while it decreased in intestine compared to free drug solution following intravenous administration. The niosomal formulation displayed higher and sustained plasma drug level profile compared to free drug solution. Pharmacokinetic calculations revealed an increase in half-life, area under the curve and decrease in volume of distribution of the drug on encapsulation. Thus, the study suggests that niosomes can act as promising carriers for 5-Fluorouracil.     

Niosomal delivery of 5-fluorouracil

Non-ionic surfactant vesicles (niosomes) have shown promise as cheap, chemically stable alternatives to liposomes. Niosomes of spans (Sorbitan monoesters) have shown promise of commercial exploitation. Hence, niosomes were prepared of 5-fluorouracil (FU) using different spans. Niomsomes were prepared by the hand shaking method (HSM), reverse phase evaporation (REV) and ether injection method (EIM) using a series of Spans, i.e. Span 20, 40, 60 and 80. HSM giving least permeable vesicles were used to study the effect of variables like type of Span, composition of lipid and total lipid concentration on entrapment efficiency (EE) and release rate. Span 40 and 60 released 40.9 and 37.1% drug in 6 h while Span 20 and 80 displayed 52.2 and 57.1% release, respectively in the same time. Niosomes of Span 40 showed a mean vesicle size of 8.1 microns, EE of 15.3 +/- 1.3% and released 78.6% drug in 6 h; inclusion of cholesterol reduced the vesicle size to 4.8 microns, EE to 12.3 +/- 0.9% and the release to 50.5% (in 6 h), while incorporation of dicetyphosphate further reduced the vesicle size to 3.87 microns, EE to 10.9 +/- 1.1% and reduced release to 40.9% (in 6 h). Increase in the amount of lipid used translated into an almost linear increase in EE. Biodistribution of drug in rats was modified on encapsulation. The concentration of niosomal drug in liver, lung and kidney was increased while it decreased in intestine compared to free drug solution following intravenous administration. The niosomal formulation displayed higher and sustained plasma drug level profile compared to free drug solution. Pharmacokinetic calculations revealed an increase in half-life, area under the curve and decrease in volume of distribution of the drug on encapsulation. Thus, the study suggests that niosomes can act as promising carriers for 5-Fluorouracil.     

Imprinted hydrophilic nanospheres as drug delivery systems for 5-fluorouracil sustained release

Molecularly imprinted hydrogel nanospheres as devices for the controlled/sustained release of 5-fluororacil in biological fluids were synthesized employing one-pot precipitation technique as the polymerization method. Methacrylic acid as a functional monomer and ethylene glycole dimethacrylate as a cross-linker were used in polymeric feed. Morphological and hydrophilic properties were determined by scanning electron microscopy and water content measurement, and recognition and selectivity properties of spherical molecularly imprinted polymers were compared with the spherical non-imprinted polymers, both in organic (acetonitrile) and water media. Finally, in vitro release studies were performed in plasma simulating fluids.     

Polymeric microspheres for drug delivery to the oral cavity: an in vitro evaluation of mucoadhesive potential

Polymeric microparticles were fabricated from Carbopol, polycarbophil, chitosan, or Gantrez using a "water-in-oil emulsification" solvent evaporation method. Mean particle sizes, as determined by laser diffraction, were in the range 23-38 microm. Electron microscopy revealed that all microparticles were spherical and of smooth surface morphology. In pH 7.0 phosphate buffered saline, the microspheres exhibited significantly increased swelling ratios and longer half-times of swelling than the corresponding powdered polymers. The relative merits of the potential usefulness of these microspheres as formulation tools for the enhanced retention of a therapeutic entity within the oral mucosa were evaluated by in vitro mucoadhesion tests. Tensile tests showed that all microspheres under consideration were capable of adhering to porcine esophageal mucosa, with particles prepared from the poly(acrylic acid)s exhibiting greater mucoadhesive strength than those constructed from chitosan or Gantrez. However, in elution experiments involving a challenge with artificial saliva, particles of chitosan or Gantrez were retained onto mucosal tissue for longer time periods than those assembled from the poly(acrylic acid)s.     

Gastroretentive drug delivery system of metoclopramide hydrochloride: formulation and in vitro evaluation

The present investigation concerns the development of floating matrix tablets of metoclopramide hydrochloride (MHCl) for improving its bioavailability by prolonging gastric residence time. Floating matrix tablets (FMT) of MHCl were prepared using the polymers guar gum (GG), karaya gum (KG), HPMC E15 (HE) alone and in combination with HPMC K15M (HK) and gas generating agents such as calcium carbonate and citric acid. The fabricated tablets were evaluated for their physical characteristics such as hardness, drug content, buoyancy, swelling properties and in vitro release studies in 0.1N HCl. The tablets without gas generating agents and HK did not float at all whereas tablets with gas generating agents and without HK floated for 2.33-5.48 h then eroded completely and exhibited faster drug release. Tablets with gas generating agents and HK floated for 24 h without complete erosion and showed slower drug release. This indicates that gas generating agents contributes towards the initial floating of tablets and faster drug release and HK for maintaining the integrity of the FMT and sustaining the drug release. The increase in the concentration of HK in FMT from 10 mg to 40 mg resulted in decrease in release rate of drug. The possibility of drug polymer interaction was determined by differential scanning calorimetry (DSC) and fourier transform infrared (FTIR) spectrometer, and confirmed no interaction between drug and polymers. The release pattern of prepared tablets followed Higuchi kinetics which confirms release mechanism by diffusion.     

负载连翘苷的外泌体递药系统制备及体外评价

目的:制备负载连翘苷(phil)的外泌体(exos)递药系统(phil-exos),并考察其对人肺上皮腺癌细胞A549迁移能力的影响.方法:采用差速-超高速离心法结合超滤法获取小鼠肺泡巨噬细胞(MHS)来源的外泌体,超声法制备phil-exos并测定其粒径及电位,采用透射电子显微镜观察其形态,蛋白质免疫印迹法鉴定标志蛋...     

Design and in vitro evaluation of floating drug delivery system for an antipsychotic agent: a technical report

Floating drug delivery systems are used to target drug release in the stomach or to the upper parts of the intestine. The oral delivery of the anti-psychotic agent carbamazepine was facilitated by preparing a non-disintegrating floating dosage form which can increase its absorption in the stomach by increasing the drug's gastric residence time. The polymers used were HPMC (low and high viscosity), guar gum, and carbopol, along with sodium bicarbonate as the gas-generating agent. The prepared tablets were evaluated for their physicochemical properties and drug release. In vitro release studies indicated that the carbamazepine release from the floating dosage forms was uniform and followed a zero-order release. It was observed that the devices containing higher proportions of HPMC (high viscosity) showed slower release than those containing lower proportions while also maintaining the integrity of the device (> or = 24 h). The incorporation of guar gum helps to maintain the device's integrity, and due to its viscolysing property also affects the drug's release profile. Sodium bicarbonate which was used as the gas-generating agent causes the tablet to float for the required time (> or = 24 h).     

Coating polymers for colon specific drug delivery: a comparative in vitro evaluation

Colon is being extensively investigated as a drug delivery site. This study presents a comparison of the usual enteric coating polymers viz. Eudragit, cellulose acetate phathalate with shellac and ethyl cellulose, as carriers for colon specific drug delivery. Lactose based indomethacin tablets were prepared. These were coated with one of the coating polymers to a varying coat thickness. The coated formulations were evaluated for dissolution rates under simulated stomach and small intestine conditions. From the dissolution data obtained, it was found that the dissolution rate varied with the type and concentration of the polymer applied. Comparative dissolution data revealed that, of all the polymers and coat thicknesses used, a 3% (m/m) coat of shellac was most suitable for colonic drug delivery. It retarded drug release by 3-4 h (the usual small intestinal transit time) in simulated small intestinal fluid, whereafter a rapid drug release was observed.     

In vitro evaluation of dendrimer prodrugs for oral drug delivery

Dendrimer-based prodrugs were used to enhance the transepithelial permeability of naproxen, a low solubility model drug. The stability of the dendrimer-naproxen link was assessed. Naproxen was conjugated to G0 polyamidoamine (PAMAM) dendrimers either by an amide bond or an ester bond. The stability of G0 prodrugs was evaluated in 80% human plasma and 50% rat liver homogenate. The cytotoxicity of conjugates towards Caco-2 cells was determined and the transport of the conjugates across Caco-2 monolayers (37 degrees C) was reported. In addition, one lauroyl chain (L) was attached to the surface group of G0 PAMAM dendrimer of the diethylene glycol ester conjugate (G0-deg-NAP) to enhance permeability. The lactic ester conjugate, G0-lact-NAP, hydrolyzed slowly in 80% human plasma and in 50% rat liver homogenate (t(1/2)=180 min). G0-deg-NAP was hydrolyzed more rapidly in 80% human plasma (t(1/2)=51 min) and was rapidly cleaved in 50% liver homogenate (t(1/2)=4.7 min). The conjugates were non-toxic when exposed to Caco-2 cells for 3h. Permeability studies showed a significant enhancement in the transport of naproxen when conjugated to dendrimers; L-G0-deg-NAP yielding the highest permeability. Dendrimer-based prodrugs with appropriate linkers have potential as carriers for the oral delivery of low solubility drugs such as naproxen.     

In-vivo drug delivery of 5-fluorouracil using poly(2-hydroxyethyl methacrylate-co-acrylamide) hydrogels

Poly(2-hydroxyethyl methacrylate-co-acrylamide) hydrogels crosslinked with ethylen glycol dimethacrylate were used as devices for the in-vivo drug release of 5-fluorouracil (5-FU). Drug-loaded hydrogels were subcutaneously implanted in the back of Wistar rats. All hydrogel discs reached an equilibrium swelling degree, which was slightly larger than that determined in-vitro. After 30 days of implantation, the hydrogel discs were transparent, and without fracture or apparent degradation. In addition, a fibrous capsule was not detected around the hydrogels that had greater hydration degrees. Release of 5-FU from these hydrogels allows the drug to remain in the plasma from 1 to 5 days, in spite of its short plasma half-life (15 min). This was an improvement of up to 98-times compared with the intraperitoneal drug administration. Administration of 5-FU by implantation of 2-hydroxyethylmethacrylate-co-acrylamide copolymeric hydrogels seems to be a good candidate for 5-FU therapy, since the drug released results in a therapeutically suitable plasma concentration of 5-FU for an extended period of time, despite the short half-life of the drug.     

Dendrimer grafts for delivery of 5-fluorouracil

Polyamidoamine (PAMAM) dendrimers were prepared by linking methyl methacrylate and ethylenediamine successively on an amine core. Surface modification of PAMAM dendrimer was done by fatty acid grafting converting them to a unimolecular micellar system (Dendrimer grafts). IR, 1H NMR, 13C NMR studies confirmed the structure. The drug 5-fluorouracil (5-FU) was entrapped in dendrimer grafts. The effects of various solvents (ethanol, dichloromethane, tetrahydrofuran), pH and ionic strength on solubilization of 5-FU were determined. Phospholipid was further coated on the dendrimer grafts. The product was lyophilized and obtained as yellowish-white powder. Average particle size was ca. 375 nm as determined by Malvern's Mastersizer 4. Drug loading was ca. 53% by weight. Stability studies were conducted for 1 month at room temperature and 40 degrees C, where the systems were relatively stable. Release rate was sustained across cellulose tubing in PBS. In vivo studies were performed in albino rats and pharmacokinetic parameters and bioavailability were determined from the plasma profile of 5-FU. The phospholipid coated dendrimer graft formulation was found to be more effective orally than free drug. The lymphatic uptake was also increased indicating absorption of the developed formulation through the lymphatic route.