Evaluation of Plant-Based Silver Nanoparticles for Antioxidant Activity and Promising Wound-Healing Applications.

The current research focuses on the green synthesis of silver nanoparticles (AgNPs) using a polar extract of taro corms and the evaluation of its antioxidant properties and wound-healing applications. Taro corm extract (100 mL) was treated with a 5 mM AgNO3 solution (100 mL) at room temperature for the formation of AgNPs, and a color change was observed. The surface plasmon resonance (SPR) peaks in their UV-visible spectra appeared at a range of 438-445 nm. Fourier transform infrared, scanning electron microscopy, energy-dispersive X-ray, dynamic light scattering, and X-ray diffraction were used for the characterization of the taro corms extract-mediated AgNPs (TCE-AgNPs). The synthesized AgNPs were crystalline and spherical, with an average size of 244.9-272.2 nm with a polydispersity index of 0.530 and zeta potential of -18.8 mV, respectively. The antibacterial potential of TCE-AgNPs was tested, and the inhibition zones detected against Cronobacter sakazakii, Pseudomonas aeruginosa, Listeria monocytogenes, and Enterococcus faecalis were 28, 26, 18, and 13 mm, respectively. Furthermore, the antioxidant activity of TCE-AgNPs showed significant radical-scavenging activity compared to the standard used. Collagen content data collected from regenerated tissue and higher collagen content indicated rapid wound healing compared to others, which was seen in a group treated with TCE-AgNP film bandages.

Investigating the Impact of Carbon Nanotube Nanoparticle Exposure on Testicular Oxidative Stress and Histopathological Changes in Swiss albino Mice.

Carbon nanotubes (CNTs) possess remarkable properties that make them valuable for various industrial applications. However, concerns have arisen regarding their potential adverse health effects, particularly in occupational settings. The main aim of this research was to examine the effects of short-term exposure to multiwalled carbon nanotube nanoparticles (MWCNT-NPs) on testicular oxidative stress in Swiss albino mice, taking into account various factors such as dosage, duration of exposure, and particle size of MWCNT-NP. In this study, 20 mice were used and placed into six different groups randomly. Four of these groups comprised four repetitions each, while the two groups served as the vehicle control with two repetitions each. The experimental groups received MWCNT-NP treatment, whereas the control group remained untreated. The mice in the experimental groups were exposed to MWCNT-NP for either 7 days or 14 days. Through oral administration, the MWCNT-NP solution was introduced at two distinct dosages: 0.45 and 0.90 µg, whereas the control group was subjected to distilled water rather than the MWCNT-NP solution. The investigation evaluated primary oxidative balance indicators-glutathione (GSH) and glutathione disulfide (GSSG)-in response to MWCNT-NP exposure. Significantly, a noticeable reduction in GSH levels and a concurrent increase in GSSG concentrations were observed in comparison to the control group. To better understand and explore the assessment of the redox status, the Nernst equation was used to calculate the redox potential. Intriguingly, the calculated redox potential exhibited a negative value, signifying an imbalance in the oxidative state in the testes. These findings suggest that short-term exposure to MWCNT-NP can lead to the initiation of testicular oxidative stress and may disrupt the male reproductive system. This is evident from the alterations observed in the levels of GSH and GSSG, as well as the negative redox potential. The research offers significant insights into the reproductive effects of exposure to MWCNTs and emphasizes the necessity of assessing oxidative stress in nanomaterial toxicity studies.

Formulation and Characterization of Curcumin Niosomes: Antioxidant and Cytotoxicity Studies.

Curcumin's applications in the treatment of conditions including osteoarthritis, dementia, malignancies of the pancreas, and malignancies of the intestines have drawn increasing attention. It has several wonderful qualities, including being an anti-inflammatory agent, an anti-mutagenic agent, and an antioxidant, and has substantially reduced inherent cytotoxicity outcomes. Although curcumin possesses multiple known curative properties, due to its limited bioavailability, it is necessary to develop efficient strategies to overcome these hurdles. To establish an effective administration method, various niosomal formulations were optimized using the Box-Behnken design and assessed in the current investigation. To examine the curcumin niosomes, zeta sizer, zeta potential, entrapment efficiency, SEM, antioxidant potential, cytotoxicity, and release studies were performed. The optimized curcumin niosomes exhibited an average particle size of 169.4 nm, a low PDI of 0.189, and high entrapment efficiency of 85.4%. The release profile showed 79.39% curcumin after 24 h and had significantly higher antioxidant potential as compared with that of free curcumin. The cytotoxicity results of curcumin niosomes presented increased mortality in human ovarian cancer A2780.

A novel pH-responsive hydrogel system based on Prunus armeniaca gum and acrylic acid: Preparation and evaluation as a potential candidate for controlled drug delivery.

pH-responsive hydrogels have become effective and attractive materials for the controlled release of drugs at pre-determined destinations. In the present study, a novel hydrogel system based on Prunus armeniaca gum (PAG) and acrylic acid (AA) was prepared by a free radical mechanism using N, N-methylene bisacrylamide (MBA) as cross-linker and potassium persulfate (KPS) as initiator. A series of hydrogels varying PAG, AA, and MBA concentration was developed to determine the impact of these components. Formulated hydrogels were characterized for pH-responsive swelling, drug release, gel content, and porosity. Structural analysis was performed by FTIR, XRD, and SEM analysis. TGA study was applied to assess thermal stability. Oral acute toxicity and in vivo drug release were performed in rabbits. Hydrogels exhibited pH-dependent swelling and drug release. Swelling, drug loading and release, and porosity increased by increasing PAG and AA concentration while decreased by increasing MBA. The gel content of formulations was increased by increasing all three components. FTIR studies confirmed the development of copolymeric networks and the loading of drug. XRD studies revealed that hydrogels were amorphous, and the crystalline drug was changed into an amorphous form during loading. TGA results indicated that hydrogels were stable up to 600 °C. Acute oral toxicity results confirm that hydrogels were nontoxic up to a dose of 2 g/kg body weight in rabbits. The pharmacokinetic evaluation revealed that hydrogels prolonged the availability of the drug and the peak plasma concentration of the drug was obtained in 6 h as compared to the oral solution of the drug. Tramadol hydrochloride (THC) was used as a model drug. Hence, pH-responsive swelling and release, nontoxic nature and improved pharmacokinetics support that PAG-based hydrogels may be considered as potential controlled-release polymeric carriers.

Maximizing the extraction yield of plant gum exudate using response surface methodology and artificial neural networking and pharmacological characterization.

Prunus armeniaca gum is used as food additive and ethno medicinal purpose. Two empirical models response surface methodology and artificial neural network were used to search for optimized extraction parameters for gum extraction. A four-factor design was implemented for optimization of extraction process for maximum yield which was obtained under the optimized extraction parameter (temperature, pH, extraction time, and gum/water ratio). Micro and macro-elemental composition of gum was determined by using laser induced breakdown spectroscopy. Gum was evaluated for toxicological effect and pharmacological properties. The maximum predicted yield obtained by response surface methodology and artificial neural network was 30.44 and 30.70% which was very close to maximum experimental yield 30.23%. Laser induced breakdown spectroscopic spectra confirmed the presence Calcium, Potassium, Magnesium, Sodium, Lithium, Carbon, Hydrogen, Nitrogen and Oxygen. Acute oral toxicity study showed that gum is non-toxic up to 2000 mg/Kg body weight in rabbits, accompanied by high cytotoxic effects of gum against HepG2 and MCF-7cells by MTT assay. Overall, Aqueous solution of gum showed various pharmacological activities with significant value of antioxidant, antibacterial, anti-nociceptive, anti-cancer, anti-inflammatory and thrombolytic activities. Thus, optimization of parameters using mathematical models cans offer better prediction and estimations with enhanced pharmacological properties of extracted components.

Mimosa pudica mucilage nanoparticles of losartan potassium: Characterization and pharmacodynamics evaluation.

The current research was to develop nanoparticles based on Mimosa pudica mucilage (MPM) that could encapsulate losartan potassium (LP). Nanoparticles (NPs) produced through ionic-gelation method; the polymerization of the mucilage carried out using calcium chloride as cross-linking agent. The MPMLP-NPs demonstrated vastly enhanced pharmaceutical characteristics, presented discrete surface with spherical shape of 198.4-264.6 nm with PDI ranging 0.326-0.461 and entrapment efficiency was in the range of 80.65 ± 0.82-90.79 ± 0.96%. FTIR and DSC indicated the stability of drug during the formulation of nanoparticles. An acute oral toxicity investigation found no significant alterations in behavior and histopathology criteria. The MPMLP-NPs formulation revealed the better rates and sustained effect as assessed with the commercial product. Moreover, low dose of MPMLP-NPs showed similar anti-hypertensive effect as assessed with the marketed tablet.

In Vitro/In Vivo Evaluation of Clomipramine Orodispersible Tablets for the Treatment of Depression and Obsessive-Compulsive Disorder.

The first and only antidepressant drug on the market with solid proof of clinically significant serotonin and noradrenaline reuptake inhibition is clomipramine (CLP). However, significant first-pass metabolism reduces its absorption to less than 62%. It is heavily protein-bound and broadly dispersed across the body (9-25 L/kg volume of distribution). The purpose of this research was to formulate CLP orodispersible tablets that immediately enable the drug to enter the bloodstream and bypass systemic portal circulation to improve its bioavailability. A factorial design was employed using varied amounts of Plantago ovata mucilage (POM) as a natural superdisintegrant, as well as croscarmellose sodium and crospovidone as synthetic disintegrants. Their physiochemical compatibility was evaluated by FTIR, DSC/TGA, and PXRD analysis. The blend of all formulations was assessed for pre- and post-compaction parameters. The study found that tablets comprising Plantago ovata mucilage as a superdisintegrant showed a rapid in vitro disintegration time, i.e., around 8.39 s, and had an excellent dissolution profile. The anti-depressant efficacy was evaluated by an open-field test (OFT) and the forced swimming test (FST) was applied to create hopelessness and despair behavior as a model of depression in animals (Albino rats). The in vivo study revealed that the efficiency of the optimized formulation (F9) in the treatment of depression is more than the marketed available clomfranil tablet, and may be linked to its rapid disintegration and bypassing of systemic portal circulation.

Formulation, Statistical Optimization, and In Vivo Pharmacodynamics of Cydonia oblonga Mucilage/Alginate Mucoadhesive Microspheres for the Delivery of Metformin HCl.

In recent years, attention has shifted toward the utilization of natural polymers for encapsulation and sustained release of health-hazardous drugs. The purpose of this work is to define and assess the sustained delivery potential and mucoadhesive potential of a Cydonia oblonga mucilage (COM) and sodium alginate (Na-Alg)-constituting polymeric delivery carrier of antidiabetic drugs with a specific end goal to retain metformin HCl in the stomach while expanding the drug's bioavailability. Metformin HCl was encapsulated in mucoadhesive microspheres by an ionic gelation method. Polymers with different combinations were tried, and the resulting mucoadhesive COM/Na-Alg microspheres were assessed for particle size (mm) PS/Y1, drug encapsulation efficiency DEE (%)/Y2, and in vitro percentage cumulative drug release R12h/Y3 using Drug Design Expert software version 10. The response surface methodology by a 32-central composite design predicted optimal synthesis parameters for the microspheres to be 295 mg for COM and 219 mg for Na-Alg. An optimized formulation was prepared under these conditions and used to evaluate the micrometric properties, morphology and structural characteristics, swelling behavior, in vitro drug release, and kinetics. Acute toxicity studies were carried out on blank COM/Na-Alg microspheres to deem them safe for in vivo studies. The DEE (%) was calculated to be 85.8 ± 1.67, whereas scanning electron microscopy (SEM) showed a coarse surface with characteristic wrinkles and cracks with an optical microscopic particle size of 0.96 ± 2.45. The ex vivo tests showed great mucoadhesive properties and good swelling behavior with pH-responsive drug release and a significant reduction in in vivo blood glucose levels. The results advocated the use of optimized microspheres to enhance the bioactivity with a possible dose reduction, making it less symptomatic, reducing the expense of the treatment, and subsequently facilitating better patient compliance.

Prunus armeniaca Gum-Alginate Polymeric Microspheres to Enhance the Bioavailability of Tramadol Hydrochloride: Formulation and Evaluation.

Combinations of polymers can improve the functional properties of microspheres to achieve desired therapeutic goals. Hence, the present study aimed to formulate Prunus armeniaca gum (PAG) and sodium alginate microsphere for sustained drug release. Blended and coated microspheres were prepared using the ionotropic gelation technique. The effect of polymer concentration variation was studied on the structural and functional properties of formulated microspheres. FTIR, XRD, and thermal analysis were performed to characterize the microspheres. All the formulations were well-formed spherical beads having an average diameter from 579.23 ± 07.09 to 657.67 ± 08.74 µm. Microspheres entrapped drugs within the range 65.86 ± 0.26-83.74 ± 0.79%. The pH-dependent swelling index of coated formulations was higher than blended. FTIR spectra confirmed the presence of characteristic peaks of entrapped Tramadol hydrochloride showing no drug-polymer interaction. In vitro drug release profile showed sustained release following the Korsmeyer-Peppas kinetic model with an R2 value of 0.9803-0.9966. An acute toxicology study employing the oral route in Swiss albino mice showed no signs of toxicity. It can be inferred from these results that blending PAG with sodium alginate can enhance the stability of alginate microspheres and improve its drug release profile by prolonging the release time.

Synthesis of pH-Sensitive Cross-Linked Basil Seed Gum/Acrylic Acid Hydrogels by Free Radical Copolymerization Technique for Sustained Delivery of Captopril.

The pH-sensitive polymeric matrix of basil seed gum (BSG), with two different monomers, such as acrylic acid (AA) and N, N-Methylene-bis-acrylamide (MBA), was selected to use in hydrogels preparation through a free radical copolymerization technique using potassium per sulfate (KPS) as a cross linker. BSG, AA and MBA were used in multiple ratios to investigate the polymer, monomer and initiator effects on swelling properties and release pattern of captopril. Characterization of formulated hydrogels was done by FTIR, DSC/TGA, XRD and SEM techniques to confirm the stability. The hydrogels were subjected to a variety of tests, including dynamic swelling investigations, drug loading, in vitro drug release, sol-gel analyses and rheological studies. FTIR analysis confirmed that after the polymeric reaction of BSG with the AA monomer, AA chains grafted onto the backbone of BSG. The SEM micrographs illustrated an irregular, rough, and porous form of surface. Gel content was increased by increasing the contents of polymeric gum (BSG) with monomers (AA and MBA). Acidic and basic pH effects highlighted the difference between the swelling properties with BSG and AA on increasing concentration. Kinetic modelling suggested that Korsmeyer Peppas model release pattern was followed by the drug with the non-Fickian diffusion mechanism.

pH Responsive Abelmoschus esculentus Mucilage and Administration of Methotrexate: In-Vitro Antitumor and In-Vivo Toxicity Evaluation.

The rapid progression in biomaterial nanotechnology apprehends the potential of non-toxic and potent polysaccharide delivery modules to overcome oral chemotherapeutic challenges. The present study is aimed to design, fabricate and characterize polysaccharide nanoparticles for methotrexate (MTX) delivery. The nanoparticles (NPs) were prepared by Abelmoschus esculentus mucilage (AEM) and chitosan (CS) by the modified coacervation method, followed by ultra-sonification. The NPs showed much better pharmaceutical properties with a spherical shape and smooth surface of 213.4-254.2 nm with PDI ranging between 0.279-0.485 size with entrapment efficiency varying from 42.08 ± 1.2 to 72.23 ± 2.0. The results revealed NPs to possess positive zeta potential and a low polydispersity index (PDI). The in-vitro drug release showed a sustained release of the drug up to 32 h with pH-dependence. Blank AEM -CS NPs showed no in-vivo toxicity for a time duration of 14 days, accompanied by high cytotoxic effects of optimized MTX loaded NPs against MCF-7 and MD-MBA231 cells by MTT assay. In conclusion, the findings advocated the therapeutic potential of AEM/CS NPs as an efficacious tool, offering a new perspective for pH-responsive routing of anticancer drugs with tumor cells as a target.

Ficus benghalensis as Potential Inhibitor of 5α-Reductase for Hair Growth Promotion: In Vitro, In Silico, and In Vivo Evaluation.

The screening of hair follicles, dermal papilla cells, and keratinocytes through in vitro, in vivo, and histology has previously been reported to combat alopecia. Ficus benghalensis has been used conventionally to cure skin and hair disorders, although its effect on 5α-reductase II is still unknown. Currently, we aim to analyze the phytotherapeutic impact of F. benghalensis leaf extracts (FBLEs) for promoting hair growth in rabbits along with in vitro inhibition of the steroid isozyme 5α-reductase II. The inhibition of 5α-reductase II by FBLEs was assessed by RP-HPLC, using the NADPH cofactor as the reaction initiator and Minoxin (5%) as a positive control. In silico studies were performed using AutoDock Vina to visualize the interaction between 5α-reductase II and the reported phytoconstituents present in FBLEs. Hair growth in female albino rabbits was investigated by applying an oral dose of the FBLE formulation and control drug to the skin once a day. The skin tissues were examined by histology to see hair follicles. Further, FAAS, FTIR, and antioxidants were performed to check the trace elements and secondary metabolites in the FBLEs. The results of RP-HPLC and the binding energies showed that FBLEs reduced the catalytic activity of 5α-reductase II and improved cell proliferation in rabbits. The statistical analysis (p < 0.05 or 0.01) and percentage inhibition (>70%) suggested that hydroalcoholic FBLE has more potential in increasing hair growth by elongating hair follicle's anagen phase. FAAS, FTIR, and antioxidant experiments revealed sufficient concentrations of Zn, Cu, K, and Fe, together with the presence of polyphenols and scavenging activity in FBLE. Overall, we found that FBLEs are potent in stimulating hair follicle maturation by reducing the 5α-reductase II action, so they may serve as a principal choice in de novo drug designing to treat hair loss.

Linum usitatissimum seed mucilage-alginate mucoadhesive microspheres of metformin HCl: Fabrication, characterization and evaluation.

This study investigates the fabrication, characterization and optimization of Linum usitatissimum mucilage (LSM) with sodium alginate mucoadhesive microspheres loaded metformin HCl, a sustained release dosage form prepared by ionic gelation technique. The effect of changing the polymer ratio with drug was studied for drug encapsulation efficiency and in vitro drug release for 12 h. Drug entrapment efficiency of all formulations was in the range of 77.93 ± 3.67 to 92.25 ± 4.08% with sustained release of 80 ± 0.12% to 88 ± 0.33% for 12 h. It followed Korsmeyers Peppas model (R2 = 0.9786-0.9964) with super case II transport mechanism. Average microsphere size of all formulations was within the range of 817-911 µm. SEM, FTIR were also characterized and swelling behavior of microspheres was affected by pH of buffer medium. These microspheres also showed good mucoadhesivity in wash off test. The optimized LSM-alginate mucoadhesive microspheres containing metformin HCl demonstrated significant hypoglycemic effect in alloxan-induced diabetic rats for prolonged period of time.

Terminalia arjuna gum/alginate in situ gel system with prolonged retention time for ophthalmic drug delivery.

Poor availability is the major barrier to accept the new smart gel system as a preferred ophthalmic solution for various eye problems. Smart gel system especially derived from natural source allows the rapid transition of ocular solution into gel form upon contact to tear solution. The present experimental scheme was intended to prepare and characterize a pH triggered in situ gelling system using moxifloxacin HCl (MOX-HCl). Gum was extracted from Terminalia arjuna bark resin and used as gelling agent in blend with sodium alginate. Sterilized formulations were developed and characterized for their physicochemical attributes. These were further investigated for microbiological testing and eye irritation studies. Drug loaded in situ gel was appeared as clear sol that converted into gel phase in presence of tear solution. Optimized formulation was stable, therapeutically efficacious, non-irritant and has a sustained release of the drug for twelve hours period. Instillation of MOX-HCl loaded in situ gel did not cause any type of irritation symptoms like redness, inflammation and excessive tear production in rabbits as compared to control. MOX-HCl loaded in situ gel can be appraised as a substitute for conventional eye drops for extended precorneal retention, improved corneal permeability along with better ocular bioavailability.

Taro-corms mucilage-alginate microspheres for the sustained release of pregabalin: In vitro &in vivo evaluation.

Taro corms mucilage (TCM)-alginate microspheres had been prepared using TCM and alginate as blend and coated form in various ratios through inotropic gelation approach. The prepared microspheres have been of sphere-formed having coarse surface with average particle size within the range 498 µm ±â€¯0.17 to 715 µm ±â€¯0.34. The drug entrapment efficiency was 74.33 ±â€¯0.04% to 89.63 ±â€¯0.01% and swelling of microspheres followed the pattern (blended >coated >plain). FTIR research showed that there had been no interactions among pregabalin and polymers used; these microspheres were further characterized by DSC and XRD. The in vitro drug release followed sustained release (Korsmeyer-Peppas model) pattern (R2 = 0.9552-0.9906) and value of n > 1 showed that drug released by means of anomalous (non-Fickian) diffusion. The in vivo research established that there were highly significant difference with p < 0.001 within the pharmacokinetic parameters (Cmax, t½, AUC0-∞, Ke), while pregabalin microspheres in comparison to pure drug. Therefore, it is concluded that blended microspheres has greater bioavailability for pregabalin with sustained release effect. This evolved that TCM has been proved to be emerging potential pharmaceutical excipient for sustained release drug delivery systems.

The genus Cuscuta (Convolvolaceac): An updated review on indigenous uses, phytochemistry, and pharmacology.

Cuscuta, commonly known as dodder, is a genus of family convolvolaceace. Approximately 170 species of Cuscuta are extensively distributed in temperate and subtropical areas of the world. Species of this genus are widely used as essential constituents in functional foods and traditional medicinal systems. Various parts of many members of Cuscuta have been found efficacious against a variety of diseases. Phytochemical investigations have confirmed presence of biologically active moieties such as flavonoids, alkaloids, lignans, saponines, phenolics, tannins, and fatty acids. Pharmacological studies and traditional uses of these plants have proved that they are effective antibacterial, antioxidant, antiostioporotic, hepatoprotective, anti-inflammatory, antitumor, antipyretic, antihypertensive, analgesic, anti hair fall, and antisteriogenic agents.

Polymeric microspheres of okra mucilage and alginate for the controlled release of oxcarbazepine: In vitro &in vivo evaluation.

Oxcarbazepine-loaded alginate/okra pods mucilage microspheres were prepared through inotropic gelation technique for the sustained release of oxcarbazepine. The drug encapsulating efficiency of these microspheres was found 76.22 ±â€¯0.01% to 90.57 ±â€¯0.02% and their average particle sizes were 496 µm ±â€¯0.41 to 692 µm ±â€¯0.22. These microspheres were characterized in terms of swelling capacity, FTIR, DSC and SEM analysis. The in vitro drug release from these microspheres was followed sustained release (Korsemeyer - Peppas model) pattern (R2 = 0.9552-0.9906) and value of n > 1 showed that drug released by anomalous (non-Fickian) diffusion. The in vivo studies showed that there were highly significant difference with p < 0.001 in the pharmacokinetic parameters (Cmax, t½, AUC0-∞, Ke), when oxcarbazepine was formulated in form of polymeric microspheres as compared to pure drug.

COLOCASIA ESCULENTA CORMS MUCILAGE-ALGINATE MICROSPHERES OF OXCARBAZEPINE: DESIGN, OPTIMIZATION AND EVALUATION.

The present investigation was undertaken with an objective of formulating sustained release microspheres of oxcarbazepine (OXC), an anti-epileptic drug, to overcome poor patient compliance and exposure to high doses associated with currently marketed OXC dosage forms. Ionic gelation technique was used to prepare OXC microspheres by using sodium alginate along with rate controlling polymer Colocasia esculenta mucilage (CEM) matrix as well coated form. The microspheres have been characterized by differential scanning calorimetry (DSC) for understanding thermal stability and Fourier transform infrared (FT-IR) spectroscopy to investigate the chemical interaction as well as to assess the structure of drug-loaded formulation. Surface morphology of the microspheres was investigated by scanning electron microscope (SEM). The size distribution of OXC microspheres as studied by optical microscopy was in the range of 394-575 pm. The microspheres exhibited encapsulating efficiency from 75 to 92%. The release of drug from the microspheres at pH 1.2 is negligible. Under neutral conditions, the microspheres were swell and release was attributed mainly to polymer relaxation. The release pattern from microspheres followed Korsmeyer-Peppas model and the value of n > 1 showed that drug released by anomalous (non-Fickian) diffusion. The data obtained thus suggest that a microparticulate system can be successfully designed by using CEM with alginate for sustained delivery of OXC.

Effect of Skimmed Milk on the Absorption and Metabolism of5-Fluorouracil (5-FU) in Animals.

Several modalities of drug administration have been investigated to improve bioavailability and to reduce 5-FU related toxicity. The aim of present study was to evaluate the effect of skimmed milk on the absorption and metabolism of 5-FU in rabbits, mice and dogs. It was further aimed to determine its route related toxicity in rabbits. Plasma concentration of both 5-FU and its metabolite 5-Fluoro-2-deoxyuridine (5-Fdurd) was determined using HPLC. The absorption of 5-FU co-administered with skimmed milk was significantly higher as compared to its co-administration with water in rabbits and mice (p < 0.001), whereas no significant difference was observed in dogs. The plasma concentration of 5-Fdurd a major metabolite of 5-FU was significantly higher in water group when compared with skimmed milk group in rabbits and mice (p < 0.05), whereas no significant difference was observed in dogs. Route related toxicity was also determined in rabbits. Various hematological parameters were studied at 4(th) and 7(th) day after oral and intravenous administration of 5-FU. WBCs count was significantly decreased in intravenous group as compared to control and oral groups (p < 0.001). It was concluded that co-administration of skimmed milk with 5-FU increases its absorption and reduces its metabolism. Skimmed milk also reduces 5-FU related toxicity in rabbits.