Mutual Prodrug Research Articles

Propyphenazone-based analogues as prodrugs and selective cyclooxygenase-2 inhibitors.

Improving the gastrointestinal safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) is an important goal. Herein, we report two strategies, using the nonacidic propyphenazone structure, with potential to overcome the side effects of NSAIDs. Propyphenazone was employed to temporarily mask the free acid group of the widely used NSAIDs ibuprofen, diclofenac, and ketoprofen to develop three mutual prodrugs hypothesized to have minimal GI irritation. The three prodrugs exhibit in vivo anti-inflammatory and analgesic activities with improved potency over each parent drug when compared to a nonhydrolyzable control betahistine-propyphenazone (BET-MP). Additionally, ANT-MP formed by the irreversible coupling of propyphenazone and 4-aminoantipyrine, displayed exceptional COXII selectivity (COXII IC50 of 0.97 ± 0.04 μM, compared to no observed inhibition of COXI at 160 μM). Inhibition of COXII suppresses inflammatory diseases without affecting COXI-mediated GI tract events. ANT-MP exhibited maximal analgesic effect when tested in vivo in an abdominal writhing assay (100% protection) and its anti-inflammatory activity showed a peak at 2 h in a carrageenan-induced paw edema model. Its unique selectivity toward the COXII enzyme was investigated using molecular modeling techniques.

Salicylanilide pyrazinoates inhibit in vitro multidrug-resistant Mycobacterium tuberculosis strains, atypical mycobacteria and isocitrate lyase

The development of antimicrobial agents represents an up-to-date topic. This study investigated in vitro antimycobacterial activity, mycobacterial isocitrate lyase inhibition and cytotoxicity of salicylanilide pyrazinoates. They may be considered being mutual prodrugs of both antimycobacterial active salicylanilides and pyrazinoic acid (POA), an active metabolite of pyrazinamide, in which these esters are likely hydrolysed without presence of pyrazinamidase/nicotinamidase. Minimum inhibitory concentrations (MICs) of the esters were within the range 0.5–8μmol/l for Mycobacterium tuberculosis and 1–32μmol/l for nontuberculous mycobacteria (Mycobacterium avium, Mycobacterium kansasii). All esters showed a weak inhibition (8–17%) of isocitrate lyase at the concentration of 10μmol/l. The most active pyrazinoates showed MICs for multidrug-resistant tuberculosis strains in the range of 0.125–2μmol/l and no cross-resistance with clinically used drugs, thus being the most in vitro efficacious salicylanilide esters with 4-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate superiority (MICs⩽0.25μmol/l). This promising activity is likely due to an additive or synergistic effect of released POA and salicylanilides. Selectivity indexes for the most active salicylanilide pyrazinoates ranged up to 64, making some derivatives being attractive candidates for the next research; 4-bromo-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate showed the most convenient toxicity profile.

Carrier-linked mutual prodrugs of biphenylacetic acid as a promising alternative to bioprecursor fenbufen: design, kinetics, and pharmacological studies

Novel mutual prodrugs of biphenylacetic acid were designed as a promising gastro-protective alternative to fenbufen. Biphenyacetic acid was covalently linked with two non-essential amino acids (D-phenylalanine and glycine) possessing wound healing, analgesic, and anti-inflammatory properties. The prodrugs exhibited good stability in stomach homogenates while hydrolytic release of biphenylacetic acid was observed in phosphate buffer, small intestinal homogenates, and 80% human plasma. In vivo behavior of prodrugs on oral administration to Wistar rats demonstrated 33-45% release of biphenylacetic acid in blood over a period of 24 h indicating passage of intact prodrugs to colon, colonic release of parent drug followed by its absorption through colonic mucosa into systemic circulation. Prodrugs were extensively evaluated for analgesic, anti-inflammatory, anti-arthritic, and ulcerogenic activities. Biochemical, haemetological, histopathological, and radiological studies were also performed. Conversion of bioprecusor fenbufen into mutual carrier-linked prodrugs proved to be promising alternative in terms of reduced ulcerogenic propensity, longer duration of analgesia, enhanced/prolonged anti-inflammatory activity, and superior anti-arthritic effect. These prodrugs could be developed further for chronotherapy of rheumatoid arthritis.

Synthesis, docking and in-vitro screening of mannich bases of thiosemicarbazide for anti-fungal activity

Mannich bases and thiosemicarbazide individually show antimicrobial, antifungal, anticonvulsant, antimalarial, analgesic and anti-inflammatory type of varied pharmacological activities. The novelty of the present work is the synthesis of mannich bases of thiosemicarbazide as mutual prodrugs. In step-1, mannich bases are synthesized using aldehyde, ketones and amines with aliphatic, aromatic, cyclic and heterocyclic nature. In step-2, the synthesized bases were condensed with thiosemicarbazide to form mannich bases of thiosemicarbazide. Structural characterization of synthesized compounds was done using IR, mass and H-NMR spectroscopy. The compounds were screened for anti-fungal activity using BHI (brain heart infusion) broth dilution method against Candida albicans and Apergillus niger. Docking of synthesized compounds was done on CYP51A1, P45014DM (Lanosterol 14 α-demethylase enzyme) using Vlife MDS 3.5 to conform the mechanism of antifungal activity. Docking study showed a strong hydrophobic interaction between amino acid residues Arganine (ARG141), Glutamine (GLU146), Leucine (LEU54), Lycine (LYC227), and Threonine (THR147) with the carbon of ketone, nitrogen of amine and sulfur of thiosemicarbazide. Strong Vander wall’s interactions are also observed with the carbon of ketone, nitrogen of amine and sulfur of thiosemicarbazide.Analogs with aromatic and substituted aromatic aldehydes showed least activity, while analogs with aliphatic aldehyde, ketones and amines showed greater activity in C. albicans compared to A. niger. Analogs having morpholine as amine showed comparable activity in both. Compounds K17, K18, K19, and K20 have shown comparable highest activities.

Synthesis, biological activities, and pharmacokinetics studies of a mutual prodrug of aceclofenac and paracetamol

An ester-based mutual prodrug (aceclofenac–paracetamol; AC-PR) was synthesized (one-pot method) with an aim of improving the therapeutic index through prevention of gastrointestinal irritation and bleeding that is associated with aceclofenac. The release of aceclofenac and paracetamol from the ester prodrug (AC-PR) was studied by reverse phase HPLC in hydrochloric acid buffer (pH 1.2), phosphate buffer (pH 7.4), 80 % v/v human plasma, 10 % w/v rat intestinal homogenate and 10 % w/v rat liver homogenate (pH 7.4). The prodrug showed negligible hydrolysis at pH 1.2 as compared to pH 7.4, suggesting that very less of the prodrug would hydrolyze in stomach, but would release the parent drugs at pH 7.4 in adequate amounts. The prodrug showed enhanced anti-inflammatory activity and significant protection against acetic acid-induced writhings (analgesic activity) as compared to that of aceclofenac. Further, the prodrug produced reduced number of ulcers as compared to that of the parent drug. These results suggest that the synthesized mutual prodrug (AC-PR) is better in terms of activity and GIT toxicity than the parent drug.

Mutual prodrugs containing bio-cleavable and drug releasable disulfide linkers

We report herein the design and synthesis of several representative examples of novel mutual prodrugs containing nine distinct types of self-immolative drug-releasable disulfide linkers with urethane, ester, carbonate, or imide linkages between the linker and any two amine/amide/urea (primary or secondary) or carboxyl or hydroxyl (including phenolic)-containing drugs. We also report drug release profiles of a few representative mutual prodrugs in biological fluids such as simulated gastric fluid and human plasma. We also propose plausible mechanisms of drug release from these mutual prodrugs. We have also conducted a few mechanistic studies based on suggested sulfhydryl-assisted cleavage of mutual prodrugs and characterized a few important metabolites to give support to the proposed mechanism of drug release from the reported mutual prodrugs.

Disease-Modifying Effect of Anthraquinone Prodrug with Boswellic Acid on Collagenase-Induced Osteoarthritis in Wistar Rats

Diacerein and its active metabolite rhein are promising disease modifying agents for osteoarthritis (OA). Boswellic acid is an active ingredient of Gugglu; a herbal medicine commonly administered in osteoarthritis. Both of them possess excellent anti-inflammatory and anti-arthritic activities. It was thought interesting to conjugate rhein and boswellic acid into a mutual prodrug (DSRB) and evaluate its efficacy on collagenase-induced osteoarthritis in rats wherein the conjugate, rhein, boswellic acid and their physical mixture, were tested based on various parameters. Oral administration of 3.85 mg of rhein, 12.36 mg of boswellic acid and 15.73 mg of DSRB which would release equimolar amounts of rhein and boswellic acid, exhibited significant restoration in rat body weight as compared to the untreated arthritic control group. Increase in knee diameter (mm), due to edema was observed in group injected with collagenase, which reduced significantly with the treatment of conjugate. The hematological parameters (Hb, RBC, WBC and ESR) and biochemical parameters (CRP, SALP, SGOT and SGPT) in the osteoarthritic rats were significantly brought back to normal values on treatment with conjugate. It also showed better anti-ulcer activity than rhein. Further the histopathological studies revealed significant anti-arthritic activity of conjugate when compared with the arthritic control group. In conclusion, the conjugate at the specified dose level of 15.73 mg/kg, p. o. (BID) showed reduction in knee diameter and it could significantly normalize the hematological and biochemical abnormalities in collagenase-induced osteoarthritis in rats. Further the histopathological studies confirmed the additive anti-arthritic effect of DSRB as compared to plain rhein.

Design, Synthesis and Preliminary Pharmacological Evaluation of Mutual Prodrug of Non-Steroidal Anti-Inflammatory Drugs Coupling With Natural Anti-Oxidants Via Glycine

Non-steroidal anti-inflammatory drugs (NSAIDs); naproxen and indomethacin have been conjugated with different antioxidants (thymol, menthol & guaiacol) having antiulcerogenic activity via glycine amino acid as spacer with the objective of obtaining NSAIDs-glycine- antioxidant prodrugs as gastrosparing NSAIDs devoid of ulcerogenic side effects and synergistically with anti-inflammatory action of glycine. Four mutual prodrugs (IIV) were synthesized using glycine as spacer and their structures were confirmed and characterized using elemental microanalysis (CHNO), IR, and some physiochemical properties.Invivo acute anti-inflammatory activity of the compounds (I & II) (naproxen derivatives) and the compounds (III & IV) (indomethacin derivatives) was evaluated in rat using an egg-white induced edema model of inflammation in a dose equivalent to 2.5 mg/Kg of naproxen, and 2 mg/Kg of indomethacin respectively.All tested compounds produced significant reduction of paw edema with respect to the effect of propylene glycol 50% v/v (control group). Moreover, the activity of compound III was significantly higher than that of indomethacin (at 2 mg/Kg), while compound IV expressed a comparable effect to that of indomethacin in the (120–300) minute time of the experiment, while compounds I&II was showed a comparable effect to that of naproxen at (180-300) minute time interval of the experiment. The result of this study indicates that these mutual prodrugs of naproxen & indomethacin maintained or may enhanced their antiinflammatory activity.

SYNTHESIS AND EVALUATION OF MUTUAL PRODRUG OF ASPIRIN AND CHLORZOXAZONE

Aspirin chlorzoxazone ester linked mutual prodrug was synthesized with the aim of improving the thera peutic index through prevention of gastrointestinal irritation and bleeding. The structure of the synthesized ester prodrug was con firmed by IR and 1H NMR spectroscopy and their purity was established by elemental analysis, HPLC and TLC. The release of ASP as well as CZX, from the ester prodrug was studied. A validated analytical HPLC method for the estimat ion of the ASP , and the pr odrug was developed. The kinetics of ester hydrolysis was studied in four different non - enzymatic buffer solutions, at pH 3 , 4, 5 and 7.4 as well as in experimental plasma . Study of skeletal muscle relaxant and anti - in flammatory properties in comparison wit h the reference compounds has shown that both skeletal muscle relaxant and anti - in flammatory activities were present at the same doses of the investigated compounds. The ester was found to be less irritating to gastric mucosal membrane than the parent drugs . These results sugge st that the synthesized prodrug is characterized by better therapeutic index than the parent drugs.

Synthesis, characterization, in vitro hydrolysis and pharmacodynamic profiles of potential novel mutual prodrugs of N-(2,3-xylyl anthranilic acid)

In present research work, we report the synthesis, in vitro hydrolysis study and pharmacological evaluation of new mutual prodrugs of mefenamic acid (MA) and 1,2 dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenylpyrazol-3-one with the aim of improving the therapeutic potency and retard the adverse effects of gastrointestinal origin. The structure of the synthesized mutual ester prodrugs (MP1 and MP2) were confirmed by IR, 1H NMR, 13C NMR, mass spectroscopy and their formation was confirmed by TLC. The purity of the synthesized compounds was established by elemental analysis. The title compounds were tested for analgesic activity by acetic acid-induced writhing method; anti-inflammatory activity was tested by carrageenan-induced rat paw edema method and ulcerogenicity. The study of the analgesic activity revealed that both prodrugs (MP1 and MP2) have shown significant reduction (81.67, 63.90 %) in writhing response produced by acetic acid as compared to parent drug MA (61.10 %). Both mutual prodrugs showed better maximum anti-inflammatory effects (71.43, 85.71 %) and for longer time as compared to parent drug MA (53.14 %). The synthesized prodrugs were also found to be very less irritating to gastric mucosal membrane than parent drugs. The kinetics of ester hydrolysis was studied in simulated gastric fluid (SGF) at pH 1.2 and simulated intestinal fluid (SIF) at pH 7.4. The release of free MA from prodrugs showed negligible hydrolysis in SGF as compared to SIF. This indicated that prodrugs were sufficiently stable at pH 1.2 and do not break in the stomach, but release MA in SIF.

A FACILE SYNTHESIS OF MUTUAL PRODRUG OF DICLOFENAC SODIUM AND PARACETAMOL AND ITS PREFORMULATION STUDIES

Mutual prodrug was synthesized by esterifying diclofenac with paracetamol. In vitro hydrolysis of prodrug in HCl buffer (pH 1.2) and phosphate buffer (pH 7.4) showed that the drug was released more in pH 7.4. The purity of the prodrug was confirmed by TLC and characterized on the basis of IR spectroscopy and 1H NMR spectroscopy. The physiochemical parameters were determined and the results showed that they are more lipophilic than the parent drug. The compound was also evaluated for anti-inflammatory and ulcerogenicity.

Design, synthesis and hydrolytic behavior of mutual prodrugs of NSAIDs with gabapentin using glycol spacers.

The free –COOH present in NSAIDs is thought to be responsible for the GI irritation associated with all traditional NSAIDs. Exploitation of mutual prodrugs is an approach wherein the NSAID is covalently bounded to a second pharmacologically active carrier/drug with the ultimate aim of reducing the gastric irritation. In this study some NSAIDs were conjugated with gabapentin via ester bonds using glycol spacers with the expectation of reducing gastric adverse effects and obtaining synergistic analgesic effects. The kinetics of ester hydrolysis were studied in two different non enzymatic buffer solutions at pH 1.2 and 7.4, as well as in 80% human plasma using HPLC with chloroform -methanol as mobile phase. Compounds 9a–c with ethylene glycol spacers showed significant stability at buffer solutions with half lives ranging from about 8–25 h, while the underwent a reasonable plasma hydrolysis (49%–88%) in 2 h. Compound 9d with a propylene glycol spacer shows a higher rate of enzymatic hydrolysis than the corresponding ethylene glycol compound 9c. The result of compounds 9a-c indicate that these compounds may be stable during their passage through the GIT until reaching the blood circulation.

Synthesis and pharmacokinetic profile of rhein- boswellic acid conjugate

Rhein, an active metabolite of diacerein, down-regulates the gene-expression and production of pro-matrix metalloproteinases and up-regulates the tissue inhibitors of metalloproteinase-1 production. The therapeutic effects of diacerein on osteoarthritis are, at least in part, due to the chondroprotective effect of rhein. Boswellic acid is a specific, non-redox inhibitor of leukotriene synthesis. It is claimed to possess good anti-inflammatory, anti-arthritic, analgesic, and anti-ulcer activities. It prevents the destruction of articular cartilage by decreasing degradation of glycosaminoglycans. Therefore, rhein and boswellic acid were linked chemically through a bioreversible ester linkage to synthesize their mutual prodrug by reported procedure. In vitro release profile of this prodrug was extensively studied in aqueous buffers of varied pH, upper GIT homogenates and 80% human plasma. In vivo release studies were undertaken in blood, urine and feces of rats. The prodrug was stable in HCl buffer (pH 1.2) and stomach homogenates of rats. However; in phosphate buffer (pH 7.4) and in intestinal homogenates the prodrug exhibited 91% and 96% release of rhein and 27.5% and 38% release of boswellic acid respectively over a period of 6h following first order kinetics. In 80% human plasma (in vitro) and rat blood (in vivo) also 96.35% and 91% release of rhein and 78% and 86.41% release of boswellic acid respectively was observed. The 24h pooled samples of rat urine revealed presence of 6.2% intact prodrug, 7.1% of rhein and 8.9% of boswellic acid indicating their renal excretion. Samples of rat feces pooled over a period of 24h showed absence of rhein and presence of 3.1% of intact boswellic acid and 4.6% of boswellic acid emphasizing their intestinal excretion. The in vivo release kinetics of prodrug in rat clearly indicated activation of prodrug to be occurring in blood, being catalyzed by the weak alkaline pH of blood (7.4) in combination with esterases present therein.

Synthesis and evaluation of mutual prodrugs of ibuprofen with menthol, thymol and eugenol

The present works deals with simple and efficient method of improving therapeutic efficacy of racemic ibuprofen by retarding gastrointestinal side effects through masking of carboxylic group chemically. This is achieved by synthesis and evaluation of ester derivatives of ibuprofen as mutual prodrugs with naturally occurring phenolic and alcoholic compounds. Promoieties like menthol; thymol and eugenol were selected with the aim of getting synergistic effect as these are natural analgesic having traditional medicinal values. Prodrugs are found to be highly lipophilic as compared to parent drug. All the prodrugs are found to be highly stable at acidic pH while undergoes hydrolysis at neutral and alkaline pH as indicated by their t1/2 values. Synthesized prodrugs derivatives show increased anti-inflammatory activity that might be attributed to synergistic effect as ibuprofen conjugates to natural analgesics. Ulcer index shows much reduction in gastric ulceration compared to ibuprofen concluding the successful masking of acidic group.

A multifunctional 5-aminolevulinic acid derivative induces erythroid differentiation of K562 human erythroleukemic cells

Anemia is a major clinical symptom of a wide variety of pathological conditions a common related to reduced erythropoiesis. Whereas erythropoietin treatment showed an improvement in the patients’ condition, it revealed increased risks of thromboembolic and cardiovascular events. Herein we describe stimulation of erythropoiesis by the multifunctional 1-(butyryloxy)ethyl-5-amino-4-oxopentanoate, (AlaAcBu), a 5-aminolevulinic-acid (ALA) derivative, which undergoes metabolic hydrolysis yielding two erythroid differentiation inducers, ALA and butyric acid (BA), each acting through a different mechanism. ALA, the first precursor in the heme biosynthesis, accelerates heme synthesis and BA, a histone deacetylase inhibitor (HDACI) that activates the transcription of globin mRNA.Our results show that the AlaAcBu mutual prodrug is a potent chemical differentiation inducer of K562 human erythroleukemia cells manifested by augmentation of heme and globin synthesis and assembly of hemoglobin. Exposure of K-562 cells to AlaAcBu resulted in an increase in heme synthesis and globin expression. Stimulation of the heme pathway was evident by the over-expression of porphobilinogen deaminase (PBGD) and ferrochelatase. AlaAcBu promoted cellular erythroid differentiation depicted by the expression of the marker glycophorin A and cellular maturation characterized by cytoplasm hemoglobinization, polar arrangement of mitochondria and a developed central vacuolar system preceding nuclear extrusion. The ability of AlaAcBu to promote differentiation along the erythroid lineage and to dramatically induce hemoglobin synthesis presented in this report.

TFAA-H3PO4 mediated rapid and single-step synthesis of mutual prodrugs of paracetamol and NSAIDs

A clean and operationally simple method has been developed for the preparation of mutual prodrug using paracetamol and various nonsteroidal anti-inflammatory drugs. The methodology involves use of TFAA/H3PO4 in acetonitrile and a variety of mutual prodrugs has been prepared in good yields by using this single-step C–O bond forming reaction.

Evaluation of mefenamic acid mutual prodrugs

Mutual prodrugs consisting of mefenamic acid with menthol and thymol have been synthesized as a gastrosparing NSAIDs, devoid of ulcerogenic side effects. The structures of synthesized esters were confirmed by IR, 1H NMR, and mass spectroscopy. The kinetics of ester hydrolysis was studied in nonenzymatic buffer solutions, at pH 2 and 7.4 as well as in human plasma by HPLC. Its anti-inflammatory, analgesic, and ulcerogenic activities were evaluated. Then biochemical parameters (GWM and Hexosamine), oxidative parameters (LPO, GSH, CAT, and SOD), and protein estimation was also done. The results indicated that synthesized prodrugs are chemically stable, biolabile, and posses optimum lipophilicity. The synthesized prodrugs are characterized by better ulcer index than the parent drug.

Synthesis and in vitro kinetic study of novel mutual azo prodrug for inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) refers to idiopathic inflammatory diseases of the intestine, principally ulcerative colitis and Crohn’s disease. IBD is characterized by chronic inflammation in the mucosal membrane of large intestine. 5ASA is the gold standard for the treatment of IBD and when searched for a better 5ASA prodrug, a novel mutual azo prodrug was designed and synthesized. Methods: A mutual prodrug was synthesized by coupling p-phenetidine with salicylic acid. The stability of this prodrug in HCl buffer, in phosphate buffer and in rat fecal matter were monitored. Results: The chemical structure of mutual prodrug was characterized by physical and spectroscopic techniques using FTIR, UV/Visible, 1 H-NMR and 13 C-NMR spectra. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-ASA and p-phenetidine, whereas in phosphate buffer (pH 7.4) only (22.04 %) release was observed over a period of (6 hr.). In rat fecal matter, the hydrolysis of mutual prodrug was almost complete (77.96 %), with a half-life of 182.67 min, following zero order kinetics. Conclusion: The mutual prodrug was split in colon by the action of bacterial azoreductase into 5-ASA and p-phenetidine that constitute two anti-inflammatory compounds with different mechanisms of action. Therefore, this mutual prodrug is a promising colon specific prodrug for IBD and worthy of further study.

Synthesis of Mutual Azo Prodrugs of Anti-inflammatory Agents and Peptides Facilitated by α-Aminoisobutyric Acid

Reported is the synthesis of azo mutual prodrugs of the nonsteroidal anti-inflammatory agents (NSAIDs) 4-aminophenylacetic acid (4-APAA) or 5-aminosalicylic acid (5-ASA) with peptides, including an antibiotic peptide temporin analogue modified at the amino terminal by an α-aminoisobutyric acid (Aib) residue. These prodrugs are designed for colonic delivery of two agents to treat infection and inflammation by the bacterial pathogen Clostridium difficile .

Chitosan Derivatives with Antimicrobial, Antitumour and Antioxidant Activities - a Review

Chitosan is a linear polysaccharide with a good biodegradability, biocompatibility, and no toxicity, which provide it with huge potential for future development. The chitosan molecule appears to be a suitable polymeric complex for many biomedical applications. This review gathers current findings on the antibacterial, antifungal, antitumour and antioxidant activities of chitosan derivatives and concurs with our previous review presenting data collected up to 2008. Antibacterial activity is based on molecular weight, the degree of deacetylation, the type of substitutents, which can be cationic or easily form cations, and the type of bacterium. In general, high molecular weight chitosan cannot pass through cell membranes and forms a film that protects cells against nutrient transport through the microbial cell membrane. Low molecular weight chitosan derivatives are water soluble and can better incorporate the active molecule into the cell. Gram-negative bacteria, often represented by Escherichia coli, have an anionic bacterial surface on which cationic chitosan derivatives interact electrostatically. Thus, many chitosan conjugates have cationic components such as ammonium, pyridinium or piperazinium substituents introduced into their molecules to increase their positive charge. Gram-positive bacteria like Staphylococcus aureus are inhibited by the binding of lower molecular weight chitosan derivatives to DNA or RNA. Chitosan nanoparticles exhibit an increase in loading capacity and efficacy. Antitumour active compounds such as doxorubicin, paclitaxel, docetaxel and norcantharidin are used as drug carriers. It is evident that chitosan, with its low molecular weight, is a useful carrier for molecular drugs requiring targeted delivery. The antioxidant scavenging activity of chitosan has been established by the strong hydrogen-donating ability of chitosan. The low molecular weight and greater degree of quarternization have a positive influence on the antioxidant activity of chitosan. Phenolic and polyphenolic compounds with antioxidant effects are condensed with chitosan to form mutual prodrugs.