Mucoadhesive chitosan-coated liposomes: characteristics and stability

Lecithin liposomes, empty or containing FITC-dextran, were prepared by the ethanol injection method. Three different types of chitosans with different molecular weight and degrees of deacetylation were used (Seacure 113, 210 and 311). Chitosan coating was carried out by mixing the liposomal suspension with the chitosan solution followed by incubation. The size of liposomes was measured before and after polymer coating by an image analysis technique. The mean diameter of liposomes containing FITC-dextran was in the size range 250-280nm, whereas the size after coating was 300-330nm, regardless of chitosan type. All chitosan-coated liposomes were of spherical shape and no morphological differences between uncoated and coated liposomes were observed. Liposomes with FITC-dextran, originally entrapping 50% of the marker substance taken in the preparation and coated in the presence of unentrapped marker substance, contained 60-65%of the marker substance. The highest entrapment was found for liposomes coated with medium molecular weight chitosan. The stability of chitosan-coated liposomes in simulated gastric fluid was significantly higher as compared to uncoated liposomes. One can conclude that chitosan is stabilizing the original liposomal structure and protecting liposomally entrapped drug.     

小鼠口服多糖包覆胰岛素脂质体的降血糖作用小鼠口服多糖包覆胰岛素脂质体的降血糖作用

目的 研究壳聚糖和海藻酸钠两种多糖包覆胰岛素脂质体的小鼠po降血糖作用。方法 用逆相蒸发法制备胰岛素脂质体;用透射电镜和激光粒度仪测定它们的形态和粒径;用HPLC法和超速离心法测定包封率;用胃蛋白酶和胰蛋白酶溶液试验多糖包覆脂质体对胰岛素的保护作用;用酶-苯酚法测定小鼠po多糖包覆胰岛素脂质体后降血糖作用。结果小鼠po 0.1%壳聚糖和0.1%海藻酸钠包覆的胰岛素脂质体具有较好的降血糖作用。结论壳聚糖或海藻酸钠包覆的脂质体能减少胃蛋白酶或胰蛋白酶对胰岛素的降解并促进胰岛素po吸收。     

Development and characterization of polymer-coated liposomes for vaginal delivery of sildenafil citrate

Vaginal administration of sildenafil citrate has shown recently to develop efficiently the uterine lining with subsequent successful embryo implantation following in vitro fertilization. The aim of the present study was to develop sildenafil-loaded liposomes coated with bioadhesive polymers for enhanced vaginal retention and improved drug permeation. Three liposomal formulae were prepared by thin-film method using different phospholipid:cholesterol ratios. The optimal liposomal formulation was coated with bioadhesive polymers (chitosan and HPMC). A marked increase in liposomal size and zeta potential was observed for all coated liposomal formulations. HPMC-coated liposomes showed the greater bioadhesion and higher entrapment efficiency than chitosan-coated formulae. The in vitro release studies showed prolonged release of sildenafil from coated liposomes as compared to uncoated liposomes and sildenafil solution. Ex vivo permeation study revealed the enhanced permeation of coated relative to uncoated liposomes. Chitosan-coated formula demonstrated highest drug permeation and was thus selected for further investigations. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the successful coating of the liposomes by chitosan. Histopathological in vivo testing proved the efficacy of chitosan-coated liposomes to improve blood flow to the vaginal endometrium and to increase endometrial thickness. Chitosan-coated liposomes can be considered as potential novel drug delivery system intended for the vaginal administration of sildenafil, which would prolong system's retention at the vaginal site and enhance the permeation of sildenafil to uterine blood circulation.     

Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice

INTRODUCTION In the past two decades the potential usefulnessof liposomes as drug carriers for improving enteral ab-sorption of poorly absorbed drugs including peptidedrugs such as insulin has attracted considerable interest.These phospholipid vesicles are capable of encapsulat-ing both hydrophobic and hydrophilic drugs; they arebiodegradable and are not toxic in vivo. The drugsencapsulated in liposomes are sufficiently protectedfrom enzymatic attack and immune recognition[1]. Li-po…     

The effect of particle structure of chitosan-coated liposomes and type of chitosan on oral delivery of calcitonin

To optimize the properties of chitosan-coated liposomes for oral administration of peptide drugs, we examined the effect of type of chitosan and the structure of liposomal systems on the mucoadhesiveness of liposomes and resultant pharmacological effects of the liposomal peptide drug. A low-molecular weight chitosan (LCS) and a high-molecular weight chitosan (CS) were used as coating polymers of liposomes containing elcatonin (eCT). The muco-penetrative behaviors across the mucous gel layer covering the intestinal epithelial cells and the pharmacological effect after intragastric administration were determined in rats. The results showed that both LCS-coated liposomes (LCS-Lips) and CS-coated liposomes (CS-Lips) could permeate the mucous layer in the small intestine. The most interesting result was that LCS-Lips containing eCT showed remarkably more prolonged effectiveness in decreasing the blood calcium concentration than did CS-Lips containing eCT, moreover, it was also found that LCS had more efficiency to protect eCT from the enzymatic degradation than CS. In comparing the area above the plasma calcium concentration time curves (AAC) values among eCT-containing liposomes with different structures, i.e. eCT adsorbed on coated liposomes (eCT-ad-CS-Lip, eCT-ad-LCS-Lips) and eCT encapsulated in coated liposomes (eCT-encap-CS-Lips, eCT-encap-LCS-Lips), eCT-encap-CS-Lip showed much higher effectiveness than eCT-ad-CS-Lip. However, the AAC value for eCT-ad-LCS-Lip was comparable to that for eCT-encap-CS-Lip, while the value for eCT-ad-CS-Lip was nearly zero. These results suggested that LCS is a good mucoadhesive polymer candidate for enhancing the bioavailability of orally administered peptide containing liposomes, while encapsulation of eCT within the liposomal particles is important to protect eCT against enzymatic degradation in the gastrointestinal (GI) tract.     

The effect of particle structure of chitosan-coated liposomes and type of chitosan on oral delivery of calcitonin

To optimize the properties of chitosan-coated liposomes for oral administration of peptide drugs, we examined the effect of type of chitosan and the structure of liposomal systems on the mucoadhesiveness of liposomes and resultant pharmacological effects of the liposomal peptide drug. A low-molecular weight chitosan (LCS) and a high-molecular weight chitosan (CS) were used as coating polymers of liposomes containing elcatonin (eCT). The muco-penetrative behaviors across the mucous gel layer covering the intestinal epithelial cells and the pharmacological effect after intragastric administration were determined in rats. The results showed that both LCS-coated liposomes (LCS-Lips) and CS-coated liposomes (CS-Lips) could permeate the mucous layer in the small intestine. The most interesting result was that LCS-Lips containing eCT showed remarkably more prolonged effectiveness in decreasing the blood calcium concentration than did CS-Lips containing eCT, moreover, it was also found that LCS had more efficiency to protect eCT from the enzymatic degradation than CS. In comparing the area above the plasma calcium concentration time curves (AAC) values among eCT-containing liposomes with different structures, i.e. eCT adsorbed on coated liposomes (eCT-ad-CS-Lip, eCT-ad-LCS-Lips) and eCT encapsulated in coated liposomes (eCT-encap-CS-Lips, eCT-encap-LCS-Lips), eCT-encap-CS-Lip showed much higher effectiveness than eCT-ad-CS-Lip. However, the AAC value for eCT-ad-LCS-Lip was comparable to that for eCT-encap-CS-Lip, while the value for eCT-ad-CS-Lip was nearly zero. These results suggested that LCS is a good mucoadhesive polymer candidate for enhancing the bioavailability of orally administered peptide containing liposomes, while encapsulation of eCT within the liposomal particles is important to protect eCT against enzymatic degradation in the gastrointestinal (GI) tract.     

The intracellular uptake ability of chitosan-coated Poly (D,L-lactideco-glycolide) nanoparticles

In this study, we prepared chitosan-coated Poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles. Specifically, we utilized a double emulsion-solvent evaporation technique to formulate nanoparticles containing paclitaxel as a model macromolecule and 6-coumarin as a fluorescent marker. SEM images verified that all nanoparticles were spherical in shape with smooth surfaces. Chitosan coating slightly increased the size distribution of the PLGA/PVA nanoparticles, from 202.2+/-3.2 nm to 212.2+/-2.9 nm, but the encapsulation efficiency was not significantly different. In contrast, coating with chitosan slowed the in vitro drug release rate and significantly changed the zeta potential from negative (-30.1+/-0.6 mV) to positive (26+/-1.2 mV). At the initial burst time, the drug release rate from chitosancoated nanoparticles was slightly slower than that of the uncoated nanoparticles. Chitosan-coated nanoparticles were also taken up much more efficiently than uncoated nanoparticles. This study demonstrated the efficacy of chitosancoated PLGA nanoparticles as an efficient delivery system.     

High efficiency entrapment of superoxide dismutase into mucoadhesive chitosan-coated liposomes

Superoxide dismutase (SOD), antioxidative enzyme and potential anti-inflammatory agent, was encapsulated into mucoadhesive chitosan-coated liposomes in order to increase its releasing time and to facilitate its cellular penetration. Positively, neutrally and negatively charged liposomes were prepared using soybean lecithin, stearylamine, phosphatidyl glycerol and cholesterol. The effects of liposomal lipid composition and protein to lipid ratio on the encapsulation parameters were studied in three preparation methods: dehydration–rehydration, hydration and proliposome methods. The highest efficiency of SOD entrapment, 39–65%, was achieved by the proliposome method. Vesicles prepared by the hydration method entrapped 1–13% and vesicles prepared by dehydration–rehydration entrapped 2–3% of SOD. Stability tests for SOD-loaded liposomes prepared by the proliposome method showed no significant loss of the enzyme activity within 1 month at 4 °C or within 2 days at 37 °C. Positively, neutrally and negatively charged liposomes, prepared by the proliposome method, were successfully coated with two types of low and medium molecular weight chitosans. Both types of chitosan coating increased the mucoadhesive characteristics of all three types of vesicles. Using the proliposome method and subsequent chitosan coating, highly efficient SOD-loaded vesicles for drug targeting on mucosal tissues could be produced.     

Properties of liposomes coated with hydrophobically modified chitosan in oral liposomal drug delivery

Chitosan (CS) has been widely used as an adhesive coating polymer for oral liposomal drug delivery systems because of its adhesive properties on mucous layers. The coating mechanism or interaction of chitosan and liposomes or mucin mainly depends on electrostatic forces. Thus, to enhance the adhesive properties of chitosan, a hydrophobically modified chitosan, i.e., dodecylated chitosan (DC), was synthesized. BIACORE results showed that both CS and DC could interact with mucin. Differences in sensorgram patterns between chitosan-mucin and dodecylated chitosan-mucin were observed and tentatively attributed to differences in binding kinetics. The zeta potential of dodecylated chitosan-coated liposomes (DC-Lip) showed positive values in both liposomal formulations, i.e., negatively charged and neutral-charge liposomes. These results indicated that DC could be considered a more suitable polymer for coating neutral-charge liposomes than CS because the hydrophobic side chain of DC inserts itself into the lipid bilayer of liposomes. Moreover, CS seemed to be less effective in the coating of a neutral-charge liposome because of the low positive values of its zeta potential. CS provided solely electrostatic forces when used for coating liposomes while DC provided electrostatic and hydrophobic forces due to the long alkyl chain in its backbone. Confocal Laser Scanning Microscopy (CLSM) images indicated that both chitosan-coated liposomes (CS-Lip) and DC-Lip could adhere to and penetrate through the small intestine of rats after oral administration. The pharmacological results showed that DC-Lip had a greater effect in decreasing blood calcium concentration during the first 12 h compared with CS-Lip. Therefore, it can be concluded that dodecylated chitosan can be useful in designing oral liposomal drug delivery systems.     

Effectiveness of submicron-sized, chitosan-coated liposomes in oral administration of peptide drugs

The mucoadhesive behavior of chitosan-coated liposomes in the intestinal tract of the rat was examined to elucidate their particle size effects on the absorption of an entrapped drug, calcitonin. The intestine was removed from rats after oral administration of liposomes containing a fluorescent dye, and its various parts were observed with confocal laser scanning microscopy. Penetration of submicron-sized liposomes (ssLip) or chitosan-coated ssLip (ssCS-Lip) into the mucosa was observed, while such behavior was not observed for the multilamellar liposomes, even when coated with chitosan (CS-Lip). The retentive property of ssCS-Lip was confirmed by measuring the amount of dye in each part of the intestine. The pharmacologic effects of calcitonin-loaded liposomes of different particle size were measured after oral administration in rats. The pharmacologic effect of oral administration of ssLip coated with chitosan was detected up to 120 h after administration. The extensive pharmacologic effect of ssCS-Lip was attributed to their prolonged retention in the intestinal mucosa, partly owing to their penetrative property into the intestinal mucosa. The chitosan-coated ssLip, with their higher retentive property in the intestinal tract, are much more effective than ssLip and CS-Lip in improving the enteral absorption of peptide drugs.     

Low molecular weight chitosan-coated liposomes for ocular drug delivery: in vitro and in vivo studies

In this study, low molecular weight chitosan coated liposomes (LCHL) were designed and prepared for ocular drug delivery, the coating mechanism was studied, and in vitro and in vivo characterization was conducted. The effects of molecular weight and concentration of low molecular weight chitosan on the liposomal coating were studied. The numeric relations between coating variables and coating efficiency were established using a mathematical model. Morphology of LCHL was examined by transmission electron microscopy (TEM). Cytotoxicity and cell internalization of FITC-BSA labeled LCHL in a rabbit conjunctival epithelium (RCE) cell line were studied. Cyclosporin A (CsA) was encapsulated as a model drug, and in vitro drug release and in vivo drug absorption were investigated. LCHL demonstrated low toxicity to RCE cells. In vitro drug release measurement showed that LCHL had a delayed release profile compared with non-coated liposomes. In vivo study in rabbits showed that the concentrations of CsA in cornea, conjunctiva, and sclera were remarkably increased by LCHL. In conclusion, LCHL might be a potential ocular drug carrier with characteristics such as prolonged drug retention, enhanced drug permeation, and biocompatibility.     

Chitosan‐coated antifungal formulations for nebulisation

Objectives The aim of this study was to produce and characterise amphotericin B (AmB) containing chitosan‐coated liposomes, and to determine their delivery from an air‐jet nebuliser. Methods Soya phosphatidylcholine : AmB (100 : 1) multilamellar vesicles were generated by dispersing ethanol‐based proliposomes with 0.9% sodium chloride or different concentrations of chitosan chloride. These liposomes were compared with vesicles produced by the film hydration method and micelles. AmB loading, particle size, zeta potential and antifungal activity were determined for formulations, which were delivered into a two‐stage impinger using a jet nebuliser. Key findings AmB incorporation was highest for liposomes produced from proliposomes and was greatest (approximately 80% loading) in chitosan‐coated formulations. Following nebulisation, approximately 60% of the AmB was deposited in the lower stage of the two‐stage impinger for liposomal formulations, for which the mean liposome size was reduced. Although AmB loading in deoxycholate micellar formulations was high (99%), a smaller dose of AmB was delivered to the lower stage of the two‐stage impinger compared to chitosan‐coated liposomes generated from proliposomes. Chitosan‐coated and uncoated liposomes loaded with AmB had antifungal activities against Candida albicans and C. tropicalis similar to AmB deoxycholate micelles, with a minimum inhibitory concentration of 0.5 µg/ml. Conclusions This study has demonstrated that chitosan‐coated liposomes, prepared by an ethanol‐based proliposome method, are a promising carrier system for the delivery of AmB using an air‐jet nebuliser, having a high drug‐loading that is likely to be effectively delivered to the peripheral airways for the treatment of pulmonary fungal infections.     

Evaluation of Mucoadhesive PLGA Microparticles for Nasal Immunization

In this study, hepatitis B surface antigen (HBsAg) loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared and coated with chitosan and trimethyl chitosan (TMC) to evaluate the effect of coating material for nasal vaccine delivery. The developed formulations were characterized for size, zeta potential, entrapment efficiency, and mucin adsorption ability. Plain PLGA microparticles demonstrated negative zeta potential. However, coated microparticles showed higher positive zeta potential. Results indicated that TMC microparticles demonstrated substantially higher mucin adsorption when compared to chitosan-coated microparticles and plain PLGA microparticles. The coated and uncoated microparticles showed deposition in nasal-associated lymphoid tissue under fluorescence microscopy. The coated and uncoated microparticles were then administered intranasally to mice. Immune-adjuvant effect was determined on the basis of specific antibody titer observed in serum and secretions using enzyme-linked immunosorbent assay. It was observed that coated particles showed a markedly increased anti-HBsAg titer as compared to plain PLGA microparticles, but the results were more pronounced with the TMC-coated PLGA microparticles.     

Formation of size-controlled nano carrier systems by self-assembly

Nano carrier systems were prepared by forming self-assembled liposomes having a size distribution in the nano range through use of an ultrasonic homogenizer. Phosphatidylcholine and cholesterol were utilized as an amphiphilic compound and a shape stabilizer, respectively. The size of prepared samples was decreased (up to 150 nm) by elevating ratio of lecithin and extending homogenization time (2 ～ 6 min). After secondary coating with alginic acid (0.1, 0.3 and 0.5%, W/V), size was remarkably changed in the range of ±30 nm and zeta-potential was altered (only chitosan coating (molecular weight: 30 000 Da, 0.2%, W/V): 10.3 mV, Alginic acid coating (0.5%, W/V) after the chitosan coating: ?21.8 mV). The low molecular weight chitosan (0.1%, W/V)-coated nano-liposomes had a lower absolute value of zeta-potential than the high molecular weight chitosan (0.1%, W/V)-coated nano-liposomes. The encapsulation efficiency was measured by gas chromatography. The efficiency was decreased slightly by elevating chitosan concentration (0.1 ～ 0.5%, W/V).     

Characterisation of chitosan-coated vesicles encapsulating DNA suitable for gene delivery

Encapsulation of DNA (varying type and molecular weight) in vesicles (dehydration-rehydration vesicles; DRV) prepared from zwitterionic phospholipids using the dehydration-rehydration method was determined to be in the range of 10-90%. Encapsulation was dependent on the amount of DNA added but not its molecular weight. Zeta potential measurements of the DRV suggested that DNA was associated with the vesicles exterior, while small angle neutron scattering (SANS) studies indicated that DNA was trapped in the interlamellar water space between lipid bilayers-as evidenced by a slight decrease in bilayer thickness and an increase in d-spacing. Circular dichroism measurements determined the conformation of the DNA in the DRV was not the usual B-form but rather a structure more reminiscent of the less hydrated, C-form, supporting the suggestion that DNA was present in the interlamellar water space. DRV were successfully coated with chitosan as evidenced by SANS studies and zeta potential measurements. The amount of chitosan coating the DRV [quantified by ultra violet (UV)/Vis spectroscopy] was dependent upon the starting concentration of chitosan and independent of the presence of DNA. Chitosan-coated DRV containing DNA exhibited an improved size stability while 'empty' uncoated vesicles were poorly stable. A coating of chitosan reduced the amount of DNA leaking from the vesicles.     

Preparation and characterization of Mitomycin-C loaded chitosan-coated alginate microspheres for chemoembolization

Mitomycin-C loaded and chitosan-coated alginate microspheres were prepared for use in chemoembolization studies. In this respect, first alginate microspheres were prepared by using a spraying method using an extrusion device with a small orifice and following suspension cross-linking in an oil phase. Chitosan-coating onto the alginate microspheres was achieved by polyionic complex formation between alginate and chitosan. CaCl₂ was used as a cross-linker for alginate microspheres. The obtained chitosan-coated alginate microspheres were spherical shaped and ～100–400?µm average size. The microspheres were evaluated based on their swellability and the swelling ratio was changed between 50–280%. CaCl₂ concentration, stirring rate, chitosan molecular weight, chitosan concentration and time for coating with chitosan were selected as the effective parameters on microsphere size and swelling ratio. Equilibrium swellings were achieved in ～30?min. On the other hand, chitosan molecular weight, chitosan concentration and time for coating with chitosan were found as the most effective parameters on both drug loading ratio and release studies. Maximum drug loading ratio of 65% was achieved with high molecular weight (HMW) chitosan, highest chitosan concentration (i.e. 1.0% v/v) and shortest time for coating with chitosan (i.e. 1?h) values.     

Chitosan-coated liposomes: characterization and interaction with leuprolide

The objective of the present work was to investigate the effect of chitosan concentration and lipid type on the characteristics of chitosan-coated liposomes and their interactions with leuprolide. Liposomes from lipid of high purity and low purity were prepared and coated by chitosan. Physical properties, drug entrapment efficiency, and stability upon dilution were respectively compared. Results showed that the particle size increment of liposomes from low purity lipid was larger than that from high purity lipid, indicating a thicker coating layer. The high zeta potential of particles from low purity lipid was thought to play an important role in the resistance to flocculation. As to particles from high purity lipid, polymer bridging caused flocculation at low polymer concentration while at high concentration, the adsorbed chitosan molecule led to steric stabilization. Drug entrapment efficiency decreased as chitosan was added to liposomes, showing the disturbance of bilayers. Upon dilution, the leakage of leuprolide from low purity liposomes was larger than that from high purity liposomes. In conclusion, low purity lipid possessed more negative charge and formed thicker adsorptive layer by stronger electrostatic attraction with chitosan. The interaction between chitosan and the polar head groups on the surface of phospholipid bilayers may interfere with leuprolide entrapped in liposomes and result in the leakage of leuprolide.     

Preparation and characterization of Mitomycin-C loaded chitosan-coated alginate microspheres for chemoembolization

Mitomycin-C loaded and chitosan-coated alginate microspheres were prepared for use in chemoembolization studies. In this respect, first alginate microspheres were prepared by using a spraying method using an extrusion device with a small orifice and following suspension cross-linking in an oil phase. Chitosan-coating onto the alginate microspheres was achieved by polyionic complex formation between alginate and chitosan. CaCl(2) was used as a cross-linker for alginate microspheres. The obtained chitosan-coated alginate microspheres were spherical shaped and approximately 100-400 microm average size. The microspheres were evaluated based on their swellability and the swelling ratio was changed between 50-280%. CaCl(2) concentration, stirring rate, chitosan molecular weight, chitosan concentration and time for coating with chitosan were selected as the effective parameters on microsphere size and swelling ratio. Equilibrium swellings were achieved in approximately 30 min. On the other hand, chitosan molecular weight, chitosan concentration and time for coating with chitosan were found as the most effective parameters on both drug loading ratio and release studies. Maximum drug loading ratio of 65% was achieved with high molecular weight (HMW) chitosan, highest chitosan concentration (i.e. 1.0% v/v) and shortest time for coating with chitosan (i.e. 1 h) values.     

Preparation of chitosan-coated liposomes as a novel carrier system for the antiviral drug Triazavirin

Abstract

Novel method for the coating of positively charged liposomes with modified chitosan was elaborated. Liposomes were prepared by stepwise extrusion through inorganic membranes (Anotop) of 0.2 and 0.1?μm pore sizes. Chitosan derivatives were synthesized via the Ugi multicomponent reaction. Several series of liposomal compositions were produced and their properties were compared in terms of particle size, polydispersity index (PDI), zeta potential and stability. The effect of various additives was investigated and the optimal composition of the lipid film was determined. The addition of the uncharged fatty esters allowed the diameter of the liposomes obtained by extrusion to be reduced to 145–150?nm with a PDI of 0.13–0.15. The prepared liposomes were loaded with the novel antiviral drug Triazavirin and used to determine the release profile. Triazavirin was included into liposome layer as a salt with biocompatible choline derivatives of limiting fatty acids. The appropriate lipid composition was used for the preparation of a larger quantity of liposomes coated by modified chitosan. It was shown that an appropriate combination of liposomes and polysaccharide layer potentially extended colloidal stability by up to 3 months and exhibited broad functional capabilities for surface modification.     

Bioadhesive properties of poly(anhydride) nanoparticles coated with different molecular weights chitosan

The aim of this study was to develop and characterize the bioadhesive properties of poly(anhydride) nanoparticles coated with two types of low-molecular weight chitosan (CH20 of 20?kDa or CH50 of 50?kDa) or their thiolated conjugates. Nanoparticles were prepared by a solvent displacement method and characterized by measuring the size, zeta potential, morphology and composition. For bioadhesion studies, nanoparticles were fluorescently labelled with rhodamine B isothiocyanate. In all cases, coated nanoparticles showed a slightly higher size and lower negative zeta potential than uncoated nanoparticles. Nanoparticles coated with CH20 showed a higher adhesive capacity than uncoated nanoparticles. On the contrary, when nanoparticles were coated with CH50, the resulting carriers displayed a decreased ability to develop adhesive interactions within the gut. Finally, the coating of nanoparticles with thiolated chitosan improved their adhesive abilities. Poly(anhydride) nanoparticles coated with thiolated chitosan can be considered as promising bioadhesive particulate carriers for oral delivery strategies.