Chitosan and Anionic Solubility Enhancer Sulfobutylether-ß-Cyclodextrin-Based Nanoparticles as Dexamethasone Ophthalmic Delivery System for Anti-Inflammatory Therapy.

Cataract surgery interventions are constantly increasing, particularly among adult and elderly patients. This type of surgery can lead to inflammatory states of the ocular anterior segment (AS), usually healed via postoperative treatment with dexamethasone (DEX)-containing eye drops. The application of eye drops is challenging due to the high number of daily administrations. In this study, mucoadhesive nanoparticles (NPs) were formulated to improve the residence time of DEX on the corneal mucosa, enhancing the drug's solubility and bioavailability. The NPs were generated using an ionotropic gelation technique, exploiting the interaction between the cationic group of chitosan (CS) and the anionic group of sulfobutylether-ß-cyclodextrin (SBE-ß-CD). The formation of the inclusion complex and its stoichiometry were studied through phase solubility studies, Job's plot method, and Bi-directional transport studies on MDCKII-MDR1. The obtained NPs showed good chemical and physical characteristics suitable for drug loading and subsequent testing on animal mucosa. The DEX-loaded CS/SBE-ß-CD NPs exhibited a prolonged residence time on animal mucosa and demonstrated enhanced drug permeability through the corneal membrane, showing a sustained release profile. The developed NPs posed no irritation or toxicity concerns upon local administration, making them an optimal and innovative drug delivery system for inflammatory AS diseases treatment.

Synthesis of a Rivastigmine and Insulin Combinational Mucoadhesive Nanoparticle for Intranasal Delivery.

Efficient drug delivery remains a critical challenge for treating neurodegenerative diseases, such as Alzheimer's disease (AD). Using innovative nanomaterials, delivering current medications like acetylcholinesterase inhibitors to the brain through the intranasal route is a promising strategy for managing AD. Here, we developed a unique combinational drug delivery system based on N,N,N-trimethyl chitosan nanoparticles (NPs). These NPs encapsulate rivastigmine, the most potent acetylcholinesterase inhibitor, along with insulin, a complementary therapeutic agent. The spherical NPs exhibited a zeta potential of 17.6 mV, a size of 187.00 nm, and a polydispersity index (PDI) of 0.29. Our findings demonstrate significantly improved drug transport efficiency through sheep nasal mucosa using the NPs compared to drug solutions. The NPs exhibited transport efficiencies of 73.3% for rivastigmine and 96.9% for insulin, surpassing the efficiencies of the drug solutions, which showed transport efficiencies of 52% for rivastigmine and 21% for insulin ex vivo. These results highlight the potential of a new drug delivery system as a promising approach for enhancing nasal transport efficiency. These combinational mucoadhesive NPs offer a novel strategy for the simultaneous cerebral delivery of rivastigmine and insulin, which could prove helpful in developing effective treatments of AD and other neurodegenerative conditions.

The Know-how of Polymeric Nanocarrier Based Vaginal Drug Delivery System: Pitfalls, Challenges and Trends.

OBJECTIVE: Gynecological health is a global concern, and thus, the formulator researcher strives to improve the quality of life through innovative feminine pharmaceutical formulations. Vaginal delivery appears to be one of the vital strategies for local and systemic action of the therapeutically active agent. The rich vascular network, mucosal permeability, bypass of hepatic first-pass effect, and low enzymatic activity are the exclusive advantages of the vaginal route. But certain hindrances truncate the vaginal route, such as physiological factors including lower pH, self-cleansing mucus with constant secretion, and varying thickness of mucus layer due to menstrual cycle and microbiota. Significance of Review: This present review envisages the advances in the polymeric nanocarriers in the delivery to the vaginal route. Polymeric (mucoadhesive and PEGylated, etc.) nanocarriers have been recently utilized for drug delivery purposes. The modernized analysis of the updated advancements in the polymeric nanocarrier-based vaginal drug delivery system with the budding development is compiled in the present review. RESULT: The literature search reveals that the novel polymeric nanocarrier design strategies currently being proposed to perk up the delivery of customary drugs through the vaginal route prove effective. CONCLUSION: Polymeric nanocarrier for vaginal delivery has provided better therapeutic efficacy due to higher drug residence, improved permeation, and sustained release of the active therapeutic agent. The polymeric nanocarriers can deliver different proteins, peptides, nuclear materials, hormones, etc., vaginally that are difficult for administration.

Metronidazole loaded chitosan-phytic acid polyelectrolyte complex nanoparticles as mucoadhesive vaginal delivery system for bacterial vaginosis.

Bacterial vaginosis (BV) is a recurring infection that is difficult to treat due to the limited bioavailability of antimicrobials. In this study, Metronidazole (MTZ)-loaded chitosan nanoparticles (MCSNP) were synthesized employing phytic acid (PA) as a crosslinking agent for treating bacterial vaginosis. The prepared MCSNPs were characterized for size, shape, surface charge, compatibility, cytotoxicity, biofilm inhibition, and in-vitro/in-vivo antimicrobial activities. Morphological examination revealed that nanoparticles generated from 0.535 % w/v chitosan and 0.112 % w/v PA were non-spherical, discontinuous, and irregular, with zeta potential ranging from 25.00 ± 0.45 to 39 ± 0.7. The results of DSC and XRD demonstrated no change in the physical state of the drug in the finished formulation. The optimized formulation demonstrates a cumulative drug release of about 98 ± 1.5 % within 8 h. Antimicrobial studies demonstrated that the optimized formulation had enhanced efficacy against acid-adapted BV pathogens, with a MIC value of 0.9 ± 0.1 µg/mL. Compared to the MTZ alone, the in-vivo antibacterial results of in the case of developed nanoparticles showed a four-fold reduction in bacterial count in female Swiss albino mice. Based on the experimental findings, it was concluded that MCSNPs, due to their excellent physiochemical and antibacterial properties, could serve as a potential topical alternative for treating BV.

Synthesis of an insulin-loaded mucoadhesive nanoparticle designed for intranasal administration: focus on new diffusion media.

Intranasal administration is a drug delivery approach to provide a non-invasive pharmacological response in the central nervous system with relatively small peripheral side effects. To improve the residence time of intranasal drug delivery systems in the nasal mucosa, mucoadhesive polymers (e.g., chitosan) can be used. Here, insulin-loaded chitosan nanoparticles were synthesized and their physiochemical properties were evaluated based on requirements of intranasal administration. The nanoparticles were spherical (a hydrodynamic diameter of 165.3 nm, polydispersity index of 0.24, and zeta potential of +21.6 mV) that granted mucoadhesion without any noticeable toxicity to the nasal tissue. We applied a new approach using the Krebs-Henseleit buffer solution along with simulated nasal fluid in a Franz's diffusion cell to study this intranasal drug delivery system. We used the Krebs-Henseleit buffer because of its ability to supply glucose to the cells which serves as a novel ex vivo diffusion medium to maintain the viability of the tissue during the experiment. Based on diffusion rate and histopathological endpoints, the Krebs-Henseleit buffer solution can be a substituent solution to the commonly used simulated nasal fluid for such drug delivery systems.

Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin.

Curcumin (CUR) has a regulatory effect on the gut microbiota (GM), and its significant anti-inflammatory properties make it a research hotspot for inflammatory bowel disease (IBD) treatment. However, the low bioavailability and poor pharmacokinetic properties of CUR limit its practical application. Herein, CD44 and GM dual-targeted nanoparticles (NPs) loaded with CUR (CUR@Chs-PNC NPs) were derived from a quaternized chitosan and surface functionalization with chondroitin sulfate (Chs). The generated CUR@Chs-PNC NPs had an ideal average particle size (238.9 â€‹nm), a uniform size distribution, and a positive surface charge (+41.93 â€‹mV). Strikingly, the CUR@Chs-PNC NPs had a good sustained-release effect in a simulated gastrointestinal environment and exhibited the full drug release when in a simulated colon environment. Moreover, Chs functionalization endowed the NPs with a notable CD44-targeted drug delivery ability and thereby enhanced the CUR content in the plasma of SD rats. The biodistribution of the CUR@Chs-PNC NPs in vivo indicated that the NPs could prolong the intestinal residence time, thereby promoting the interaction between CUR and GM. Most importantly, in a DSS-induced colitis mouse model, the CUR@Chs-PNC NPs decreased the disease activity index, improved the oxidative stress and inflammation condition, promoted the production of short-chain fatty acids (SCFAs), regulated immune cells, and maintained intestinal microbiome homeostasis. This study demonstrates that CUR@Chs-PNC NPs, which exhibit excellent biocompatibility and biodegradability, on-demand drug release property, and CD44 and GM dual-targeted capacities, have the potential for further application in the treatment of colitis.

Mucoadhesive Formulation Designs for Oral Controlled Drug Release at the Colon.

Mucoadhesive formulations have been demonstrated to result in efficient drug delivery systems with advantages over existing systems such as increased local retention and sustained drug release via adhesiveness to mucosal tissues. The controlled release of colon-targeted, orally administered drugs has recently attracted a number of studies investigating mucoadhesive systems. Consequently, substantial designs, from mucoadhesive cores to shells of particles, have been studied with promising applications. This review will provide an overview of specific strategies for developing mucoadhesive systems for colon-targeted oral delivery with controlled drug release, including mucoadhesive matrices, cross-linked mucoadhesive microparticles, coatings and mucoadhesive nanoparticles. The understanding of the basic principle of these designs and advanced formulations throughout will lead to the development of products with efficient drug delivery at the colon for therapies for different diseases.

Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-ß-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study.

Peptide oral administration is a hard goal to reach, especially if the brain is the target site. The purpose of the present study was to set up a vehicle apt to promote oral absorption of the neuropeptide dalargin (DAL), allowing it to cross the intestinal mucosal barrier, resist enzymatic degradation, and transport drugs to the brain after crossing the blood-brain barrier. Therefore, a chitosan quaternary ammonium derivative was synthesized and conjugated with methyl-ß-cyclodextrin to prepare DAL-medicated nanoparticles (DAL-NP). DAL-NP particle size was 227.7 nm, zeta potential +8.60 mV, encapsulation efficiency 89%. DAL-NP protected DAL from degradation by chymotrypsin or pancreatin and tripled DAL degradation time compared to non-encapsulated DAL. Use of DAL-NP was safe for either Caco-2 or bEnd.3 cells, with the latter selected as a blood-brain barrier model. DAL-NP could also cross either the Caco-2 or bEnd.3 monolayer by the transepithelial route. The results suggest a potential DAL-NP ability to transport to the brain a DAL dose fraction administered orally, although in vivo experiments will be needed to confirm the present data obtained in vitro.

Cloxacillin nanostructured formulation for the treatment of bovine keratoconjunctivitis.

Infectious bovine keratoconjunctivitis (IBK) is a widespread, contagious ocular disease that affects cattle, especially dairy breeds. The disease is caused by Gram-negative bacteria mainly Moraxella bovis, and its treatment consists of parenteral or topic antibiotic therapy. The topic treatment approach is used more commonly in lactating cows, to avoid milk disposal. However, treatment failures are common, because the antibiotic is removed during lacrimation. This study aimed to evaluate the susceptibility of commercial cloxacillin and evaluate the efficacy of nanostructured cloxacillin in clinical cases of IBK by Moraxella. The minimum inhibitory concentration (MIC) of nanoparticle cloxacillin nanocoated, the nanoparticle without the antibiotic and the commercial cloxacillin were determined in vitro with field samples of Moraxella ovis (5) and Moraxella bovis (5). The efficiency of nanoparticles was tested in three cows naturally infected that were treated with 1.0 mL (with 0.32 mg of nanostructured cloxacillin) for the ocular route. Moraxella bovis was isolated and identified by biochemical and molecular methods before the treatment. The animals were treated every 12 h for six days. The cure was considered by the absence of clinical symptoms and bacteria after treatment. The mucoadhesive nanoparticle-based formulation promoted clinical cure with a low number of doses of antibiotics, probably due to the maintenance of the MIC in the ocular mucosa for longer due to the mucoadhesive characteristics of the nanoparticle. The results indicate that the use of nanocoated cloxacillin is possible to control infectious bovine keratoconjunctivitis.

Impact of Different Mucoadhesive Polymeric Nanoparticles Loaded in Thermosensitive Hydrogels on Transcorneal Administration of 5-Fluorouracil.

In a previous paper a thermosensitive hydrogel formulation based on chitosan or its derivatives (TSOH), containing medicated chitosan nanoparticles (Ch NP) for transcorneal administration of 5-fluorouracil (5-FU) was described. The Ch NP-containing TSOH allowed a time-constant 5-FU concentration in the aqueous for 7 h from instillation. The aim of the present work was to study the impact of the surface characteristics of new NP contained in TSOH on ocular 5-FU bioavailability. The Ch derivatives used to prepare NP were quaternary ammonium-Ch conjugate (QA-Ch), S-protected derivative thereof (QA-Ch-S-pro), and a sulphobutyl chitosan derivative (SB-Ch). All NP types had 300-400 nm size, 16-18% encapsulation efficiency, and retained the entrapped drug for at least 15 h. Drug release from TSOH containing NP based on QA-Ch or QA-Ch-S-pro was virtually equal, whereas with TSOH containing NP based on SB-Ch was significantly slower. Instillation, in rabbit eyes, of NP-containing TSOH based on QA-Ch or SB-Ch led to a plateau in the aqueous concentration vs. time plot in the 1-10 h range with significantly enhanced area under curve (AUC). Negative charges on the NP surface slowed down 5-FU release from TSOH while positive charges increased NP contact with the negatively charged ocular surface. Either results in enhanced ocular bioavailability.

Impact of mucoadhesive polymeric nanoparticulate systems on oral bioavailability of a macromolecular model drug.

Nanoparticles (NP) only different in mucoadhesivity are compared for impact on drug oral bioavailability. Two polymeric NP types based on quaternary ammonium-chitosan (NP QA-Ch) and S-protected thiolated derivative thereof (NP QA-Ch-S-pro), respectively, containing the macromolecular drug model, FD4, were prepared by crosslinking each polymer with reduced MW hyaluronic acid. The structure of basic polymers was determined by H1NMR analysis. NP were similar in size (371 ±â€¯38 vs. 376 ±â€¯82 nm); polydispersity index (0.39 ±â€¯0.08 vs. 0.41 ±â€¯0.10); zeta potential (13.4 ±â€¯0.9 vs. 11.9 ±â€¯1.2 mV); reversible interactions with drug (bound drug, 67 vs. 66%); encapsulation efficiency (23 ±â€¯5 vs. 23 ±â€¯8%); release properties (15% released in 15 h in both cases); and apparent permeation across excised rat intestine (Papp, 8.8 ±â€¯0.8 vs. 10 ±â€¯1 cm/s). Then the differences in NP transport ratio through mucus (TR, 0.75 vs. 0.37) and adhesion to excised rat intestinal mucosa (adsorbed fraction, 23 ±â€¯3 vs. 45 ±â€¯2%) were ascribed to higher mucoadhesivity of NP QA-Ch-S-pro compared to NP QA-Ch. This directly influenced drug oral bioavailability in rats (Tmax, 1 vs. 2 h; AUC, 1.7 ±â€¯0.3 vs. 2.9 ±â€¯0.4 µg/mL min, for NP QA-Ch and NP QA-Ch-S-pro, respectively). Mucoadhesivity increases drug bioavailability by retaining NP at its absorption site and opposing its transit down the GI tract. Data on drug accumulation in rat liver allows the assertion that NP is absorbed by transcytosis across intestinal epithelium and transported from blood into liver by Kuppfer cells.

Nanoparticle mucoadhesive system as a new tool for fish immune system modulation.

Recently, chitosan-based nanoparticles with mucoadhesive properties emerged as a strategy for mucosal drug release. This study aimed to characterize the interaction of mucoadhesive system chitosancoated PLGA nanoparticles (NPMA) with fish external mucus. NP suspensions with fluorescent probe were prepared and characterized by size, polydispersity, zeta potential and pH measures. In post-exposure fish were observed an increase in fluorescence imaging over time and it was significantly influenced by NPMA concentration. We also observed the main predominance the fluorescence in the spleen, followed by liver, gill and other tissues. The use of mucoadhesive nanocarriers becomes an alternative for administration of drugs and immunomodulators in immersion systems since the nanosystem can adhere to the mucosal surface of the fish with little residual effect in the water.

Methyl-ß-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex.

PURPOSE: The present study aimed to compare a novel cyclodextrin-polymer-drug complex in solution with a dispersed supramolecular nanosize system, made of the same complex, for ability to carry dexamethasone (DEX) across excised rat intestine. RESULTS: Methyl-ß-cyclodextrin-quaternary ammonium chitosan conjugate (QA-Ch-MCD) was obtained by covalent grafting through a 10-atom spacer. The conjugate was characterized by 1H-NMR, resulting in 24.4% w/w of MCD content. Phase solubility profile analysis of the QA-Ch-MCD/DEX complex yielded an association constant of 14037 M-1, vs 4428 M-1 for the plain MCD/DEX complex. Nanoparticle (NP) dispersions resulted from ionotropic gelation of the QA-Ch-MCD/DEX complex by sodium tripolyphosphate, leading to 9.9%±1.4% drug loading efficiency. The mean diameter and zeta potential for NP were 299±32 nm (polydispersity index [PI] 0.049) and 11.5±1.1 mV, respectively. Those for QA-Ch-MCD/DEX were 2.7±0.4 nm (PI 0.048) and 6.7±0.6 mV. QA-Ch-MCD/DEX solutions and corresponding NP dispersions were compared in vitro for water-assisted transport through mucus, DEX permeation through excised rat intestine, and ex vivo mucoadhesivity. The complex showed higher mucoadhesion and lower transport rate through mucus; also, it provided faster drug permeation across excised rat intestine. CONCLUSION: Carrier adhesion to mucus surface has played a most important role in favoring transepithelial permeation. Then, within the concerns of the present study, the use of NP seems not to provide any determinant advantage over using the simpler macromolecular complex.

Functional nanocarrier for drug and gene delivery via local administration in mucosal tissues.

Local administration has many advantages for treating diseases. However, the surface mucus layer becomes a major obstacle that easily traps and fast removes local administrated drugs and genes in mucosal tissues. Fortunately, the rapidly developing nanocarriers with special physical and chemical properties may help to refine the treatment of mucosal tissues via delivering drugs and genes to the target tissue, and prolong the drug action time. Therefore, this review focuses on the strategies to apply different nanocarriers for drug-delivery in mucosal tissues, including mucoadhesive and mucus-penetrating types. Delivering drugs and genes to anatomical sites with high mucus turnover becomes more feasible and effective, and maintains sufficient local drug concentration to improve treatment efficacy.

Preparation and performance of pH-responsive nanocarriers for mucus penetration / 国际生物医学工程杂志

Objective To prepare pH-responsive osmotic nanocarriers (pMPPs),observe their distribution in the genital tract mucosa in mice,and evaluate their radiosensitizing effects in tumor cells.Methods Amphiphilic polymers containing pH-sensitive hydrazone bonds were synthesized and pMPPs were prepared by ultrasonic emulsification.At the same time,the hydrophobic polymer polylactic acid-glycolic acid copolymer (PLGA) and the amphiphilic polymer PLGA-polyethylene glycol without hydrazine bond were selected,and the mucoadhesive nanoparticles(MPs) and mucus-penetrating particles (MPPs) were prepared in the same way.Fluorescence microscopy was used to observe the distribution of three kinds of nanocarriers labeled with fluorescent dye Cy5.5 in the genital tract mucosa.The toxicity of nanocarriers to human cervical cancer cell line HeLa was tested by thiazolyl blue assay.The amphiphilic polymer containing pH-sensitive hydrazone bond was combined with oil-soluble gold nanoparticles to form a multi-encapsulated nanocarrier,and its radiotherapy sensitization effect in HeLa cells was evaluated by thiazole blue assay.Results The pMPPs were successfully prepared with relatively uniform particle size and good dispersion.Fluorescence microscopy showed that pMPPs not only had good mucus permeability,but also could improve the endocytosis efficiency of the nanocarriers in reproductive tract mucosa.The results of thiazolyl blue test showed that when the concentration of the carrier reached to 0.80 mg/ml,the survival rate of HeLa cells in the pMPPs group was higher than 90％ which was higher than that in the MPs and the MPPs groups,indicating that pMPPs had good biosafety.The HeLa cell survival rate of the CMNa group (0.80 mg/ml) was higher than that of the multi-package nanocarrier group under different doses of X-ray irradiation (4 Gy:82.90％ vs.61.79％;8 Gy:64.75 ％ vs.42.36％).This result indicated that compared with the CMNa,a commonly used clinical radiotherapy sensitizer,the multi-encapsulated nanocarriers can more effectively enhance the sensitivity of tumor cells to radiation therapy,thereby improving the lethality of radiation therapy on tumor cells.Conclusion This study solved the conflict between mucus permeation and endocytosis design of nanocarriers in mucosal tissue application,and provided new insight for the treatment of mucosal tissue diseases.

About the impact of water movement on the permeation behaviour of nanoparticles in mucus.

The purpose of this study was to establish a method to evaluate the diffusion behaviour of nanoparticles (NP) in mucus taking also the water movement into account. For this purpose, NP based on different chitosan derivatives, either thiolated or not, and marked with fluorescein diacetate were prepared by ionotropic gelation with hyaluronan. NP size and polydispersity were in the respective intervals 363.5±33.3-385.7±36.5nm, and 0.35±0.11-0.39±0.10. An in vitro study of water-assisted NP transport through mucus was realized by filling the barrel of a syringe kept in vertical position, tip down, with mucus. Then a bottom-to-surface PBS flow across the mucus layer was realized by connecting the tip of the syringe to the bottom of a vertical cylindrical vessel by a flexible tubing, filling the vessel with PBS, level with the surface of the mucus layer in the syringe, and dripping PBS into the vessel without causing any phase mixing. Although the mucoadhesive NP interact more strongly with the mucus, yet they are able to overcome this barrier with the aid of the water movement from lumen to epithelium. This new method promises to be more predictive of in vivo NP transport across the mucus than already reported methods, as it takes into account the water movement and regulates its contribution to the physiologic value.

Prolonged Ocular Retention of Mucoadhesive Nanoparticle Eye Drop Formulation Enables Treatment of Eye Diseases Using Significantly Reduced Dosage.

Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance.

Preparation and characterization of mucoadhesive nanoparticles of poly (methyl vinyl ether-co-maleic anhydride) containing glycyrrhizic acid intended for vaginal administration.

Traditional vaginal preparations reside in the vaginal cavity for relatively a short period of time, requiring multiple doses in order to attain the desired therapeutic effect. Therefore, mucoadhesive systems appear to be appropriate to prolong the residence time in the vaginal cavity. In the current study, mucoadhesive nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) intended for vaginal delivery of glycyrrhizic acid (GA) (a drug with well-known antiviral properties) were prepared and characterized. Nanoparticles were generated by a solvent displacement method. Incorporation of GA was performed during nanoprecipitation, followed by adsorption of drug once nanoparticles were formed. The prepared nanoparticles were characterized in terms of size, Z-potential, morphology, drug loading, interaction of GA with PVM/MA (by differential scanning calorimetry) and the in vitro interaction of nanoparticles with pig mucin (at two pH values, 3.6 and 5; with and without GA adsorbed). The preparation method led to nanoparticles of a mean diameter of 198.5 ± 24.3 nm, zeta potential of -44.8 ± 2.8 mV and drug loading of 15.07 ± 0.86 µg/mg polymer. The highest mucin interaction resulted at pH 3.6 for nanoparticles without GA adsorbed. The data obtained suggest the promise of using mucoadhesive nanoparticles of PVM/MA for intravaginal delivery of GA.

Xyloglucan-block-poly(ϵ-caprolactone) copolymer nanoparticles coated with chitosan as biocompatible mucoadhesive drug delivery system.

The development of novel xyloglucan-block-poly(ϵ-caprolactone) (XGO-b-PCL) nanoparticles coated with the mucoadhesive polysaccharide chitosan is described. XGO-b-PCL nanoparticles show monodisperse size distribution (Rh = 50 nm). Curcumin is successfully encapsulated within the PCL core within drug to polymer ratio of 1:5 (w/w). The coating of nanoparticles with chitosan results in an increased particle size and positive surface charge due to the polycation nature of the chitosan. Mucoadhesive properties of chitosan-coated nanoparticles are demonstrated by its exceptional ability to interact with mucin through electrostatic forces. Finally, in vitro studies show that curcumin-loaded nanoparticles exhibit higher cytotoxic effects against B16F10 melanoma cells than L929 fibroblast cells.