Water-soluble Low Molecular Weight Research Articles

Hyperbranched poly(ether amine) (hPEA) as novel backbone for amphiphilic one-component type-II polymeric photoinitiators

To make photoinitiators (PI) to be polymeric and water-soluble is an effective approach to develop the high efficient photoinitiator systems with low-migration, low-toxic and environment-friend. We developed a series of novel amphiphilic hyperbranched polymeric photoinitiators (hPEA-TXs, and hPEA-BPs) by introducing thioxanthone (TX) or benzophenone (BP) moieties into the periphery of the hyperbranched poly(ether amine) (hPEA) comprised of the hydrophilic poly(ethylene oxide) (PEO) short chain and coinitiator amine moieties in the backbone. Compared with their water-soluble low-molecular weight analogues, the resulting hyperbranched polymeric photoinitiators hPEA101-TX, hPEA211-TX, hPEA101-BP and hPEA211-BP could be dissolved very well not only in many organic systems including acrylate monomers, but also in water with high solubility of 10wt%. The photopolymerization kinetics of water-soluble monomer acrylamide (AM) and three hydrophobic multifunctional acrylate monomers initiated by these hyperbranched photoinitiators were investigated in detail by photo-differential scanning calorimetric (photo-DSC). Both hPEA-TXs and hPEA-BPs can initiate photopolymerization of AM as efficiently as their low-molecular weight analogues MGA-TX and MGA-BP, respectively. The final double bond conversion (DBC) of oil-soluble monomer hexanediol diacrylate (HDDA) photoinitiated by these hyperbranched photoinitiators can reach as high as 99%. Especially for photopolymerization of multifunctional monomers initiated by these hyperbranched polymeric photoinitiators, the final DBC of trimethylolpropane triacrylate (TMPTA) and pentaerythritol tetraacrylate (PETTA) can reach 80% and 60%, respectively, which is much higher than that of low-molecular weight photoinitiators.

Detection of over 100 selenium metabolites in selenized yeast by liquid chromatography electrospray time-of-flight mass spectrometry.

The characterization of the selenometabolome of Selenized(Se)-yeast, that is the fraction of water soluble low-molecular weight Se-metabolites produced in Se-yeast is of paramount interest to expand the knowledge on the composition of this food supplement. In this work, we have applied liquid chromatography electrospray time-of-flight mass spectrometry (LC-TOFMS) to search for Se-species from the low molecular weight range fraction of the selenized yeast used for food supplements. Prior to LC-TOFMS, sample treatment consisted of ultrasound assisted water extraction followed by size exclusion fractionation assisted with off-line inductively coupled plasma mass spectrometry detection of isotope 82Se. The fraction corresponding to low-molecular weight species was subjected to LC-TOFMS using electrospray ionization in the positive ion mode. The detection of the suspected selenized species has been based on the information obtained from accurate mass measurements of both the protonated molecules and fragments from in-source CID fragmentation; along with the characteristic isotope pattern exhibited by the presence of Se. The approach enables the detection of 103 selenized species, most of them not previously reported, in the range from ca. 300-650Da. Besides the detection of selenium species, related sulphur derivate metabolites were detected based on the accurate mass shift due to the substitution of sulphur and selenium.

Secondary Organic Aerosol Formation over Coastal Ocean: Inferences from Atmospheric Water-Soluble Low Molecular Weight Organic Compounds.

A lack of consensus on the distributions and formation pathways of secondary organic aerosols (SOA) over oceanic regions downwind of pollution sources limits our ability to assess their climate impact globally. As a case study, we report here on water-soluble SOA components such as dicarboxylic acids, oxocarboxylic acids, and α-dicarbonyls in the continental outflows from the Indo-Gangetic Plain (IGP) and Southeast Asia (SEA) to the Bay of Bengal. Oxalic acid (C2) is the dominant species followed by succinic (C4) and glyoxylic acids (ωC2) in the outflow. Nonsea-salt SO42- also dominates (∼70%) total water-soluble inorganic constituents and correlates well with aerosol liquid water content (LWC) and C2, indicating their production through aqueous phase photochemical reactions. Furthermore, mass ratios of dicarboxylic acids (C2/C4, C2/ωC2), and their relative abundances in water-soluble organic carbon and total organic carbon are quite similar between the two continental (IGP and SEA) outflows, indicating the formation of SOA through aqueous phase photochemical reactions in LWC-enriched aerosols, largely controlled by anthropogenic SO42-.

Uremia Retention Molecules and Clinical Outcomes.

Chronic kidney disease is characterized by the accumulation of organic compounds in the bloodstream that may exert a variety of toxic effects in the body. These compounds, collectively known as uremic toxins, may be classified according to their physicochemical properties as free water-soluble low molecular weight molecules, middle molecules or protein-bound uremic toxins. Most of these retention molecules, due to either their size and/or binding to protein, constitute a complex therapeutic challenge to the nephrologist, particularly in end-stage renal disease, because of their limited removal by conventional dialysis therapies. Therefore, we review in this article the current clinical evidences that have supported the important role of uremic toxins in uremia by contributing to the adverse outcomes related to chronic kidney disease, such as increased mortality and cardiovascular events, as well as renal impairment progression that cannot be solely explained by traditional risk factors. These observations have ultimately contributed to testing new therapeutic targets, such as the gut, and the development of modern dialysis strategies to manage chronic kidney disease patients.

Characterization of a Chitosanase from Jelly Fig (Ficus awkeotsang Makino) Latex and Its Application in the Production of Water-Soluble Low Molecular Weight Chitosans.

A chitosanase was purified from jelly fig latex by ammonium sulfate fractionation (50–80% saturation) and three successive column chromatography steps. The purified enzyme was almost homogeneous, as determined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and gel activity staining. The molecular mass of the enzyme was 20.5 kDa. The isoelectric point (pI) was <3.5, as estimated by isoelectric focusing electrophoresis on PhastGel IEF 3-9. Using chitosan as the substrate, the optimal pH for the enzyme reaction was 4.5; the kinetic parameters Km and Vmax were 0.089 mg mL-1 and 0.69 μmol min-1 mg-1, respectively. The enzyme showed activity toward chitosan polymers which exhibited various degrees of deacetylation (21–94%). The enzyme hydrolyzed 70–84% deacetylated chitosan polymers most effectively. Substrate specificity analysis indicated that the enzyme catalyzed the hydrolysis of chitin and chitosan polymers and their derivatives. The products of the hydrolysis of chitosan polymer derivatives, ethylene glycol (EG) chitosan, carboxymethyl (CM) chitosan and aminoethyl (AE) chitosan, were low molecular weight chitosans (LMWCs); these products were referred to as EG-LMWC, CM-LMWC and AE-LMWC, respectively. The average molecular weights of EG-LMWC, CM-LMWC and AE-LMWC were 11.2, 11.2 and 8.89 kDa, respectively. All of the LMWC products exhibited free radical scavenging activities toward ABTS•+, superoxide and peroxyl radicals.

Chitin Nanofiber Elucidates the Elicitor Activity of Polymeric Chitin in Plants

Chitin, an N-acetyl-D-glucosamine polymer, is a component of fungal cell walls and a microbe/pathogen-associated molecular pattern that elicits plant defense responses. As polymeric chitin is difficult to handle due to its insolubility in water, many studies on chitin-induced immune responses have used water-soluble low-molecular weight chitin instead. Thus, it is unclear if polymeric chitin can induce resistance. Here, we examined the elicitor activity of chitin nanofiber (CNF) of submicron thickness prepared from polymeric chitin. CNF showed a high dispersing ability in water and induced both reactive oxygen species (ROS) production and chitin-induced defense-related gene expression in Arabidopsis thaliana seedlings. The Arabidopsis chitin elicitor receptor kinase 1 (Atcerk1) mutant, which is impaired in chitin perception, also failed to respond to CNF. CNF exposure triggered ROS generation in suspension-cultured cells from Oryza sativa. Furthermore, pre-treatment of Arabidopsis leaves with CNF effectively reduced pathogen infection by both the fungus Alternaria brassicicola and the bacterium Pseudomonas syringae pv. tomato DC3000. These results demonstrate that CNF has elicitor activity and will help define the role of polymeric chitin in plant immune responses.

Development of nanoparticles for clinical use.

During recent years, there has been much interest in using nanoparticles (NPs) for delivery of therapeutic drugs or contrast agents. Many interesting in vitro and animal studies have been reported [1–3], and some NP-based products are already in clinical use. Iron-oxide containing NPs have been used as iron supplement or contrast agents in MRI for more than 20 years [4,5]. Albumin and liposomal-based products containing anticancer drugs have also been available for several years, and new NP-based products are in clinical trials [2,6]. The discrepancy between the large number of papers published about NPs and other drug candidates versus the few new drugs entering the market is heavily debated, and important discussions regarding what is needed to bring new products to the market have been published [6–9]. No doubt, there are many challenges to overcome before NPs may become common tools in clinical practice.

Investigation of Low-molecular Weight Phenol Formaldehyde Distribution in Tracheid Cell Walls of Chinese Fir Wood

Treatment with water-soluble low-molecular weight phenol-formaldehyde resin is an effective method to improve wood properties. In this paper, plantation wood of Chinese fir was modified with low-molecular weight phenol-formaldehyde resin. The absorbance by tracheid cell walls of phenol-formaldehyde resin in treated and untreated reference samples were measured with an ultraviolet micro-spectrophotometer. The UV absorbance values of earlywood tracheids and middle lamella in treated wood were significantly increased, with an average increase of 49% and 23%, respectively. Moreover, after treatment with low-molecular weight phenol-formaldehyde resin, the UV absorbance of the earlywood tracheid cell walls of Chinese fir increased to more than 47%, regardless of whether or not the cell lumens were filled with resin. After treatment with low-molecular weight phenol-formaldehyde resin, the UV absorbance of earlywood tracheid cell walls at different locations did not vary greatly. This study provides direct support for the improvement of the physical and mechanical properties of resin-modified Chinese fir in terms of penetration of the resin into the cell walls.

Mechanistic Studies on the Degradation and Protein Release Characteristics of Poly(lactic-co-glycolic-co-hydroxymethylglycolic acid) Nanospheres

The purpose of this study was to gain mechanistic insights into the effect of different formulation parameters on the degradation and release behavior of protein-loaded nanoparticulate carrier systems based on an aliphatic polyester with pendant hydroxyl groups, poly(lactic-co-glycolic-hydroxymethyl glycolic acid) (pLGHMGA). Bovine serum albumin (BSA) was used as a model protein. BSA-loaded pLGHMGA nanospheres of 400-700 nm were prepared using a solvent evaporation method using pLGHMGA of different molecular weights and different compositions. Also, the concentration of pLGHMGA in the organic phase was varied. The nanospheres showed a continuous mass loss accompanied by continuous decrease in number average molecular weight, which indicates that the degradation of the nanospheres is by bulk degradation with a rapid release of water-soluble low molecular weight fragments. On the basis of NMR analysis, it is concluded that intramolecular transesterification precedes extensive hydrolysis of the polymer and degradation of the nanospheres. BSA-loaded freeze-dried nanospheres showed a significant burst release of 40-50% of the BSA loading. In contrast, nonfreeze-dried samples showed a small burst of around 10-20%, indicating that freeze-drying induced pore formation. Nonlyophilized nanospheres prepared from pLGHMGA with 64/18/18 lactic/glycolic/hydroxymethylglycolic acid (L/G/HMG) ratio showed a relatively fast release of BSA for the next 30 days. Nanospheres prepared from a more hydrophobic pLGHMGA (74/13/13, L/G/HMG) showed a two-phase release. Circular dichroism analysis showed that the secondary structure of the released protein was preserved. This study shows a correlation between release behavior and particle erosion rate, which can be modulated by the copolymer composition.

Promising interaction between nanoencapsulated lutein with low molecular weight chitosan: Characterization and bioavailability of lutein in vitro and in vivo

This study aims to develop water-soluble low molecular weight chitosan (LMWC) nanoencapsules with lutein to improve its bioavailability. Lutein-LMWC nanoencapsules were prepared, characterized and bioavailability was studied in vitro and in vivo with lutein in mixed micelles (control). The particle size ranged between 80–600nm, which was confirmed by Atomic Force Microscope. The interaction between LMWC and lutein in nanocencapsules by 1H and 13C NMR showed the essentiality of water molecules to hold the lutein between LMWC chains of nanoparticle with a reversible weak bond. Bioavailability of lutein (200μM) in vitro showed that lutein-LMWC nanoencapsules was significantly higher (27.7%) than control. Postprandial lutein level in the plasma (54.5%), liver (53.9%) and eyes (62.8%) of mice fed on nanoencapsulated lutein were higher than the control. LMWC may serve as novel carrier for enhancing the lutein bioavailability and can be suggested as the better dietary compound in food and pharmaceutical applications.

Antitumor and immunomodulatory activity of a water-soluble low molecular weight polysaccharide from Schisandra chinensis (Turcz.) Baill

A water-soluble low molecular weight polysaccharide (SCPP11) was extracted and purified using DEAE-cellulose and Sephadex G-100 column from Schisandra chinensis (Turcz.) Baill. Its in vivo and in vitro antitumor and immunomodulatory activity were investigated. The results showed that SCPP11 with a molecular weight of 3.4×10(3)Da exhibited indirect cyctotoxic activity against tumor cells in vitro, but could significantly inhibit the growth of Heps cells in vivo at dose of 50mg/kg, and its inhibition rate is higher than that in the positive group. Moreover, SCPP11 could ameliorate the hematological and biochemical parameters to almost normal and no significant changes in organ weight, and could increase the body weight. In addition, SCPP11 (at 50mg/kg) could also increased in thymus indexes as well as IL-2 and TNF-α levels in serum in vivo and significantly enhance the phagocytosis activity and the productions of NO of RAW264.7 in vitro. The results indicated that antitumor properties of SCPP11 might be achieved by improving immune response. It could be explored as a potential adjuvant against cancer used in the health food and pharmaceutical therapy.

Quantitative Fate of Chlorogenic Acid during Enzymatic Browning of Potato Juice

The quantitative fate of chlorogenic acid (ChA) during enzymatic browning of potato juice was investigated. Potato juice was prepared in water without the use of any antibrowning agent (OX treatment). As a control, a potato juice was prepared in the presence of NaHSO(3) (S control). To study the composition of phenolic compounds in potato in their native states, also a potato extract was made with 50% (v/v) methanol containing 0.5% (v/v) acetic acid (MeOH control). Water-soluble low molecular weight fractions (LMWFs) and high molecular weight fractions (HMWFs) from S and OX extracts were obtained by ultrafiltration and dialysis, respectively. Pellets obtained after the OX treatment and the S and MeOH controls were also analyzed for ChA content. Whereas in the S-LMWF all ChA was converted to sulfonic acid adducts, no free ChA was found in the OX-LMWF, indicating its high reactivity upon enzymatic browning. Analysis of protein in the HMWFs showed a higher content of "reacted" ChA in OX (49.8 ± 7.1 mg ChA/100 g potato DW) than in S (14.4 ± 1.5 mg ChA/100 g potato DW), as evidenced by quinic acid release upon alkaline hydrolysis. The presence of quinic acid in S-HMWF was unexpected, but a mass balance incorporating the ChA content of LMWF, HMWF, and pellet for the three extractions suggested that ChA might have been attached to polymeric material, soluble in the aqueous environment of S but not in that of MeOH. Size exclusion chromatography, combined with proteolysis, revealed that ChA reacted with patatin and protease inhibitors to produce brown soluble complexes.

Study of polypropylene surface modification by air dielectric barrier discharge operated at two different frequencies

In this work, air dielectric barrier discharge (DBD) operating at the line frequency (60Hz) or at frequency of 17kHz was used to improve the wetting properties of polypropylene (PP). The changes in the surface hydrophilicity were investigated by contact angle measurements. The plasma-induced chemical modifications of PP surface were studied by X-ray photoelectron spectroscopy (XPS) and Fourier-transformed infrared spectroscopy (FTIR). The polymer surface morphology and roughness before and after the DBD treatment were analyzed by atomic force microscopy (AFM). To compare the plasma treatment effect at different frequencies the variation of the contact angle is presented as a function of the deposited energy density. The results show that both DBD treatments leaded to formation of water-soluble low molecular weight oxidized material (LMWOM), which agglomerated into small mounts on the surface producing a complex globular structure. However, the 60Hz DBD process produced higher amount of LMWOM on the PP surface comparing to the 17kHz plasma treatment with the same energy dose. The hydrophilic LMWOM is weakly bounded to the surface and can be easily removed by polar solvents. After washing the DBD-treated samples in de-ionized water their surface roughness and oxygen content were reduced and the PP partially recovered its original wetting characteristics. This suggested that oxidation also occurred at deeper and more permanent levels of the PP samples. Comparing both DBD processes the 17kHz treatment was found to be more efficient in introducing oxygen moieties on the surface and also in improving the PP wetting properties.

Modifications of the 1H NMR metabolite profile of processed mullet (Mugil cephalus) roes under different storage conditions

(1)H NMR spectroscopy was employed to study the modifications over time of the water-soluble low molecular weight metabolites extracted from samples of salted and dried mullet (Mugil cephalus) roes (mullet bottarga) stored at different conditions. Samples of grated mullet bottarga were stored for 7 months at -20 °C, at 3 °C, and at room temperature in the presence and in the absence of light and then timely extracted and analyzed by NMR. Principal component multivariate data analysis applied to the spectral data indicated that samples stored at -20 °C maintained similar features over time whereas, along PC1, samples stored at room temperature in the presence and in the absence of light showed, over time, marked metabolite modifications. The comparative analysis of the integrated areas of the selected regions of the (1)H NMR spectra indicated that the major compositional changes due to storage conditions were (i) the increase of the derivatives of the breakdown of phosphatidylcholine (choline, phosphorylcholine, and glycerol), (ii) the breakdown of nucleosides, (iii) the decrease of methionine, tryptophan, and tyrosine, and (iv) the cyclization of creatine. These changes were observed at different storage conditions, with more pronounced trends in the samples stored at room temperature. The role of metabolites in food aging is discussed.

Inhibition of the Peroxidation of Liposomal Lipids by Uric Acid Requires Tocopherol

Urate is the major water-soluble low molecular weight antioxidants in serum, contributing about 50% to the antioxidative potential of the serum. Unexpectedly, both urate, as well as the other major antioxidant ascorbate, promote the copper-induced peroxidation of liposomal PUFA. In a previous study it has been shown that ascorbate inhibits copper-induced oxidation of liposomal lipids when the liposomes contain Tocopherol, whereas urate does not. In an attempt to explain these findings we studied the temporal order of events, by monitoring continuously and simultaneously the time-course of formation of oxidation products and the consumption of the various components of the system. The resultant kinetic profiles show that: 1. Both water-soluble antioxidants slightly inhibit the oxidation of tocopherol; 2. Ascorbate becomes oxidized very rapidly (much faster than tocopherol), whereas urate and tocopherol become oxidized simultaneously. 3. In the presence of tocopherol, both urate and ascorbate inhibit copper-induced peroxidation of PUFA. 4. AAPH-induced peroxidation of liposomal PUFA is inhibited by both urate and ascorbate, independent of the presence of tocopherol. Our interpretation of these results contribute to the understanding of the complex, interdependent dependence of the susceptibility of aggregated (unlike soluble) lipids on all the water-soluble antioxidants. This is particularly important for evaluation of the oxidizability of serum lipids when the serum contains excess urate, as in the case of insulin-resistant and obese subjects.

Amyloid β-Protein Dimers Rapidly Form Stable Synaptotoxic Protofibrils

Nonfibrillar, water-soluble low-molecular weight assemblies of the amyloid β-protein (Aβ) are believed to play an important role in Alzheimer's disease (AD). Aqueous extracts of human brain contain Aβ assemblies that migrate on SDS-polyacrylamide gels and elute from size exclusion as dimers (∼8 kDa) and can block long-term potentiation and impair memory consolidation in the rat. Such species are detected specifically and sensitively in extracts of Alzheimer brain suggesting that SDS-stable dimers may be the basic building blocks of AD-associated synaptotoxic assemblies. Consequently, understanding the structure and properties of Aβ dimers is of great interest. In the absence of sufficient brain-derived dimer to facilitate biophysical analysis, we generated synthetic dimers designed to mimic the natural species. For this, Aβ(1-40) containing cysteine in place of serine 26 was used to produce disulphide cross-linked dimer, (AβS26C)2. Such dimers had no detectable secondary structure, produced an analytical ultracentrifugation profile consistent for an ∼8.6 kDa protein, and had no effect on hippocampal long-term potentiation (LTP). However, (AβS26C)2 aggregated more rapidly than either AβS26C or wild-type monomers and formed parastable β-sheet rich, thioflavin T-positive, protofibril-like assemblies. Whereas wild-type Aβ aggregated to form typical amyloid fibrils, the protofibril-like structures formed by (AβS26C)2 persisted for prolonged periods and potently inhibited LTP in mouse hippocampus. These data support the idea that Aβ dimers may stabilize the formation of fibril intermediates by a process distinct from that available to Aβ monomer and that higher molecular weight prefibrillar assemblies are the proximate mediators of Aβ toxicity.

Potential role of N-Succinyl-Chitosan in immune reconstitution after umbilical cord blood transplantation in mice

How to shorten the immune convalescence required after transplantation in recipients is still an austere medicinal problem. Speed-up recovery means less infection opportunity and high survival. In this study, an immune-deficient mouse model was developed by lethally irradiation to evaluate the immune reconstitution effect of N-Succinyl-Chitosan (NSC), a water soluble low molecular weight chitosan derivative, after umbilical cord blood stem cells transplantation, including hematopoiesis parameters detection, T-cell phenotype analysis and pathological comparison; effects of NSC on proliferation of umbilical cord blood stem cell has also been evaluated in vitro. By comparison and analysis, we found the combination of NSC and hematopoietic growth factors could dramatically shorten the time required for the recovery of hematopoiesis, T-cell phenotype and injured spleen after transplantation, suggesting that NSC may hasten the immune recovery and therefore may shorten the time of exposure to life-threatening opportunistic infections in transplant recipients. Moreover, we demonstrated that NSC was effective on the proliferation and clone of umbilical cord stem cell in vitro, suggesting NSC could speed up the immune reconstitution in umbilical cord blood transplantation by enlarge the number of umbilical cord blood stem cell.

A Novel Polypeptide Derived From Human Lactoferrin in Sodium Hyaluronate Prevents Postsurgical Adhesion Formation in the Rat

The objective of the study was to evaluate whether a peptide derived from human lactoferrin, PXL01 could act safely to reduce the formation of peritoneal adhesions in the rat model and to map the molecular mechanisms of its action. Adhesion formation is a significant problem within every surgical discipline causing suffering for the patients and major cost for the society. For many decades, attempts have been made to reduce postsurgical adhesions by reducing surgical trauma. It is now believed that major improvements in adhesion prevention will only be reached by developing dedicated antiscarring products, which are administrated in connection to the surgical intervention. Anti-inflammatory as well as fibrinolytic activities of PXL01 were studied in relevant human cell lines. Using the sidewall defect-cecum abrasion model in the rat, the adhesion prevention properties of PXL01 formulated in sodium hyaluronate were evaluated. Large bowel anastomosis healing model in the rat was applied to study if PXL01 would have any negative effects on intestine healing. PXL01 exhibits an inhibitory effect on the most important hallmarks of scar formation by reducing infections, prohibiting inflammation, and promoting fibrinolysis. PXL01 formulated in sodium hyaluronate markedly reduced formation of peritoneal adhesions in rat without any adverse effects on wound healing. A new class of synthetically derived water soluble low molecular weight peptide compound, PXL01 showed marked reduction of peritoneal adhesion formation in an animal model without any negative effects on healing. On the basis of these data, a comprehensive adhesion prevention regimen in clinical situation is expected.

Chitosan and Its Use in Design of Insulin Delivery System

The global burden of diabetes is estimated to escalate from about 171 million in 2000 to 366 million people in 2030. The routine of diabetes treatment by injection of insulin incurs pain and has been one major factor negating the quality of life of diabetic patients. The possibility of administering insulin via alternative routes such as oral and nasal pathways has been investigated over the years, but with insulin experiencing risks of enzymatic degradation and poor transmucosal absorption. This leads to the rising needs to develop new formulation strategies emphasizing on the assembly of insulin and excipients into a physical structure to maintain the stability and increase the bioavailability of insulin. Chitosan and its derivatives or salts have been widely investigated as functional excipients of delivering insulin via oral, nasal and transdermal routes. The overview of various recent patented strategies on non-injection insulin delivery denotes the significance of chitosan for its mucoadhesive and able to protect the insulin from enzymatic degradation, prolong the retention time of insulin, as well as, open the inter-epithelial tight junction to facilitate systemic insulin transport. The chitosan can be employed to strengthen the physicochemical stability of insulin and multi-particulate matrix. The introduction of chitosan coat or co-formulation of chitosan with cationic gelatin or electrolytes which provide solidified or partially crosslinked structures retain and/or enhance the positive charges of dosage form necessary to induce mucoadhesiveness. The chitosan is modifiable chemically to produce water-soluble low molecular weight polymer which renders insulin able to be processed under mild conditions, and sulphated chitosan which markedly opens the paracellular channels for insulin transport. Combination of chitosan and fatty acid as hydrophobic nanoparticles promotes the insulin absorption via lymphoid tissue. Attainment of optimized formulations with higher levels of pharmacological bioavailability is deemed possible in future through targeted delivery of insulin using chitosan with specific adhesiveness to the intended absorption mucosa.

Mucoadjuvant properties of lipo- and glycoconjugated derivatives of oligochitosans

Chitosan, (1-4)-2-amino-2-deoxy-beta- d-glucan, is a deacetylated form of chitin, an abundant biodegradable, positively charged natural polysaccharide. Chitosan is used for antigen delivery through mucosal barrier due to its ability to disrupt tight junctions. Here we produced new water-soluble low-molecular weight chitosan (LMW-Chi) lipid derivatives and compared their ability to stimulate humoral response with the effect of unmodified LMW-Chi or its oligosaccharide derivatives. LMW-Chi effectively penetrated into macrophage-like, lymphoid and epithelial cells. It also stimulated in mice IgG production to model proteins delivered either by subcutaneous or intranasal routes. Adjuvant effect of chitosan derivatives was comparable to or lower than that of unmodified LMW-Chi. Thus, it is possible that adjuvant effect is induced by unmodified glucosamine units of chitosan.