Drug-loaded Chitosan Nanoparticles Research Articles

Synthesis, Characterization and Drug Release Study of Novel Guided Tissue Regeneration Membranes Containing Drug Loaded Chitosan Nanoparticles

Periodontitis is an inflammatory disease which can cause the destruction of the supporting tissues of the tooth leading to tooth loss. The guided tissue regeneration is considered as a gold standard for its treatment but the re-infection of surgical site limits its overall success. Objective: To synthesize novel monolayer guided tissue regeneration (GTR) membrane containing drug loaded chitosan nanoparticles and to evaluate the drug release from the synthesized GTR membranes. Methods: The chitosan nanoparticles containing ciprofloxacin were synthesized by the ionotropic gelation method and these synthesized nanoparticles were added into chitosan GTR membrane fabricated by the freeze gelation method. For comparison GTR membrane was prepared as a control by freeze gelation method in which the drug was added directly. The prepared membranes were characterized by the SEM and FTIR. The drug release was measured from the membrane samples in the phosphate buffer saline (PBS) at 1, 3, 5, 7 and 9 days. Results: The GTR membrane containing the ciprofloxacin loaded chitosan nanoparticles showed fast drug release as compared to the membrane in which the ciprofloxacin was added directly. Conclusions: The inclusion of antibiotic loaded chitosan nanoparticles can increase the drug release from GTR membrane.

Anticancer Drug-Loaded Chitosan Nanoparticles for In Vitro Release, Promoting Antibacterial and Anticancer Activities.

Targeted drug delivery to tumor cells may be possible using nanoparticles containing human therapeutic drugs. The present study was carried out to develop cisplatin (CP) and 5-fluorouracil (FA) encapsulated chitosan nanoparticles (CSNPs), crosslinked with sodium tripolyphosphate (TPP) by an ionic gelation method and in vitro release, promoting antibacterial and anticancer activities. The prepared CSNPs, before and after CP and FA encapsulation, have been studied using various characterization techniques such as FTIR, XRD, SEM, and TEM-SAED patterning. The composites were well-dispersed, with an average particle size diameter of about 395.3 ± 14.3 nm, 126.7 ± 2.6 nm, and 82.5 ± 2.3 nm, respectively. In vitro release studies indicated a controlled and sustained release of CP and FA from the CSNPs, with the release amounts of 72.9 ± 3.6% and 94.8 ± 2.9%. The antimicrobial activity of the CSNPs-FA (91.37 ± 4.37% and 89.28 ± 3.19%) showed a significantly better effect against E. coli and S. aureus than that shown by the CSNPs-CP (63.41 ± 3.84% and 57.62 ± 4.28%). The HCT-116 cell lines were selected for in vitro cell cytotoxicity and live/dead assay to evaluate the preliminary anticancer efficacy of the CSNPs-CP and CSNPs-FA towards successfully inhibiting the growth of cancer cells.

Synthesis and characterization of bisacodyl loaded chitosan nanoparticles (BSL@CS NPs), multispectroscopic study of their interaction with bovine serum albumin (BSA)

The novel nanoparticles i.e., bisacodyl (BSL) drug loaded chitosan nanoparticles (BSL@CS NPs) have been synthesized by using the ionotropic gelation method. The obtained nanoparticles were then characterized using different characterization techniques (FTIR, PXRD, SEM and TEM), which showed presence of spherical shaped BSL@CS NPs. Further, the interaction between bovine serum albumin (BSA) and BSL@CS NPs (BSA-BSL@CS NPs system) have been evaluated through multispectroscopic (fluorescence spectroscopy, synchronous fluorescence spectroscopy, UV spectroscopy and CD spectroscopy) techniques. The spectroscopic results indicated presence of static quenching mechanism and induced conformational changes (increase in hydrophobicity) in BSA. The secondary structural content changes (decrease in α-helical content), but preserving of major α-helical content was also suggested from CD spectra of the BSA-BSL@CS NPs system.

Greater efficiency of polyherbal drug encapsulated biosynthesized chitosan nano-biopolymer on diabetes and its complications

Diabetes is a highly complex disease that has an adverse impact on the lives of individuals, and the current medicines used to manage diabetes have obvious side effects. Medicinal plants, on the other hand, may serve as an alternate source of anti-diabetic drugs. A polyherbal combination has a higher and more extensive therapeutic potential than a single herb. Yet, due to deterioration during the absorption process, the usage of this drug still yields inadequate results. Encapsulation of polyherbal drug with chitosan nanoparticles is one of the key ways to solve this problem due to its biocombatibilty, slow and targeted drug delivery characteristics. In the present study, the chitosan was derived from prawn shell and the chitosan nanoparticles had been prepared by ionic-gelation method. The anti-diabetic polyherbal drug (Andrographis paniculata, Andrographis alata, Adhatoda zeylanica, Gymnema sylvestre, Syzygium cumini, and Justicia glabra) was encapsulated with a bio-derived chitosan biopolymer. The drug loading efficiency was about 85 %. The chemical and physical properties of the chitosan and drug-loaded chitosan nanoparticles had been analyzed by FT-IR absorption, XRD, SEM, TEM and EDAX analysis. The antidiabetic efficiency, hepatoprotective activity and antihyperlipedimic activity of the chitosan nanoparticles, polyherbal drug and polyherbal drug encapsulated with chitosan nanoparticles were assessed in a group of rats. The polyherbal drug reduced the serum glucose level from 306.4 mg/dL to 134.47 mg/dL, while the polyherbal drug encapsulated with chitosan nanoparticles reduced to 127.017 mg/dL. This was very close to the serum glucose level of non-diabetic rat (124.65 mg/dL). Further, it considerably increased the insulin level close to that of non-diabetic rat. Thus, the polyherbal drug encapsulated with chitosan nanoparticles showed superior efficiency in antidiabetic and also diabetic complications.

Spray-dried tenofovir alafenamide-chitosan nanoparticles loaded oleogels as a long-acting injectable depot system of anti-HIV drug

The development of suitable drug delivery systems for prolonged action against HIV receives great attention in recent research. Herein, a long-acting injectable (LAI) of Tenofovir alafenamide-chitosan polymeric nanoparticles loaded oleogels developed with sesame oil and ethyl cellulose for prolonged release of the drug is reported for the first time. The research resulted with unique long-acting parenteral formulation for chronic anti-retroviral therapy, based on our experimental in-vitro and ex-vivo studies. The chitosan nanoparticles with 49 % drug content were produced through the spray-drying technique and characterized for their size (106–540 nm) and the other physico-chemical features through SEM, FT-IR, XRD, TGA, and DSC. The ethyl cellulose and sesame oil oleogels were developed through a heat-cool process by incorporating the drug-loaded chitosan nanoparticles. The oleogels exhibited extended release (56 %) of the drug for 16 days, which could be prolonged further to achieve the maximum drug release. Also, the ex-vivo permeation studies of the nanoparticles loaded oleogels demonstrated about 10-fold decrease in the flux and the permeation of the drug due to prolonged release of the drug across dual barriers of chitosan nanoparticles and ethyl cellulose gel matrix. The result provided proof-of-evidence that the developed Tenofovir alafenamide-chitosan polymeric nanoparticles loaded with ethyl cellulose oleogels could be potentially used as the long-acting injectable system for the treatment of patients infected with HIV/AIDS.

Alginate-coated chitosan nanoparticles for pH-dependent release of tamoxifen citrate

Chitosan-based nano-sized particles increase the penetration of the drug through the narrow junction into the bloodstream and target the specific site. The objective of this study was to prepare chitosan nanoparticles to entrap a hydrophobic drug (tamoxifen citrate), followed by the alginate coating of the developed nanoparticles to decrease their degradation in the acidic pH. Drug-loaded chitosan nanoparticles were prepared by the ionic gelation method. Alginate coating was done by dissolving sodium alginate to buffer solution and drug-loaded chitosan nanoparticles drop-wise under mild agitation. The size of alginate coated chitosan nanoparticles, zeta potential, surface morphology, in-vitro drug release, and entrapment efficiency was measured. The optimised formulation of both uncoated (SH3) and coated (SH7) formulation showed the particle size, PDI, and zeta potential with values 221 & 338 nm, 0.161 & 0.230 and 36.5 & −20.7 mV, respectively. The resulted nanoparticle surface was non-porous. The percentage yield of the optimised formulation SH3 was 28% and SH6 was 33%. The entrapment efficiency of the optimised formulation SH3 (uncoated formulation) and SH6 (coated formulation) is 69.5 and 58.51%, respectively. Chitosan nanoparticles were successfully prepared to entrap tamoxifen citrate. The coating of chitosan nanoparticles decreased their degradation in the acidic pH.

Development and Characterization of Anti-alzheimer Drug-loaded Chitosan Nanoparticles for the Enhanced Penetration of Blood Brain Barrier

Nanotechnology facilitated drug delivery has been used to enhance the drug bioavailability, efficacy, reduce toxicity and improve patient compliance aiming to targetthe cells and tissues to produce anticipated pharmacological action. The aim of the present study was to formulate and evaluate rivastigmine (RT) loaded chitosan (CS) nanoparticles for sustained release. RT is a short actingreversible acetylcholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's and Parkinson's disease. In current research RT loaded CS-tripolyphosphate (TPP) nanoparticles were prepared by usingionic gelation method in fourdifferent polymer concentrations (0.1%,0.2%,0.3%,0.4%). The prepared nanoparticles were evaluated by Zeta sizer in order to determine particle size, PDI and zeta potential. Further, drug entrapment efficiency and in vitro release studies were carried out. The results showed that particle size decreased by loading drug within nanoparticles when compared with unloaded nanoparticles. The particle size of RT loaded CS nanoparticles ranged from 125.9 ± 2.5 to 356.0 ± 7.9 by varying CS concentration from 0.1% to 0.4% w/v. Among different ratios studied, 0.4% ratio showed highest drug entrapment efficiency (80%). In vitro release studies showed that RT loaded CS nanoparticles could sustain release the drug.In conclusion, the current research results showed that the chitosan nanoparticles can be used as a potential carrier for providing sustained delivery of RT.

Brain targeted delivery of sumatriptan succinate loaded chitosan nanoparticles: Preparation, In vitro characterization, and (Neuro-)pharmacokinetic evaluations

Migraine is a neurovascular disorder characterized by nausea, vomiting, pain, photophobia, phonophobia, and in some cases auras. Because of the complexity of the pathophysiology of migraine and the limited systemic availability of sumatriptan succinate after oral administration, oral delivery of sumatriptan succinate encountered with important limitations. During this study formulation and evaluation of the neuropharmacokinetics of intravenous and intranasal (IN)-administered sumatriptan succinate-loaded chitosan nanoparticles were considered. At first, formulation and characterization of drug-loaded chitosan nanoparticles were performed and then neuropharmacokinetic parameters including direct transport percentage (DTP) and drug targeting efficiency (DTE) were assessed by performing an in vivo study on rats. Ionic gelation technique led to the preparation of nanoparticles with 105 nm mean diameter and polydispersity index (PDI) of 0.38. The drug entrapment efficiency (EE) for the nanoparticles was calculated 59.60 ± 2.12%. In vitro release study indicated that 12 and 32% of the drug were released in the first 1 and 4 h after the beginning of the experiment. DTE and DTP of IN-administered nanoparticles were calculated 493.39% and 79.79%, respectively. Neuropharmacokinetic evaluations of the polymeric nanoparticles represent a suitable brain delivery system. The high DTP value for nanoparticles confirms the satisfactory entrance of the drug into the higher parts of the brain.

Preparation and characterization of sodium alginate/polyvinyl alcohol hydrogel containing drug-loaded chitosan nanoparticles as a drug delivery system

In this study, an optimal combination of sodium alginate (SA)/polyvinyl alcohol (PVA) hydrogel containing Rosuvastatin-loaded chitosan (CS) nanoparticles was fabricated as the drug delivery system (DDS). First, the drug-loaded nanoparticles were synthesized by the ionic gelation method. Then, several hydrogel films with different ratios of SA:PVA were prepared. Subsequently, different concentrations of drug-loaded CS nanoparticles were added to a hydrogel with an optimal SA:PVA ratio. The results of the tensile test showed that in the SA:PVA ratio of 7:3 and 3 wt % of drug-loaded CS nanoparticles, the hydrogel film was achieved with optimal mechanical properties. The mean size of drug-loaded CS nanoparticles determined by the AFM and DLS methods was in the range of approximately 100–150 nm. The release profile of the Rosuvastatin drug from the fabricated DDS illustrated that all the loaded drug was released within 24 h, and the CS nanoparticles had a significant effect on the release behavior. Also, the cytotoxicity of the fabricated DDS on the human fibroblast cells demonstrated a high cell viability after 72 h of incubation. Therefore, the fabricated SA/PVA hydrogel containing drug-loaded CS nanoparticles depicted a great potential as the delivery system for the controlled release of the Rosuvastatin drug.

On physical and antibacterial properties and drug release behavior of poly(vinyl alcohol) hydrogels: effect of drug loaded chitosan nanoparticles

ABSTRACTThis paper deals with influence of chitosan nanoparticles (CNPs) loaded by tetracycline, as a drug, on the physico-mechanical and antibacterial properties as well as drug release behavior of poly(vinyl alcohol), PVA, hydrogels prepared by electron beam irradiation. The formation of spherical chitosan particles in nanoscale size prepared by an ionic gelation method was confirmed by FTIR and UV spectroscopy, and scanning electron microscopy analyses. The drug release kinetic studies from drug loaded chitosan nanoparticles (DLCNPs) at pH = 7.4 revealed a linear and steady release behavior over long period of time. The theoretical analysis of the swelling kinetic data, using Peppas’s model showed that the swelling kinetic is governed by Fickian diffusion for all the prepared hydrogels, however, the water diffusion coefficient, and therefore, the swelling content were lower for the hydrogels loaded with DLCNPs as compared to the ones with the neat drug. In agreement with these results, the hydrogels containing DLCNPs exhibited a more controlled drug release behavior with significantly stronger antibacterial activity. The tensile mechanical properties of the hydrogels not affected by the DLCNPs were found to be suitable for wound dressing applications.

A pH-Mediated Electronic Wound Dressing for Controlled Drug Delivery.

Topical administration of drugs in a timely manner according to the physiological need at the wound site can enhance the healing rate of chronic wounds. Herein, an electronic wound dressing that enables active topical drug delivery in response to electrically induced pH change is demonstrated for potential treatment of chronic wounds. In this platform, the pH of the dressing is controlled using an electrical field. This allows precise electrical control over the temporal profile of pH-mediated drug release. This engineered dressing is comprised of microfabricated electrodes serving as anode and cathode, a pH sensitive hydrogel, and controlled electronic circuitry. The anode is coated with a pH sensitive poly(ethylene glycol)-diacrylate/Laponite hydrogel layer containing drug loaded chitosan nanoparticles (ChPs). Applying a DC voltage between the electrodes results in a local change in pH near the electrodes. In basic environments found near the anode, the ChPs release their drug due to the dehydration process, while in acidic environments the release profile is negligible. Turning off the DC voltage results in immediate pH recovery and cessation of drug release. The biocompatibility of the dressing has also been confirmed-the pH shift resulting from application of DC voltage does not affect the wound pH significantly.

Advances and Potential Applications of Chitosan Nanoparticles as a Delivery Carrier for the Mucosal Immunity of Vaccine.

Drug research and development has entered into the new epoch of innovation formulation, and the drug delivery system has been in the forefront of pharmaceutical innovation. Chitosan, a natural polysaccharide derived from chitin, due to its well-known biocompatibility and biodegradability, it has been widely used in drug delivery, immunostimulation, tissue regeneration, blood coagulation, wound healing, drug delivery and tissue engineering. Chitosan has become a valuable vaccine adjuvant and delivery carrier, which have attracted increasing attention for its applications. In this paper, we reviewed chitosan nanoparticles, which is a promising biomaterial as vaccine adjuvant and delivery carrier, including characteristics, preparation methods and applications, or even its limitations. We also investigated the mucosal immune delivery route for drug loaded chitosan nanoparticles, such as the routes of oral and nasal. Due to the low toxicity, better biodegradability and adhesivity of chitosan nanoparticles, it can be used as the delivery carrier of vaccine antigens and drugs. These promising studies laid a foundation for the applications of chitosan nanoparticles as a delivery carrier in the vaccine or drug. We undertook a structured research of biodegradable polymeric nanoparticles of chitosan used as a delivery carrier for the mucosal immunity of vaccine. We have searched the bibliographic databases for peer-reviewed research literature. The outstanding characteristics of the screened papers were described respectively, and a systematic content analysis methodology was used to analyse the findings. Sixty-three papers were included in the review, the majority defined leadership and governance approaches that had impacted upon the polymeric nanoparticles as the delivery carrier for the mucosal immunity of vaccine in therapeutic applications and developments. Thirty-five papers outlined the superiority characteristics of chitosan nanoparticles that applied in the field of vaccine. Twenty-eight papers overviewed the application prospects of chitosan derivatives used as drug delivery systerm. These included current advances in research and clinical applications of chitosan derivatives. This review identified the drug delivery systerm of chitosan or its derivatives, and we described the synthesis methods, applications and challenges of chitosan. The findings of this review identified that the chitosan derivatives were used as delivery carrier for vaccines. It also indicates that the chitosan or its derivatives play a vital role in the drug and vaccine delivery systerm.

Phenylboronic Acid-Mediated Tumor Targeting of Chitosan Nanoparticles

The phenylboronic acid-conjugated chitosan nanoparticles were prepared by particle surface modification. The size, zeta potential and morphology of the nanoparticles were characterized by dynamic light scattering, zeta potential measurement and transmission electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using monolayer cell model, 3-D multicellular spheroid model and H22 tumor-bearing mice. The incorporation of phenylboronic acid group into chitosan nanoparticles impart a surface charge-reversible characteristic to the nanoparticles. In vitro evaluation using 2-D and 3-D cell models showed that phenylboronic acid-decorated nanoparticles were more easily internalized by tumor cells compared to non-decorated chitosan nanoparticles, and could deliver more drug into tumor cells due to the active targeting effect of boronic acid group. Furthermore, the phenylboronic acid-decorated nanoparticles displayed a deeper penetration and persistent accumulation in the multicellular spheroids, resulting in better inhibition growth to multicellular spheroids than non-decorated nanoparticles. Tumor penetration, drug distribution and near infrared fluorescence imaging revealed that phenylboronic acid-decorated nanoparticles could penetrate deeper and accumulate more in tumor area than non-decorated ones. In vivo antitumor examination demonstrated that the phenylboronic acid-decorated nanoparticles have superior efficacy in restricting tumor growth and prolonging the survival time of tumor-bearing mice than free drug and drug-loaded chitosan nanoparticles.

Dual drug loaded chitosan nanoparticles—sugar-coated arsenal against pancreatic cancer

Pancreatic cancer is an aggressive form of cancer with poor survival rates. The increased mortality due to pancreatic cancer arises due to many factors such as development of multidrug resistance, presence of cancer stem cells, development of a stromal barrier and a hypoxic environment due to hypo-perfusion. The present study aims to develop a nanocarrier for a combination of drugs that can address these multiple issues. Quercetin and 5-fluorouracil were loaded in chitosan nanoparticles, individually as well as in combination. The nanoparticles were characterized for morphology, size, zeta potential, percentage encapsulation of drugs as well as their release profiles in different media. The dual drug-loaded carrier exhibited good entrapment efficiency (quercetin 95% and 5-fluorouracil 75%) with chitosan: quercetin: 5-fluorouracil in the ratio 3:1:2. The release profiles suggest that 5-fluorouracil preferentially localized in the periphery while quercetin was located towards the core of chitosan nanoparticles. Both drugs exhibited considerable association with the chitosan matrix. The dual drug-loaded carrier system exhibited significant toxicity towards pancreatic cancer cells both in the 2D as well as in the 3D cultures. We believe that the results from these studies can open up interesting options in the treatment of pancreatic cancer.

Catharanthus roseus leaf extract-synthesized chitosan nanoparticles for controlled in vitro release of chloramphenicol and ketoconazole

We report the size-controlled chitosan nanoparticles synthesized by Catharanthus roseus leaf extract-mediated cross-linking of chitosan. Optimization of pH, ratio of chitosan to leaf filtrate concentration, and cross-linking time was performed for designing factorial synthetic strategy, which revealed minimum diameter (45 nm) of chitosan nanoparticles at pH 3 by employing chitosan/leaf extract in the ratio 3:1. The biogenically synthesized chitosan nanoparticles were further explored for encapsulation and controlled release of ketoconazole and chloramphenicol. The resulting drug-loaded chitosan nanoparticles showed size-dependent drug entrapment efficiency of 82.88 and 78.96 % with drug-loading capacity of 41.44 and 39.48 % for chloramphenicol and ketoconazole, respectively. The cumulative in vitro drug release up to 12 h was achieved which suggests enhanced efficacy of green synthesized chitosan nanoparticles for therapeutic and drug delivery applications. So far, there is no report concerning biogenic synthesis of chitosan nanoparticles; hence, it is being reported for the first time.

Formulation and characterization of Anti alzheimer’s drug loaded chitosan nanoparticles and its in vitro biological evaluation

<p style="text-align: justify;"><strong>Objective:</strong> The main objective of the study is to formulate hydrophilic drug loaded sustained release nanoparticles with the size of 200 nm and to increase the encapsulation efficiency of the drug. <strong>Methodology:</strong> The nanoparticles were prepared by simple ionic gelation method using various concentrations of chitosan and TPP. The prepared nanoparticles were evaluated for particle size, shape, charge, encapsulation efficiency,<em> in vitro </em>drug release and in vitro cytotoxicity. <strong>Results:</strong> The optimized drug loaded nanoparticles showed the size of 125 &plusmn; 4mn with PDI 0.25 &plusmn; 0.05, potential of +40 &plusmn; 2 mV, encapsulation efficiency of 65.5 &plusmn; 1.2% and the drug release of 68.4 &plusmn; 1.6% with an initial burst effect up to one hour followed by sustained release up to 24 hrs. Further the optimized formulation was subjected to investigate the cytotoxicity of CS-NP in SH-SY-5Y cell lines it revealed that the cell viability was above 90% without any toxicity. <strong>Conclusion:</strong> These preliminary results demonstrate that the possibility of delivering hydrophilic drugs to brain with enhanced encapsulation efficiency. <p style="text-align: justify;"><strong>Key words:</strong> Chitosan, Hydrophilic drugs, Nanoparticles, Cytotoxicity, Blood brain barrier.

Formulation and Evaluation of Enteric Coated Nanoparticulate System for Poorly Absorbable Drug

The research work was aimed to develop mucoadhesive nanoparticulate system for enhancing solubility and bioavailability of poorly soluble drug, simvastatin (SVS) (model drug). The nanoparticles (NPs) suspensions were prepared by ionotropic gelation method using chitosan (CS), sodium tripolyphosphate(STPP), β-cyclodextrin (β-CD) and coated with Eudragit L100. The CS NPs were characterized by DSC, FTIR, SEM, zeta potential and evaluated for entrapment efficiency, drug loading, in vitro drug release, ex vivo study and mucoadhesive strength. The results showed that the STPP/CS ratio 1:5 produced particles in nanorange and the size of the drug loaded CS NPs were not affected by the incorporation of β-CD. As the β-CD: drug ratio increased the final drug loading increased significantly. The in vitro study showed initial burst release followed by delayed release. The ex vivo study revealed increased drug transport from CS NPs through rat intestinal mucus lining. In conclusion, this new nanosystem seems to be promising carriers for transmucosal delivery of drugs having poor solubility and bioavailability.

Permeability of exendin-4-loaded chitosan nanoparticles across MDCK cell monolayers and rat small intestine.

The purpose of this study was to investigate the permeability of exendin-4-loaded chitosan nanoparticles using the Madin Darby canine kidney (MDCK) cell monolayer as an in vitro model and the rat intestine as an ex vivo model of the human intestinal barrier. A series of formulations of sodium tripolyphosphate (TPP) and chitosan with different molecular weights and degrees of deacetylation was evaluated. The formulation consisting of 0.1% TPP and 0.2% chitosan (400 kDa, 95% degree of deacetylation), which gave optimized monodispersed particle size (303.1±10.36 nm), zeta potential (18.37±1.15 mV) and encapsulation efficiency (38.0±2.6%), was used for further analysis. After determining their biocompatibility, the transport potential of drug-loaded chitosan nanoparticles was evaluated and compared with free exendin-4 using both MDCK cell monolayers and different rat intestinal segments. Mechanisms underlying enhanced transport of exendin-4 in the cell model were also explored. Compared with free exendin-4, the absorption of optimized chitosan nanoparticles was enhanced by 4.7-fold in MDCK cell monolayers and by 2.0-2.78-fold in different rat intestinal segments, with no significant difference between the duodenum, jejunum and ileum. As supported by confocal laser scanning microscopic analysis, the lower enhancement of absorption in the intestine compared to the cell monolayer likely resulted from the chitosan nanoparticle-mediated opening of cellular tight junctions and not through intracellular transport. These findings suggest that the potential application of chitosan nanoparticles as delivery carriers of exendin-4 is limited and may need further modifications.

Spinning Disc Processing Technology: Potential for Large-Scale Manufacture of Chitosan Nanoparticles

Mass production of nanoparticles using a reliable cost-effective approach is a challenge in the pharmaceutical industry. In this study, the spinning disc processing (SDP) technology was used to fabricate chitosan nanoparticles, with a view to commercially produce chitosan nanoparticle-based drug delivery platforms. Chitosan solution (0.25%, w/v, in dilute acid, 27.5 mL, 1.5 mL/s) was intensely mixed with sodium tripolyphosphate solution (0.10%, w/v, in water, 20 mL, 1.1 mL/s) on the spinning disc (1000 rpm). Transmission electron microscopy and dynamic light scattering data confirmed that the nanoparticles (20 +/- 3 nm) were comparable in size and shape to those synthesised using a beaker and magnetic stirrer (31 +/- 13 nm). Larger nanoparticles (131 +/- 5 nm) were produced by increasing the chitosan and TPP feed concentrations to 0.5% and 0.125%, respectively. Drug loading further increased the size of the nanoparticles, with N-acetyl cysteine (NAC) having a greater effect (403 +/- 4 nm) than paracetamol (165 +/- 4 nm). Co-loading of both drugs increased the size of the particles to the micron range. In conclusion, the SDP is a robust technology capable of expanding the production of blank and drug-loaded chitosan nanoparticles for the biomedical and pharmaceutical industries.

Preparation of aspirin and probucol in combination loaded chitosan nanoparticles and in vitro release study

We design and develop chitosan nanoparticles which load two different drugs simultaneously. Aspirin (acetylsalicylic acid, ASA), a hydrophilic drug and probucol (PRO), a hydrophobic drug, are chosen as typical drugs, which are widely used to treat restenosis. The drug loaded chitosan nanoparticles are prepared by gelation of chitosan with tripolyphosphate (TPP) by ionic cross-linking. The physicochemical properties of nanoparticles are investigated by FTIR, transmission electron microscope (TEM), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The images show that these particles are spherical in shape with ASA being in the amorphous phase, while PRO is crystalline. The properties of chitosan nanoparticles such as encapsulation capacity and controlled release behaviors of ASA and PRO are evaluated. Experimental results indicate that the loading capacity (LC), encapsulation efficiency (EE) and ASA and PRO release behaviors are affected by several factors including pH, concentration of TPP, chitosan molecular weight (MW) and ASA initial concentration as well as PRO. In vitro release shows that the nanoparticles provide a continuous release. Entrapped ASA is released for more than 24 h and PRO lasts longer for 120 h.