Synthesis and Characterization of Chitosan Tripolyphosphate Nanoparticles and its Encapsulation Efficiency Containing Russell's Viper Snake Venom

Chitosan Tripolyphosphate (CS/TPP) nanoparticle is a biodegradable and nontoxic polysaccharide, used as a carrier for drug delivery. The morphology and particle‐size measurements of the nanoparticles were studied by field emission scanning electron microscopy and Fourier Transform Infrared Spectroscopy (FTIR). This study aims to evaluate the impact of Russell's viper venom encapsulation on various factors and loading capacity, in addition to explore the physicochemical structure of nanoparticles. FTIR confirmed that tripolyphosphoric groups of TPP linked with ammonium groups of CS in the nanoparticles. Our results showed that CS can react with TPP to form stable cationic nanoparticles. The results also showed that encapsulation efficiency of venom at different concentrations of 20, 40, 60, 500, and 1000 µg/mL were achieved for CS/TPP nanoparticles at different concentrations of 1.5, 2, and 3 mg/mL. The cytotoxicity of CS/TPP nanoparticles was evaluated by MTT (‐3 (4, 5‐Dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide, a tetrazole) assay. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:406‐411, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21502     

Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery

Nanoparticles of approximately 10nm in diameter made with chitosan or lactic acid-grafted chitosan were developed for high drug loading and prolonged drug release. A drug encapsulation efficiency of 92% and a release rate of 28% from chitosan nanoparticles over a 4-week period were demonstrated with bovine serum protein. To further increase drug encapsulation, prolong drug release, and increase chitosan solubility in solution of neutral pH, chitosan was modified with lactic acid by grafting D,L-lactic acid onto amino groups in chitosan without using a catalyst. The lactic acid-grafted chitosan nanoparticles demonstrated a drug encapsulation efficiency of 96% and a protein release rate of 15% over 4 weeks. With increased protein concentration, the drug encapsulation efficiency decreased and drug release rate increased. Unlike chitosan, which is generally soluble only in acid solution, the chitosan modified with lactic acid can be prepared from solutions of neutral pH, offering an additional advantage of allowing proteins or drugs to be uniformly incorporated in the matrix structure with minimal or no denaturization.     

青蒿琥酯纳米颗粒的制备及其体外抑制肿瘤细胞增殖的作用研究

目的：用壳聚糖（Chitosan,CS）和三聚磷酸钠（tripolyphosphate,TPP）交联制备包载青蒿琥酯纳米粒,并探讨其在体外对肿瘤细胞增殖的抑制作用。方法：以壳聚糖-三磷酸钠（CS／TPP）为基质并优化其比例,采用离子凝胶法制备包载青蒿琥酯（ART）纳米粒,对其进行表征包括粒径大小、Zeta电位、包封率、载药量和体外释放试验,以及红外光谱分析。用MTT法检测包栽青蒿琥酯的壳聚糖·三磷酸钠纳米粒对Hela、Caski、U251、MCF-7和HepG2细胞增殖的抑制作用。结果：成功构建青蒿琥酯一壳聚糖．三磷酸钠纳米颗粒（ARTnanoparticals,ART-NPs）,平均粒径为166．8±0．2nnl,电位为10．2±0．79mV,红外光谱分析表明CS厂rPP成功连接并包裹ART,平均载药量和包封率分别为18％和74．82％;体外释放呈典型的双相分布,前24h呈暴发性释放（44．2％）,其后缓慢释放,第9天累积释放度达67．4％。对不同肿瘤细胞的杀伤作用呈浓度和时间依赖趋势,且ART-NPs作用优于单-ART;相同浓度的ART-NPs在96h时对细胞增殖的抑制率明显高于ART组（P〈O．05）。结论：用壳聚糖和三磷酸钠交联可成功包载青蒿琥酯制成具有缓释性的纳米制剂,对肿瘤细胞的生长具有明显的抑制作用,有潜在的肿瘤治疗价值。     

Effect of Formulation and Process Parameters on Chitosan Microparticles Prepared by an Emulsion Crosslinking Technique

There are many studies about the synthesis of chitosan microparticles; however, most of them have very low production rate, have wide size distribution, are difficult to reproduce, and use harsh crosslinking agents. Uniform microparticles are necessary to obtain repeatable drug release behavior. The main focus of this investigation was to study the effect of the process and formulation parameters during the preparation of chitosan microparticles in order to produce particles with narrow size distribution. The technique evaluated during this study was emulsion crosslinking technique. Chitosan is a biocompatible and biodegradable material but lacks good mechanical properties; for that reason, chitosan was ionically crosslinked with sodium tripolyphosphate (TPP) at three different ratios (32, 64, and 100%). The model drug used was acetylsalicylic acid (ASA). During the preparation of the microparticles, chitosan was first mixed with ASA and then dispersed in oil containing an emulsifier. The evaporation of the solvents hardened the hydrophilic droplets forming microparticles with spherical shape. The process and formulation parameters were varied, and the microparticles were characterized by their morphology, particle size, drug loading efficiency, and drug release behavior. The higher drug loading efficiency was achieved by using 32% mass ratio of TPP to chitosan. The average microparticle size was 18.7 μm. The optimum formulation conditions to prepare uniform spherical microparticles were determined and represented by a region in a triangular phase diagram. The drug release analyses were evaluated in phosphate buffer solution at pH 7.4 and were mainly completed at 24 h.     

In Vitro and In Vivo Studies on Chitosan Beads of Losartan Duolite AP143 Complex, Optimized by Using Statistical Experimental Design

The aim of the present research work was to develop release modulated beads of losartan potassium complexed with anion exchange resin, Duolite AP143 (cholestyramine). Chitosan was selected as a hydrophilic polymer for the formation of beads which could sustain the release of the drug up to 12 h, along with drug resin complex (DRC). Chitosan beads were prepared using an in-liquid curing method by ionotropic cross-linking or interpolymer linkage with sodium tripolyphosphate (TPP). The formulation of the beads was optimized for entrapment efficiency and drug release using 3² full factorial design. The independent variables selected were DRC/chitosan and percent of TPP. The optimization model was validated for its performance characteristics. Studies revealed that as the concentration of chitosan and TPP was increased, entrapment efficiency and the drug release were found to increase and decrease, respectively. The swelling capacity of chitosan–TPP beads decreased with increasing concentration of TPP. The effect of chitosan concentration and percentage of TPP solution used for cross-linking on entrapment efficiency and drug release rate was extensively investigated. Optimized beads were subjected to in vivo studies in Wistar albino rats to determine the mean arterial blood pressure and compared with marketed formulation. The pharmacodynamic study demonstrates steady blood pressure control for optimized formulation as compared to fluctuated blood pressure for the marketed formulation.     

Polyelectrolyte nanoparticles based on water-soluble chitosan-poly(l-aspartic acid)-polyethylene glycol for controlled protein release

Water-soluble chitosan (WSC)-poly(l-aspartic acid) (PASP)-polyethylene glycol (PEG) nanoparticles (CPP nanoparticles) were prepared spontaneously under quite mild conditions by polyelectrolyte complexation. These nanoparticles were well dispersed and stable in aqueous solution, and their physicochemical properties were characterized by turbidity, FTIR spectroscopy, dynamic light scattering (DLS), transmission electron microscope (TEM), and zeta potential. PEG was chosen to modify WSC-PASP nanoparticles to make a protein-protective agent. Investigation on the encapsulation efficiency and loading capacity of the bovine serum albumin (BSA)-loaded CPP nanoparticles was also conducted. Encapsulation efficiency was obviously decreased with the increase of initial BSA concentration. Furthermore, its in vitro release characteristics were evaluated at pH 1.2, 2.5, and 7.4. In vitro release showed that these nanoparticles provided an initial burst release, followed by a slowly sustained release for more than 24 h. The BSA released from CPP nanoparticles showed no significant conformational change compared with native BSA, which is superior to the BSA released from nanoparticles without PEG. A cell viability study suggested that the nanoparticles had good biocompatibility. This nanoparticle system was considered promising as an advanced drug delivery system for the peptide and protein drug delivery.     

壳聚糖-有机累托石/海藻酸钠复合纳米粒的制备

目的:以BSA作为模型药物,制备壳聚糖季铵盐-OREC复合物纳米微粒,建立一种安全有效的药物控释传递系统。方法:超声条件下,制备不同质量比的具有壳聚糖硅酸盐插层结构的复合物纳米微粒,观察其形态学特征、进行红外光谱分析。同时,测定OREC对BSA包封率和载药量的影响。结果:成功制备了不同质量比的OREC-HTCC纳米粒子。电镜结果显示纳米粒呈圆球形,均匀,平均粒径约为30nm。红外图谱分析证实,HTCC插入了OREC插层中,BSA成功地包裹入HTCC-ALG/OREC混合材料制备的纳米微粒。加入OREC后,纳米粒子的包封率及载药量均明显提高,但随着加入量的增加,包封率及载药量逐渐减少。结论:OREC-HTCC纳米粒子是良好的蛋白药物载体,具有粒径小、包封率高、缓释效果好等优点,为CS-OREC作为潜在的药物给药系统的进一步应用提供科学依据。     

An investigation on the short-term biodegradability of chitosan with various molecular weights and degrees of deacetylation

Research efforts have been devoted to demonstrating that the pH-sensitive characteristics of poly NIPAAm/chitosan nanoparticles can be applied to targeting tumors. A copolymer of (NIPAAm) and chitosan (4:1, m/m) was synthesized, and its drug release characteristics investigated. The results revealed that drug-loaded nanoparticles which encapsulation and loading efficiencies were 85.7% and 9.6%, respectively, exhibited pH-sensitive responses to tumor pH. The cumulative release rate was significantly enhanced below pH 6.8 and decreased rapidly above pH 6.9 at 36.5 ± 0.5 °C. MTT assay and fluorescence microscopic study showed that drug release was drastically promoted in tumor surroundings while exerting less effect in normal conditions. For mice treated with nanoparticles, the decrease in body weight was limited, and significant tumor regression was observed with complete regression in more than 50% of the mice. The life span of tumor-bearing mice was significantly increased when they were treated with nanoparticles. Thereby, the super pH-sensitive poly NIPAAm/chitosan nanoparticles may provide outstanding advantages for anti-cancer drug delivery.     

Applying the Taguchi Design for Optimized Formulation of Sustained Release Gliclazide Chitosan Beads: An In Vitro/In Vivo Study

Gliclazide is a second generation of hypoglycemic sulfonylurea and acts selectively on pancreatic β cell to control diabetes mellitus. The objective of this study was to produce a controlled release system of gliclazide using chitosan beads. Chitosan beads were produced by dispersion technique using tripolyphosphate (TPP) as gelating agent. The effects of process variables including chitosan molecular weight, concentration of chitosan and TPP, pH of TPP, and cross-linking time after addition of chitosan were evaluated by Taguchi design on the rate of drug release, mean release time (MRT), release efficiency (RE₈%), and particle size of the beads. The blood glucose lowering effect of the beads was studied in normal and streptozotocin-diabetic rats. The optimized formulation CL₂T₅P₂t₁₀ with about 31% drug loading, 2.4 h MRT, and 69.16% RE₈% decreased blood glucose level in normal rats for 24 h compared to pure powder of gliclazide that lasted for just 10 h.     

Preparation,structure, drug release and bioinspired mineralization of chitosan-based nanocomplexes for bone tissue engineering

Chitosan-based nanocomplexes with various forms were prepared by ionically crosslinking with tripolyphosphate (TPP) in different acidic media under mild conditions. It was found that the self-assembly and ionic interactions of chitosan and TPP were greatly affected by reaction media, and chitosan-based nanofibers could be obtained in adipic acid medium while nanoparticles were formed in acetic acid medium. Using bovine serum albumin (BSA) as a macromolecular model-drug, in vitro drug release studies indicated that chitosan-based nanofibers and nanoparticles exhibited a similar prolonged release profile. In addition, the bioinspired mineralization of both chitosan-based nanofibers and nanoparticles was carried out by soaking them in synthetic body fluids (SBF). Transmission electron microscopy (TEM) and X-ray Diffraction (XRD) results indicated that chitosan-based nanofibers have better inductivity for nano-hydroxyapatite formation than chitosan-based nanoparticles. The results suggested that biomimetic chitosan-based nanofibers with controlled release capacity of bioactive factors may be of use in bone tissue engineering for enhancing the bioactivity and bone inductivity.     

Biopolymer nanoparticle production for controlled release of biopharmaceuticals

Abstract

For drug applications, nanoparticles, used as drug carriers, offer the advantage of controlled release, therapeutic impact and targeted delivery. In drug delivery applications, biodegradable polymers can be extracted from natural sources or prepared synthetically by polymerization. Natural polymers typically have varying compositions and physiochemical properties. As a result, methods which utilize natural polymers to encapsulate drugs are more varied and polymer dependent. The following polymers are discussed in this review article: alginate, chitosan, gelatin, albumin, gliadin, pullulan, and dextran. Specialized encapsulation nanotechnologies will be discussed such as ionotropic gelation, complexation, the reverse microemulsion technique, cross-linking methods, emulsion-dependent methods, desolvation methods and self-assembly methods. For each biopolymer an overview of the structure is presented with the corresponding encapsulation techniques. Understanding the structure of the biopolymer is important as to not only understand the rational for current encapsulation techniques but to continue to develop new encapsulation techniques in pursuit of the ideal drug carrier for application in therapeutic treatments.     

Enhanced anti-topoisomerase II activity by mucoadhesive 4-CBS–chitosan/poly (lactic acid) nanoparticles

In this study, the biodegradable mucoadhesive 4-carboxybenzensulfonamide chitosan (4-CBS–chitosan)/poly (lactic acid) (PLA) nanoparticles were fabricated by the electrospray ionization technique for enhancing anti-topoisomerase II (Topo II) activity. The obtained (4-CBS–chitosan/PLA)-DOX nanoparticles were characterized using SEM, particle size analyzer. We emphasis on encapsulation efficiency, in vitro drug release behavior and also performed in vitro studies of Topo II inhibitory activity using gel electrophoresis. In addition, the cytotoxicity of the 4-CBS–chitosan/PLA nanoparticles using MTT assay was also studied. The mean particle size of spherical shaped (4-CBS–chitosan/PLA)-DOX is less than 300 nm. The DOX loaded 4-CBS–chitosan/PLA composite nanoparticles produced high entrapment efficiency of 85.8% and provided the prolonged release of DOX extended to 26 days and also still had strong Topo II inhibitory activity up to 77.4%. Overall, it was shown that 4-CBS–chitosan/PLA nanoparticles could be promising carriers for controlled delivery of anticancer drugs.     

A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluations

Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20–25 μm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit’s eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye.     

Electrospinning of Cross-Linked Magnetic Chitosan Nanofibers for Protein Release

A poly(vinylalcohol) (PVA) electrospun/magnetic/chitosan nanocomposite fibrous cross-linked network was fabricated using in situ cross-linking electrospinning technique and used for bovine serum albumin (BSA) loading and release applications. Sodium tripolyphosphate (TPP) and glutaraldehyde (GA) were used as cross-linkers which modified magnetic-Fe₃O₄ chitosan as Fe₃O_4/CS/TPP and Fe₃O_4/CS/GA, respectively. BSA was used as a model protein drugs which was encapsulated to form Fe₃O₄/CS/TPP/BSA and Fe₃O₄/CS/GA/BSA nanoparticles. The composites were electrospun with PVA to form nanofibers. Nanofibers were characterized by field emission scanning electron microscopy (FESEM) and Fourier transform infrared spectroscopy (FTIR). The characterization results suggest that Fe₃O₄ nanoparticles with average size of 45 nm were successfully bound on the surface of chitosan. The cross-linked nanofibers were found to contain uniformly dispersed Fe₃O₄ nanoparticles. The size and morphology of the nanofibers network was controlled by varying the cross-linker type. FTIR data show that these two polymers have intermolecular interactions. The sample with TPP cross-linker showed an enhancement of the controlled release properties of BSA during 30-h experimental investigation.

Graphical Abstract

Open in a separate windowᅟKEY WORDS: cross-linker, electrospun, magnetite, mano-composite, protein loading     

Chitosan microcapsules loaded with either miconazole nitrate or clotrimazole,prepared via emulsion technique

In this paper, a simple and versatile coacervation technique has been developed by using an ultrasound-assisted oil/water emulsion method for the preparation of antifungal agent-loaded microcapsules. Two types of chitosan microcapsules are successfully prepared. The mean particle size of the chitosan/miconazole nitrate microcapsules is 2.6 μm and that of the chitosan/clotrimazole microcapsules is 4.1 μm. The encapsulation efficiency of the chitosan/miconazole nitrate microcapsules (77.58–96.81%) is relatively higher than that of the chitosan/clotrimazole microcapsules (56.66–93.82%). The in vitro drug release performance of the microcapsules shows that the chitosan/miconazole nitrate microcapsules release about 49.5% of the drug while chitosan/clotrimazole microcapsules release more than 66.1% of the drug after 12 h under a pressure of 5 kg at pH 5.5, which is similar to the pH of human skin. The prepared drug-loaded microcapsules could be applied onto bandages or socks, and will continuously release antifungal drugs in a controlled manner under pressure.     

Facile preparation of well-defined near-monodisperse chitosan/sodium alginate polyelectrolyte complex nanoparticles (CS/SAL NPs) via ionotropic gelification: A suitable technique for drug delivery systems

Polymeric nanoparticles have emerged as a promising approach for drug delivery systems. We prepared chitosan (CS)/sodium alginate (SAL) polyelectrolyte complex nanoparticles (CS/SAL NPs) via a simple and mild ionic gelation method by adding a CS solution to a SAL solution, and investigated the effects of molecular weight of the added CS, and the SAL:CS mass ratio on the formation of the polyelectrolyte complex nanoparticles. The well-defined CS/SAL NPs with near-monodisperse particle size of about 160 nm exhibited a pH stable structure, and pH responsive properties with a negatively or positively charged surface. The so-called “electrostatic sponge” structure of the polyelectrolyte complex nanoparticles enhanced their drug-loading capacity towards the differently charged model drug molecules, and favored controlled release. We also found that the drug-loading capacity was influenced by the nature of the drugs and the drug-loading media, while drug release was affected by the solubility of the drugs in the drug-releasing media. The biocompatibility and biodegradability of the polyelectrolytes in the polyelectrolyte complex nanoparticles were maintained by ionic interactions. These results indicate that CS/SAL NPs can represent a useful technique for pH-responsive drug delivery systems.     

Evaluation of chitosan nanoformulations as potent anti-HIV therapeutic systems

Background

Antiretroviral Therapy (ART) is currently the major therapeutic intervention in the treatment of AIDS. ART, however, is severely limited due to poor availability, high cytotoxicity, and enhanced metabolism and clearance of the drug molecules by the renal system. The use of nanocarriers encapsulating the anti-retroviral drugs may provide a solution to the aforementioned problems. Importantly, the application of mildly immunogenic polymeric carrier confers the advantage of making the nanoparticles more visible to the immune system leading to their efficient uptake by the phagocytes.

Methods

The saquinavir-loaded chitosan nanoparticles were characterized by transmission electron microscopy and differential scanning calorimetry and analyzed for the encapsulation efficiency, swelling characteristics, particle size properties, and the zeta potential. Furthermore, cellular uptake of the chitosan nanocarriers was evaluated using confocal microscopy and Flow cytometry. The antiviral efficacy was quantified using viral infection of the target cells.

Results

Using novel chitosan carriers loaded with saquinavir, a protease inhibitor, we demonstrate a drug encapsulation efficiency of 75% and cell targeting efficiency greater than 92%. As compared to the soluble drug control, the saquinavir-loaded chitosan carriers caused superior control of the viral proliferation as measured by using two different viral strains, NL4-3 and Indie-C1, and two different target T-cells, Jurkat and CEM-CCR5.

Conclusion

Chitosan nanoparticles loaded with saquinavir were characterized and they demonstrated superior drug loading potential with greater cell targeting efficiency leading to efficient control of the viral proliferation in target T-cells.

General significance

Our data ascertain the potential of chitosan nanocarriers as novel vehicles for HIV-1 therapeutics.     

Chitosan and silver nanoparticles are attractive auxin carriers: A comparative study on the adventitious rooting of microcuttings in apple rootstocks

Nanocarriers for encapsulation and sustained release of agrochemicals such as auxins have emerged as an attractive strategy to provide enhanced bioavailability and efficacy for improved crop yields and nutrition quality. Here, a comparative study was conducted on the effectiveness of chitosan-as a biopolymeric nanocarrier- and silver-as a metallic nanocarrier- on in vitro adventitious rooting potential of microcuttings in apple rootstocks, for the first time. Auxins indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) loaded silver (nAg) or chitosan nanoparticles (nChi) were synthesized. Scanning electron microscopy and transmission electron microscopy studies showed the spherical shape of the nanoparticles. The average particle size of IAA-nChi was 167.5 ± 0.1 nm while that of IBA-nChi was 123.2 ± 2.6 nm. The hydrodynamic diameter of the nAg-IAA and nAg-IBA particles were measured as 93.66 ± 5 nm and 71.41 ± 3 nm, respectively. Fourier transform infrared spectroscopy analyses confirmed the encapsulation of IAA or IBA in the chitosan nanoparticles. Meanwhile, the characteristic peaks of IAA or IBA were detected on silver nanoparticles. In-vitro adventitious rooting of microcuttings of Malling Merton 106 (MM 106) was significantly higher both in chitosan and silver nanoparticles loaded with IAA or IBA (91.7%–62.5%) compared to free IAA or IBA applications (50.0%–33.3%), except for 2.0 mg L^–1 IBA (66.7%). However, the application of 2 mg L^–1 IBA and IBA-nChi at all concentrations caused an undesirable large callus development.     

A Novel Nanoparticle Formulation for Sustained Paclitaxel Delivery

Purpose  To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel. Methods  Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). Results  These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC₅₀ of PTX. Conclusion  These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.     

Preparation and pharmacodynamics of low-molecular-weight chitosan nanoparticles containing insulin

Low-molecular-weight chitosan (LMWC) was obtained by enzymatic degradation and ultrafiltration separation. LMWC nanoparticles with LMWC having 20 kDa weight average molecular weight (M_w) were then prepared by solvent evaporation method. The resultant nanoparticles were spherical with a narrow particle size distribution. LMWC nanoparticles loaded with insulin as a model drug were prepared. The average entrapment efficiency of insulin could reach up to 95.54%. The in vitro drug release profiles from the nanoparticles showed an initial burst of release in the first 2 h, followed by zero order release kinetics. In vivo pharmacodynamics of chitosan nanoparticles containing insulin showed that the nanoparticles showed some hypoglycemic activity. Compared with an insulin solution, a relative bioavailability of 0.737 was observed for four times the dosage of insulin in the chitosan nanoparticles after pulmonary administration.