Effect of manufacturing parameters on the characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres prepared by spray-drying

Desai, K. G.,Park, H. J. Taylor & Francis 2006 Journal of microencapsulation Vol.23 No.1

<P>To prepare the sustained release vitamin C carriers, vitamin C was successfully encapsulated in tripolyphosphate (TPP) cross-linked chitosan (TPP-chitosan) microspheres by the spray-drying method at different manufacturing conditions. Manufacturing parameters (inlet temperature, liquid flow rate, chitosan concentration and volume of 1% w/v TPP solution) had a significant influence on the characteristics of thus prepared microspheres. The optimum spray-drying conditions such as inlet temperature, liquid flow rate and compressed air flow rate for the encapsulation of vitamin C in TPP-chitosan microspheres was found to be 170°C, 2 ml min −1 and 10 l min −1 , respectively. The size and yield of the TPP-chitosan microspheres ranged from 3.9–7.3 µm and 54.5–67.5%, respectively. The encapsulation efficiency of TPP-chitosan microspheres ranged from 45.72–68.7% and it decreased with the increasing volume of 1% w/v TPP solution. At the same cross-linking extent, the encapsulation efficiency of TPP-chitosan microspheres increased when the concentration of chitosan was increased from 0.5–1% w/v. Effect of volume of 1% w/v TPP solution on the surface morphology of chitosan microspheres was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). These studies revealed that chitosan solution (250 ml) cross-linked with 15 ml 1% w/v TPP solution produced more porous microspheres than that cross-linked with 5 and 10 ml TPP solution. The release rate of vitamin C from TPP-chitosan microspheres decreased when the concentration of chitosan was increased from 0.5–1.0% w/v. Vitamin C release rate was also modulated by varying the volume of 1% w/v TPP solution. The release rate of vitamin C from TPP-chitosan microspheres decreased with increasing volume (5–15 ml) of 1% w/v TPP solution.</P>

Mechanism of Albumin Release from Alginate and Chitosan Beads Fabricated in Dual Layers

남윤식,배민수,김성원,노인섭,서준교,이강봉,권일근 한국고분자학회 2011 Macromolecular Research Vol.19 No.5

Biocompatible polysaccharides, such as alginate and chitosan are widely used as drug carriers. Microspheres based on the electrostatic interaction between these two polymers have been attractive as a means to deliver protein drugs because the use of organic solvents can be avoided during their preparation. On the other hand, the mechanisms for drug release, such as disintegration of microspheres, are not completely understood. This paper examined the phenomena of disintegration of the core-shell type microspheres consisting of alginate and chitosan. The microspheres formed by either chitosan-coated alginate or alginate-coated chitosan were generated using a labmade instrument consisting of a syringe pump connected to a glass nozzle. Using fluorophore-labeled polysaccharides,the disintegration of each polymer layer from the microspheres was monitored as a function of time. The alginate-coated chitosan microspheres demonstrated enhanced stability with increasing concentration of the chitosan core. The presence of an alginate shell itself also increased the stability of the microsphere compared to the microspheres without an alginate coating. The chitosan concentration, however, did not have any effect on the stability of the chitosan-coated alginate microspheres. The microspheres synthesized with alginate in the core demonstrated concentration-dependent stability. In these microsphere experiments, the microsphere stability was found to be related directly to the protein release kinetics. In the alginate/chitosan-based microspheres, the disintegration property is the primary factor modulating the encapsulated drug release, which suggests the easiest simple method for time-dependent protein drug delivery.

활성산소 방어에 효과적인 천연 항산화 물질을 담지할 수 있는 키토산 마이크로스피어의 제조와 특성

남충현(Choong-Hyun Nam),정경원(Gyeong-Won Jeong),나재운(Jae-Woon Nah) 한국고분자학회 2018 폴리머 Vol.42 No.5

최근 생활 방사선 및 의료 방사선의 심한 노출로 인해 활성산소가 심각하게 유발되고 있으며, 이러한 활성산소를 억제하기 위해 천연 항산화제를 이용한 건강 기능성 식품이 많이 출시되고 있다. 하지만, 천연 항산화제의 자체 사용 시 낮은 생체이용률로 인해 항산화 활성이 반감되는 문제점을 갖고 있다. 본 연구에서는 이러한 천연 항산화제의 생체이용률을 증가시킬 수 있는 키토산 기반의 마이크로스피어 담지체를 개발하고 물리화학적 특성을 분석하여 천연 항산화제 담지체로 응용가능성을 평가하고자 하였다. 기존의 넓은 분자량 분포를 갖는 키토산의 재현성 문제를 해결하기 위해 한외여과막을 이용하여 좁은 분자량 분포와 정확한 분자량 스펙을 갖는 키토산을 제조하였으며, 이를 spray dry 기법을 이용하여 키토산 마이크로스피어를 제조하였다. 분획된 키토산과 마이크로스피어의 물리화학적 특성은 GPC, 1H NMR, FTIR 및 SEM을 이용하여 분석하였고, 이러한 키토산 마이크로스피어의 생체 내에 적용 가능성을 평가하기 위해 세포독성 여부를 MTT assay를 이용하여 확인하였다. 이러한 결과를 통해 키토산 마이크로스피어는 생체 내에 적용이 가능하며, 추후 천연 항산화제를 담지하여 항산화제로 사용했을 시 생체이용률의 증가로 인해 항산화 활성을 극대화할 수 있을 것으로 사료된다. Recently, active oxygen has been seriously induced due to severe exposure to life radiation and medical radiation, and many health functional foods using natural antioxidants have been released to suppress such active oxygen. However, the antioxidant activity of natural antioxidants is reduced due to low bioavailability. In this study, we have developed a chitosan-based microsphere carrier capable of increasing bioavailability of natural antioxidants, and analyzed the physicochemical characteristics of the microsphere carriers to evaluate their applicability as a natural antioxidant carrier. In order to solve the problem of reproducibility of chitosan having a broad molecular weight distribution, chitosan having a narrow molecular weight distribution and accurate molecular weight specification was prepared by using an ultrafiltration membrane. Chitosan microspheres using fractionated chitosan were prepared by spray dry method. The physicochemical properties of the fractionated chitosan and microspheres were analyzed by GPC, 1H NMR, FTIR and SEM. In addition, to evaluate the applicability of chitosan microspheres in vivo, their cytotoxicity was evaluated by MTT assay. These results suggest that chitosan microspheres can be applied in vivo, and natural antioxidant-encapsulated chitosan microsphere can be used to maximize antioxidant activity by increasing bioavailability.

Controlled Release Chitosan Microspheres of Mirtazapine: In Vitro and In Vivo Evaluation

Om Prakash Ranjan,Gopal Venkatesh Shavi,Usha Yogendra Nayak,Karthik Arumugam,Ranjith Kumar Averineni,Pandey Sureshwar,Sreenivasa Reddy Meka 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

The purpose of the study was to formulate and evaluate controlled release chitosan microspheres of mirtazapine (MTZ) to improve the bioavailability by altering the pharmacokinetic profiles of the drug. Chitosan microspheres were prepared to prolong the release of the drug into the systemic circulation. Microspheres were prepared by a single water in oil (w/o) emulsion technique varying the chitosan/drug ratio, stirring speed and concentration of the crosslinking agent (glutaraldehyde). Drug-polymer compatibility studies were carried out using fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The microspheres were evaluated for encapsulation efficiency, particle size, surface morphology, swelling index, in vitro release, as well as erosion and in vivo studies in rats. The FT-IR and DSC studies revealed no interaction between drug and polymer. The encapsulation efficiency of different formulation varied from 53 ± 1.2% to 78 ± 1.5%. The mean particle size of the optimized formulation F-14 was 106.4 ± 0.5 μm. Surface morphology revealed that chitosan microspheres were discrete and spherical in shape with a porous surface. The release of MTZ from chitosan microspheres was rapid up to 4 h, and then it was continuously and slowly released up to 48 h. Optimized formulation (F-14) was found to be stable under accelerated storage conditions based on International Conference on Harmonisation guidelines. Pharmacokinetic studies revealed that the optimized formulation showed significant increases in systemic exposure (AUC = 177.70 ± 7.39 μg·h/mL), half-life (4.72 ± 0.46 h) and reduced clearance (0.009 ± 0.0001 L/h) compared to pure drug administration. Hence, the present study demonstrates that controlled release formulation of MTZ microspheres using chitosan can improve pharmacokinetic profiles of MTZ.

Preparation of Mucoadhesive Chitosan-Poly(acrylic acid) Microspheres by Interpolymer Complexation and Solvent Evaporation Method Ⅰ

Cho, Sang-Min,Choi, Hoo-Kyun 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2

Mucoadhesive microspheres were prepared by interpolymer complexation of chitosan with poly(acrylic acid) (PAA) and solvent evaporation method to increase gastric residence time. The chitosan-PAA complex formation was confirmed by differential scanning calorimetry and swelling study. The DSC thermogram of chitosan-PAA microspheres showed two exothermic peaks for the decomposition of chitosan and PAA. The swelling ratio of the chitosan-PAA micro-spheres was dependent on the pH of the medium. The swelling ratio was higher at pH 2.0 than at neutral pH. The results indicated that the microspheres were formed by electrostatic interaction between the carboxyl groups of PAA and the amine groups of chitosan. The effect of various process parameters on the formation and morphology of microspheres was investigated. The best microspheres were obtained when 1.5% of the high molecular weight chitosan and 0.3% of PAA were used as an internal phase. The optimum internal phase volume was 7%. The corn oil was used as the external phase of emulsion, and span 80 was used as the surfactant. The prepared microspheres had spherical shape.

Preparation of Mucoadhesive Chitosan-Poly(acrylic acid) Microspheres by Interpolymer Complexation andSolvent Evaporation Method I

조상민,최후균 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2

Mucoadhesive microspheres were prepared by interpolymer complexation of chitosan with poly(acrylic acid) (PAA) and solvent evaporation method to increase gastric residence time. The chitosan-PAA complex formation was confirmed by differential scanning calorimetry and swelling study. The DSC thermogram of chitosan-PAA microspheres showed two exothermic peaks for the decomposition of chitosan and PAA. The swelling ratio of the chitosan-PAA microspheres was dependent on the pH of the medium. The swelling ratio was higher at pH 2.0 than at neutral pH. The results indicated that the microspheres were formed by electrostatic interaction between the carboxyl groups of PAA and the amine groups of chitosan. The effect of various process parameters on the formation and morphology of microspheres was investigated. The best microspheres were obtained when 1.5% of the high molecular weight chitosan and 0.3% of PAA were used as an internal phase. The optimum internal phase volume was 7%. The corn oil was used as the external phase of emulsion, and span 80 was used as the surfactant. The prepared microspheres had spherical shape.

Phagocytic Uptake of Surface modified PLGA Microspheres Using Dendritic Cell

( Ji Seon Kim ),( Young Sung Lee ),( Jung Gil Lee ),( Jeong Sook Park ),( Jong Kil Lee ),( Youn Bok Chung ),( Kun Han ) 한국약제학회 2011 Journal of Pharmaceutical Investigation Vol.41 No.3

The purpose of this study was to evaluate the phagocytic uptake of surface modified PLGA microspheres containing ovalbumin (OVA) into dendritic cell. In order to find the most suitable formulation for targeted delivery to antigen presenting cells (APC), OVA was encapsulated by a double emulsion solvent evaporation method with three PLGA microspheres (PLGA 50:50, PLGA 75:25 and PLGA 85:15) and two surface modified microspheres by chitosan and sodium dodecyl sulfate (SDS). Physicochemical properties were evaluated in terms of size, zeta potential, encapsulation efficiency, different scanning calorimeter (DSC), x-ray diffraction, morphology, and OVA release test from microspheres. Phagocytic activity was estimated using dendritic cells and analyzed by fluorescence activated cell sorter (FACS). The result showed that zeta potential of PLGA particles was changed to positive by the chitosan modification. The release profile of chitosan modified PLGA microspheres exhibited sustained release after initial burst. The chitosan modified microspheres had higher phagocytic uptake than the other microspheres. Such physicochemical properties and phagocytic uptake studies lead us to conclude that chitosan modified microspheres is more suitable formulation for the targeted delivery of antigens to APC compared with the other microspheres.

Preparation of Mucoadhesive Chitosan-Poly(acrylic acid) Microspheres by Interpolymer Complexation and Solvent Evaporation Method II

조상민,최호균 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.5

A mucoadhesive microsphere was prepared by an interpolymer complexation and solvent evaporation method, using chitosan and poly(acrylic acid) (PAA), to prolong the gastric residence time of the delivery system. The Fourier transform infrared results showed that microspheres were formed by an electrostatic interaction between the carboxyl groups of the PAA and the amine groups of the chitosan. X-ray diffraction and differential scanning calorimetry analysis showed that the enrofloxacin in the chitosan-PAA microsphere was molecularly dispersed in an amorphous state. Scanning electron microscopy of the surface and the quantity of mucin attached to the microspheres indicated that chitosan-PAA microspheres had a higher affinity for mucin than those of chitosan alone. The swelling and dissolution of the chitosan- PAA microspheres were found to be dependent on the pH of the medium. The rate of enrofloxacin released from the chitosan-PAA microspheres was slower at higher pH; therefore, based on their mucoadhesive properties and morphology, the chitosan-PAA microspheres can be used as a mucoadhesive oral drug delivery system.

Preparation of Mucoadhesive Chitosan-Poly(Acrylic acid) Microspheres by Interpolymer Complexation and Solvent Evaporation Method II

Cho, Sang-Min,Choi, Hoo-Kyun The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.5

A mucoadhesive microsphere was prepared by an interpolymer complexation and solvent evaporation method, using chitosan and poly(acrylic acid) (PAA), to prolong the gastric resid ence time of the delivery system. The Fourier transform infrared results showed that microspheres were formed by an electrostatic interaction between the carboxyl groups of the PAA and the amine groups of the chitosan. X-ray diffraction and differential scanning calorimetry analysis showed that the enrofloxacin in the chitosan-PAA microsphere was molecularly dispersed in an amorphous state. Scanning electron microscopy of the surface and the quantity of mucin attached to the microspheres indicated that chitosan-PAA microspheres had a higher affinity for mucin than those of chitosan alone. The swelling and dissolution of the chitosan-PAA microspheres were found to be dependent on the pH of the medium. The rate of enrofloxacin released from the chitosan-PAA microspheres was slower at higher pH; therefore, based on their mucoadhesive properties and morphology, the chitosan-PAA microspheres can be used as a mucoadhesive oral drug delivery system.

Effect of Drug Loading in Chitosan/PCL Microsphere on fibroblast growth

마진쉬엔,엄혜원,류규환,김경현,이재영,서아인,최선희,이우걸 한국공업화학회 2018 한국공업화학회 연구논문 초록집 Vol.2018 No.0

The efficacy of medical drugs can be strongly affected by the types of drug delivery system. At the same time, drug release from carrier is directly related by the formulation of the drug-loaded carrier. In drug delivery system, organic microspheres are often adopted as drug carrier. Chitosan (CHN) possesses highly positive charges, which can be utilized to immobilize organic drugs via electrostatic interaction and used in medical and pharmaceutical applications. poly(e-caprolactone) (PCL) is biocompatible and degrades under physiological environment. In this study, we prepared microspheres by combining chitosan CHN and PCL. The morphology, surface charge, and chemical state of the comlex microspheres were analyzed using SEM, zeta potential, and FTIR. We also analyzed the drug release kinetics using high perfromance liquid chromatography. Fibroblast proliferation in response to drug release was evaluated.