Applications of polysaccharides in topical and transdermal drug delivery: A recent update of literature

Abstract The main aim of transdermal drug delivery (TDD) is to deliver a specific dose of drug across the skin and to reach systemic circulation at a controlled rate. On the other hand skin is the target for topical drug delivery. Mentioned drug delivery systems (DDS) have numerous advantages compared to oral and parenteral routes. Avoidance of first-pass metabolism, prevent drug degradation due to harsh environment of the stomach, allow controlled drug delivery, provide patient compliance, and pain-free administration are a few of them. To achieve all of them, a DDS with suitable polymer is the primary requisite. Based on the recent trends, natural polymers have been more popular in comparison to synthetic polymers because the former possesses favourable properties including nontoxic, biodegradable, biocompatible, low cost, sustainable and renewable resources. In this context polysaccharides, composed of chains of monosaccharides bound together by glycosidic bonds, have been successfully employed to augment drug delivery into and across the skin with various formulations such as gel, membrane, patches, nanoparticles, nanofibres, nanocomposite, and microneedles. In this chapter, various polysaccharides such as cellulose, chitosan, and their semisynthetic derivatives, alginate, pectin, carrageenan etc, were discussed with their diverse topical and TDD applications. In addition, various formulations based on polysaccharides and limitations of polysaccharides were also briefly discussed.

Polymer nanomedicines for osteosarcoma therapy / 中国组织工程研究

BACKGROUND: In recent years, various polymer nanoparticles have been developed as anticancer drug carriers to prolong blood circulation time and Improve intratumoral accumulation, and then enhance the therapeutic efficacy on osteosarcoma. OBJECTIVE: To review the application and development of polymer nanomedicines for treatment of osteosarcoma based on latest related studies. METHODS: A computer-based online search of Web of Science, NCBI, and PubMed was performed to search publications published between January 1900 and June 2019 with the search terms “osteosarcoma; polymer; nanopartlcle; controlled drug delivery; tumor therapy”. A total of 265 publications were screened out, and 107 of them regarding polymer nanoparticles for treatment of osteosarcoma were included in the final analysis. RESULTS AND CONCLUSION: Osteosarcoma is the most common primary malignant bone tumor, mainly affecting children and adolescents. The long-term survival rate of osteosarcoma patients is low due to early lung metastasis and high local invasiveness. Although chemotherapy increases the survival rates of patients with osteosarcoma, its application potential is limited by severe side effects and drug resistance. Compared with traditional chemotherapy, polymer nanomedicines reduce the toxicity to healthy tissues, prolong the blood circulation time in vivo, and provide continuous release of chemotherapy drugs at the tumor sites, thereby Improving the therapeutic efficacy. Therefore, polymer nanomedicines have great application prospects In the treatment of osteosarcoma because of their unique advantages.

Formulation And Evaluation Of Controlled Release Maintenance Dose Loaded Niosomes Of Anti-Hypertensive Drug

The present study was aimed to formulate, comparatively evaluate and optimize multiple lipid drug carriers of valsartan for oral controlled release to overcome the problems associated with the drug such as bioavailability, to reduce the dosage regimen, half life and to determine the appropriateness of niosomal formulation as a drug carrier. Ether injection method was chosen for the formulation of physically and chemically stable niosomes of valsartan. The formulation and process parameters were optimized by manufacturing placebo niosomes. Than drug loaded niosome was prepared by varying the concentration of span 60. The prepared nine formulations were evaluated for various parameters. Placebo niosomes were evaluated for appearance, odour, texture, creaming volume, pH and changes after 15 days. The medicated nine formulations were evaluated for organoleptic properties (appearance/color, odour), pH, total drug content, entrapment efficiency, mean particle size and polydispersibility index, zeta potential and In-vitro drug release. All formulations were off-white in color, odourless, and fluid in nature. It was stable and did not show sedimentation. The pH was found to be in the range of 4.6-5.4. Drug content was found in the range of 89.13 to 99.52. The Entrapment efficiency was found in range of 79.05 to 98.24. The mean vesicle size of drug loaded niosomes of the different batches ranged between 2.52-3.42μm. The polydispersvity index was in the range of 0.325 to 0.420 which indicates a narrow vesicle size distribution. The values of zeta potential were in the range of -20.29 mV to -30.55 mV which indicates that niosome had sufficient charge and mobility to inhibit aggregation of vesicles. All the nine formulations shows constant drug release in controlled manner up to 24 h. Formulation V7 was considered to be the best formulation as the % drug content (99.52 ± 0.97), % entrapment efficiency (98.24 ± 1.50) and % drug release at the end of 24th h (98.55) were high for V7. The optimized formulation V7 showed higher degree of correlation coefficient (r2) 0.9805 which indicates process of constant drug release from dosage form. The present study concludes that the prepared niosome is a convenient and efficiency carrier for the delivery of antihypertensive drug. Besides this, it provided controlled delivery of drug.

Preparation of Drug Eluting Natural Composite Scaffold Using Response Surface Methodology and Artificial Neural Network Approach

Silk fibroin/xanthan composite was investigated as a suitable biomedical material for controlled drug delivery, and blending ratios of silk fibroin and xanthan were optimized by response surface methodology (RSM) and artificial neural network (ANN) approach. A non-linear ANN model was developed to predict the effect of blending ratios, percentage swelling and porosity of composite material on cumulative percentage release. The efficiency of RSM was assessed against ANN and it was found that ANN is better in optimizing and modeling studies for the fabrication of the composite material. In-vitro release studies of the loaded drug chloramphenicol showed that the optimum composite scaffold was able to minimize burst release of drug and was followed by controlled release for 5 days. Mechanistic study of release revealed that the drug release process is diffusion controlled. Moreover, during tissue engineering application, investigation of release pattern of incorporated bioactive agent is beneficial to predict, control and monitor cellular response of growing tissues. This work also presented a novel insight into usage of various drug release model to predict material properties. Based on the goodness of fit of the model, Korsmeyer–Peppas was found to agree well with experimental drug release profile, which indicated that the fabricated material has swellable nature. The chloramphenicol (CHL) loaded scaffold showed better efficacy against gram positive and gram negative bacteria. CHL loaded SFX55 (50:50) scaffold shows promising biocomposite for drug delivery and tissue engineering applications.

Floating ability and drug release evaluation of gastroretentive microparticles system containing metronidazole obtained by spray drying

Abstract Gastroretentive floating microparticles were developed and evaluated for the controlled metronidazole delivery for treatment of gastric disease. Floating microparticles, varying in proportions of chitosan and hydroxypropyl methylcellulose or ethylcellulose, were obtained by spray drying. Floating microparticles were characterized by physicochemical and in vitro studies, according to their floating ability and drug delivery. Microparticles presented mean diameter from 1.05 to 2.20 µm. The infrared spectroscopy confirmed the drug encapsulation and showed no chemical linkage between microparticles components. X-ray diffraction showed changes in the drug`s solid state, from crystalline to amorphous, indicating partial drug encapsulation, due to the presence of some crystalline peaks of metronidazole in microparticles. All microparticles floated immediately in contact of simulated gastric fluid and both floating and drug release profiles were dependent of microparticles composition. Microparticles samples constituted by chitosan and hydroxypropyl methylcellulose revealed the best relationship between floating duration and drug release, remaining floating during the occurrence of the drug release, ideal condition for the floating gastroretentive systems.

Development of Ultrasound Sensitive eLiposomes Containing Doxorubicin for Drug Delivery.

Aims: A novel nanocarrier was formulated by remote loading of doxorubicin (Dox) into a dipalmitoylphosphatidylcholine (DPPC) liposome that also contains various perfluorocarbon (PFC) droplets within its aqueous interior. It was shown that Dox can be loaded to a level of up to 67% into these large unilamellar vesicles composed of DPPC and cholesterol by employing a transmembrane pH gradient technique. Methods: The different encapsulation efficiencies for these eLipoDox constructs of differing PFC composition are 45.5% (PFC5), 31.5% (PFC6) and 66.7% (PFC5/PFC6 mixture, PFCm). At 30 seconds of insonation, the eLipoDox formulation with PFCm droplets appeared to release more Dox than did eLipoDox with pure PFC5 or PFC6 droplets. The thermal stability of these eLipoDox formulations were examined at 37°C at different times; then controlled delivery was demonstrated by applying low-frequency ultrasound (US) at 1 W/cm2. Results: The eLipoDox with PFC6 or PFCm showed the best combination of thermal stability and drug release. An immunoblotting analysis indicates that ultrasound-triggered Dox release from eLipoDox could provide a higher quantity of nanodrug into tumor cells and thus may have cytostatic effects in cancer cells. Conclusion: These eLipoDox constructs with low boiling point PFCs have the potential to provide more effective ultrasonically activated drug therapy to a desired location.

In vitro Bioluminescence Used as a Method for Real-Time Inhibition Zone Testing for Antibiotic- Releasing Composites.

Aims: This study describes the potential of real-time bioluminescence imaging in evaluating the antibiotic efficiency of two cylinder-shaped bioabsorbable antibiotic-releasing composites by in vitro inhibition zone tests. The bacterial infections of bone tissue can cause extensive hard and soft tissue damage and decrease the efficiency of oral antibiotic therapy due to the poor blood circulation in the infected area. To overcome this problem, new, locally antibiotic-releasing biodegradable composites have been developed. Study Design & Methodology: The two composites evaluated in this study were composed of poly(L-lactide-co-ε-caprolactone) matrix, β-tricalcium phosphate ceramic and either ciprofloxacin or rifampicin antibiotic. The composites were tested with genetically modified model pathogens of osteomyelitis (Pseudomonas aeruginosa and Staphylococcus epidermidis) in vitro in inhibition zone tests using a method of real-time bioluminescence. Results: The first signs of the effect of the released ciprofloxacin or rifampicin became visible after four hours of incubation and were seen as changed bioluminescence around the composite pellet on a culture dish. Both of the composite types showed excellent effects against the sensor bacteria within the diffusion area. Bioluminescence measurements suggested that no survivor bacteria capable of evolving resistant strains were left inside the inhibition zones. The S. epidermidis bacterial strain was an inhibition sensor and P. aeruginosa was a stress sensor. Conclusion: These results highlight the potential of the composite materials against the pathogens of osteomyelitis. The approach allows continuous visual inspection of the efficacy of the antibiotics against the bacteria

Magnetic and Compartmental Targeting of Azathioprine using Gelatin Microspheres: Formulation, Physicochemical Characterization and In Vitro Release Studies.

Azathioprine loaded gelatin microspheres were formulated to control/target drug release in an arthritic joint by magnetic force or intra-articular injection. Glutaraldehyde cross linked microspheres were characterized for drug loading, entrapment efficiency, gas chromatography, magnetite content, particle size, scanning electron microscopy (SEM), Fourier-Infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and in vitro release studies. The gelatin microspheres loaded with azathioprine showed 17% of drug loading with 82% of entrapment efficiency. Gelatin magnetic microspheres showed 13% of loading with 87% of entrapment efficiency. Gas chromatography confirms absence of residual glutaraldehyde in the microspheres. The magnetite content of the azathioprine loaded gelatin magnetic microsphere was 25.7% w/w. The average particle sizes of gelatin nonmagnetic and magnetic microspheres were 41 and 54 μm, respectively. SEM confirms the spherical nature of the microspheres. FT-IR revealed the absence of drug polymer interaction, and DSC suggested amorphous nature of entrapped drug in the microspheres. The formulated microspheres could release the drug over a period of 48 h.

Novel vesicular system: An overview.

Novel drug delivery attempts to either sustain drug action at a predetermined rate, or by maintaining a relatively constant, effective drug level in the body with concomitant minimization of undesirable side effects. The vesicular systems are highly ordered assemblies of one or several concentric lipid bilayer formed, when certain amphiphillic building blocks are confronted with water. The vesicular system such as liposomes, niosomes, sphingosomes, ethosomes, transferosomes and pharmacosomes are used to improve the therapeutic index of both existing and new drug molecules by encapsulating an active medicament inside vesicular structure in one such system. It prolongs the existence of the drug in systemic circulation and finally reduces the toxicity. Such different systems are widely used in gene delivery, tumor targeting, oral formulations, in stability and permeability problems of drugs. Now a days vesicle as a carrier system have become the vehicle of choice in drug delivery and lipid vesicles were found to be of value in immunology, membrane biology and diagnostic technique and most recently in genetic engineering.

Studies on the controlled drug delivery system of thermosensitive chitosan-based hydrogel containing doxorubicin in vitro / 中国海洋药物

Objective To study the preparation of temperature-sensitive hydrogel system,which is based on chitosan added by ?-glycerophosphate and is used to deliver the doxorubicin,and its delivery property.Methods The doxorubicin-containing temperature-sensitive hydrogel system based on chitosan was prepared;ultraviolet spectrophotometry was used to measure the content of doxorubicin;the drug release by the sustained release system was observed in vitro.Results Doxorubicin-containing temperature-sensitive hydrogel system based on chitosan was prepared and the release curve was obtained to express its delivery property.Conclusion The temperature-sensitive system based on chitosan can be used to deliver doxorubicin.The results provided the experimental basis for improvement of the delivery of doxorubicin.