Biodegradable progesterone microsphere delivery system for osteoporosis therapy

The purpose of this study was to formulate and characterize a controlled-release biodegradable delivery system of progesterone for the treatment or prevention of osteoporosis. Microspheres of progesterone were formulated using copolymers of poly(glycolic acid-co-dl-lactic acid)(PGLA 50/50 and PGLA 15/85) and poly(L-lactic acid)(L-PLA) of similar molecular weight by the emulsion solvent evaporation technique. The effects of process variables, such as volume fraction, polyvinyl alcohol (PVA) concentration, polymer composition, and stir speed during preparation, on the yield, encapsulation efficiency (EEF), particle size distribution, in vitro release profiles of progesterone, and surface morphology of progesterone microspheres were investigated. Increasing the volume fraction from 9% to 22% increased the EEF without significantly increasing the yield; however, the rate of progesterone release from the microspheres decreased. Increasing the PVA concentration from 1% to 5% had no significant influence on the EEF, but the rate of progesterone release from microspheres increased. Polymer composition had no significant effect on the EEF, but had a significant effect on the particle size distribution, surface morphology, and release rate of progesterone from the microspheres. Stir speed did not have a significant influence on the EEF; however, stir speed influenced particle size distribution and the rate of progesterone release from microspheres of the same sieve-size range. The results suggest that controlled release of progesterone is possible by varying the different process variables, and that PGLA 50/50 provided the slowest release of progesterone. This should provide a means of delivering progesterone for months for the treatment or prevention of osteoporosis in postmenopausal women.     

Biodegradable microparticulates of beta-estradiol: preparation and in vitro characterization

Beta-estradiol has been recommended for the long-term therapy of osteoporosis and its oral formulations are subjected to intensive first pass metabolism. The present investigation was aimed at preparing and characterizing biodegradable microparticles of beta-estradiol with polymers such as PLA, PLGA 85/15, PLGA 75/25, and their mixtures. The microparticles were prepared by solvent evaporation method using methylene chloride as a solvent and polyvinyl alcohol as a surfactant. The drug-polymer ratios were 1:3, 1:5, and 1:7. The prepared microparticles (twelve formulations) were tested for encapsulation efficiency and in vitro drug release in 50% methyl alcohol/phosphate buffer pH 7.4. The results showed that the encapsulation efficiency varied from 81 to 100% and the formulation fabricated from PLGA 85/15 (1:3) showed less burst and consistent long time release. This formulation when further characterized displayed irregular spherical shape with an average particle size of 72 µm. The crystallinity of the drug was reduced when investigated using X-ray diffractometry. No chemical interaction between the drug and the polymer was observed as evidenced by FT-IR analysis. The results indicated that beta-estradiol biodegradable microparticles with PLGA 85/15 (1:3) could be a suitable approach for long term therapy of osteoporosis.     

Development of an Implantable,Biodegradable, Controlled Drug Delivery System for Local Antibiotic Therapy

Abstract

A novel drug delivery system was developed using a monoglyceride (Glycerol Monostearate) and a water-soluble release rate modifier as the matrix. Cefuroxime sodium (Zinacef®) was chosen as a model drug in this study. Formulations (cylindrical implants 6 × 6 mm) were prepared by a melt-dispersion method. Dissolution studies were performed using USP paddle method. The effect of glycerol, PEG 400 and their combination on drug release profiles was studied. Two assay methods (UV and HPLC) for cefuroxime analysis were compared. Percent recovery from four formulations (A-D) was higher with UV than HPLC assay. While both UV and HPLC assay methods were developed for cefuroxime, only HPLC assay is stability indicating. Glycerol showed higher accelerating effect than PEG 400 on the drug release. All formulations exhibited extended release of cefuroxime. Degradation of cefuroxime occurred mainly during dissolution suggesting drug stability in the formulations.     

Biodegradable Microparticulates of Beta-Estradiol: Preparation and In Vitro Characterization

ABSTRACT

Beta-estradiol has been recommended for the long-term therapy of osteoporosis and its oral formulations are subjected to intensive first pass metabolism. The present investigation was aimed at preparing and characterizing biodegradable microparticles of beta-estradiol with polymers such as PLA, PLGA 85/15, PLGA 75/25, and their mixtures. The microparticles were prepared by solvent evaporation method using methylene chloride as a solvent and polyvinyl alcohol as a surfactant. The drug-polymer ratios were 1:3, 1:5, and 1:7. The prepared microparticles (twelve formulations) were tested for encapsulation efficiency and in vitro drug release in 50% methyl alcohol/phosphate buffer pH 7.4. The results showed that the encapsulation efficiency varied from 81 to 100% and the formulation fabricated from PLGA 85/15 (1:3) showed less burst and consistent long time release. This formulation when further characterized displayed irregular spherical shape with an average particle size of 72 µm. The crystallinity of the drug was reduced when investigated using X-ray diffractometry. No chemical interaction between the drug and the polymer was observed as evidenced by FT-IR analysis. The results indicated that beta-estradiol biodegradable microparticles with PLGA 85/15 (1:3) could be a suitable approach for long term therapy of osteoporosis.     

In Vitro and In Vivo Release of Naltrexone from Biodegradable Depot Systems

ABSTRACT

The aim of this study was to prepare poly(d, l-lactide) (PLA) microspheres containing naltrexone (NTX) by a solvent evaporation method, and to evaluate both in vitro and in vivo release characteristics and histopathological findings of tissue surrounding an implant formulation in rats.

This method enabled the preparation of microspheres of regular shape and relatively narrow particle size distribution. The in vitro release profiles of NTX from PLA microspheres showed the release of NTX did not follow zero-order kinetics. An initial burst release was observed, subsequently followed by a nearly constant rate of 0.4% per day after ten days. The cumulative amount of NTX released at the end of 60 days was 80%. Compressed microspheres showed near zero-order sustained release of NTX for 360 days. The plasma NTX levels in rats showed that for compressed microspheres NTX concentrations were constant and exceeded 2 ng/mL for 28 days. Throughout the 28 days of study, the implantations cause a minor inflammatory response, which can be regarded as a normal defence mechanism. The sustained release performance of NTX from the biodegradable depot systems may provide a reliable, convenient, and safe mechanism for the administration of NTX for the long-term treatment of opioid dependence.     

Biodegradable Materials for Bone Repairs:A Review

With attractive research and development of biomaterials,more and more opportunities have been brought to the treatments of human tissue repairs.The implant is usually no need to exist in the body accompanied with the recovery or regeneration of the tissue lesions,and the long-term effect of exotic substance to human body should be reduced as lower as possible.For this purpose,biodegradable materials,including polymers, magnesium alloys and ceramics,have attracted much attention for medical applications due to their biodegradable characters in body environment.This paper in turn introduces these three different types of widely studied biodegradable materials as well as their advantages as implants in applications for bone repairs.Relevant history and research progresses are summarized.     

生物可降解聚乳酸骨科材料研究进展

在骨外科中，聚乳酸中已成为十分重要的生物可降解高分子材料，用作为固定器材，骨诱生支撑体和药物控制缓释材料，本文树其研究进展作了综合评述，对存在问题也进行了一些讨论。     

Facile method for fabricating titania spheres for chromatographic packing

Titania (TiO₂) spheres were fabricated by a solvent evaporation process in which anhydrous ethanol was used as the only solvent. This is a simple and novel route for the fabrication of TiO₂ spheres. The spheres have a narrow particle size distribution and an average diameter of approximately 1.0 µm. The crystal structure of the prepared spheres was improved by high-temperature processing. A possible mechanism for the formation and growth of the spheres is proposed in which titanic acid molecules react with each other through hydroxyl condensation to form primary TiO₂ particles. These aggregate and increase in size by surface reaction, and finally form spheres.     

明胶微球/磷酸镁基骨水泥复合药物缓释体系的构建

采用乳化交联法制备出粒径主要分布在100~300 μm的载药明胶微球, 分析了交联剂含量、药物含量和转速对载药率和包封率的影响及药物含量和转速对微球粒径的影响。对载药明胶微球与磷酸镁基骨水泥进行复合, 探讨微球降解过程中复合体系孔隙率的变化及其在体外药物释放的规律, 以期获得一种具有药物缓释性能的多孔磷酸镁基复合骨水泥。结果表明, 随着葡萄糖浓度增加, 载药率和包封率先上升再下降; 随着药物含量的增加, 载药率保持上升, 包封率先上升后下降; 随着转速增加, 载药率和包封率均下降。综合分析, 在转速为400 r/min、葡萄糖浓度为0.5 g/mL、药物与明胶质量比为1:2的条件下制备的载药明胶微球载药量较高, 且粒径合适。将复合不同比例该载药微球的磷酸镁基骨水泥浸泡在Tris-HCl缓冲溶液中进行体外药物释放研究, 结果表明: 在释放前期(0~10 h)药物释放速率较快, 之后药物释放明显减缓。7 d后, 微球几乎降解完全, 药物释放率达到60%~89%, 达到了一定的药物缓释效果。     

可生物降解高分子微针的制作及透皮应用

透皮给药相比于传统的给药方式,具有更多的优势．但是,皮肤的角质层能够阻止外源性物质的侵犯,限制了透皮给药系统的应用．为此,基于微针的透皮给药系统的提出增大了透皮给药系统的应用范围．首先,采用MEM技术制作单晶硅微针．接下来,提出一种新颖、简单而且经济的方法快速制作聚乳酸微针．通过理论分析及有限元分析微针的力学性能,表明微针有足够的强度．体外透皮实验表明,未经微针处理的皮肤,钙黄绿素10h的累计渗透量只有0．17±0．07 μg／cm2;手动进针处理的皮肤只达到4．54±1．17 μg／cm2,比未用微针处理的皮肤增加了30倍;经过进针器处理的皮肤,各个时间点的渗透量均有显著性提高（P〈0．05）,渗透量达到45．37±5．80 μg／cm2,比未用微针处理的皮肤增加了300倍．所有的结果都表明,本实验室制备可降解的聚乳酸微针的方法新颖、快速且经济,而且对于透皮给药系统来说具有很大的潜在价值．     

Challenges and Solutions for the Additive Manufacturing of Biodegradable Magnesium Implants

Due to their capability of fabricating geometrically complex structures, additive manufacturing (AM) techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys, which exhibit appropriate mechanical properties and outstanding biocompatibility. However, many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants, such as the difficulty of Mg powder preparation, powder splash, and crack formation during the AM process. In the present work, the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed. A novel Mg-based alloy (Mg–Nd–Zn–Zr alloy, JDBM) powder with a smooth surface and good roundness was first synthesized successfully, and the AM parameters for Mg-based alloys were optimized. Based on the optimized parameters, porous JDBM scaffolds with three different architectures (biomimetic, diamond, and gyroid) were then fabricated by selective laser melting (SLM), and their mechanical properties and degradation behavior were evaluated. Finally, the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate (DCPD) coating treatment, which greatly suppressed the degradation rate and increased the cytocompatibility, indicating a promising prospect for clinical application as bone tissue engineering scaffolds.     

Processing conditions for the production of polystyrene microcapsules containing demineralized water

Microencapsulation has been important for engineering, biology, medicine, and several other fields of science. Microencapsulation is an effective way to protect the encapsulated material (e.g. an aqueous solution or pharmaceutical drug) and control its release to the external environment. Microcapsules are also used for producing anticorrosion systems and, in this case, studies about polymeric microcapsules containing acid solutions are relevant. In this paper, polystyrene microcapsules containing demineralized water were produced. The influence of the core-to-shell ratio, evaporation temperature, and the presence of sodium chloride and a surfactant on the yield of the microencapsulation process was evaluated. Microcapsules were characterized by scanning electron microscopy (SEM), and thermogravimetry that revealed the morphology and thermal behavior of microcapsules in response to changing core-to-shell ratios. SEM images showed mononuclear microcapsules with smooth surfaces. The results indicated that a core-to-shell ratio of 2:1 showed the best encapsulation performance under the conditions of this study. An increase in yield of about 38% was achieved by reducing the evaporation temperature. In addition, the yields obtained in this research are considerably higher than those found in literature.     

Biodegradable Microalgae‐Based Carriers for Targeted Delivery and Imaging‐Guided Therapy toward Lung Metastasis of Breast Cancer

High delivery efficiency, prolonged drug release, and low systemic toxicity are effective weapons for drug delivery systems to win the battle against metastatic breast cancer. Herein, it is shown that Spirulina platensis (S. platensis) can be used as natural carriers to construct a drug‐loaded system for targeted delivery and fluorescence imaging‐guided chemotherapy on lung metastasis of breast cancer. The chemotherapeutic doxorubicin (DOX) is loaded into S. platensis (SP) via only one facile step to fabricate the DOX‐loaded SP (SP@DOX), which exhibits ultrahigh drug loading efficiency and PH‐responsive drug sustained release. The rich chlorophyll endows SP@DOX excellent fluorescence imaging capability for noninvasive tracking and real‐time monitoring in vivo. Moreover, the micrometer‐sized and spiral‐shaped SP carriers enable the as‐prepared SP@DOX to passively target the lungs and result in a significantly enhanced therapeutic efficacy on lung metastasis of 4T1 breast cancer. Finally, the undelivered carriers can be biodegraded through renal clearance without notable toxicity. The SP@DOX described here presents a novel biohybrid strategy for targeted drug delivery and effective treatment on cancer metastasis.     

Stimulus-Responsive Drug Delivery Nanoplatforms for Osteoarthritis Therapy

Osteoarthritis (OA) is one of the most prevalent age-related degenerative diseases. With an increasingly aging global population, greater numbers of OA patients are providing clear economic and societal burdens. Surgical and pharmacological treatments are the most common and conventional therapeutic strategies for OA, but often fall considerably short of desired or optimal outcomes. With the development of stimulus-responsive nanoplatforms has come the potential for improved therapeutic strategies for OA. Enhanced control, longer retention time, higher loading rates, and increased sensitivity are among the potential benefits. This review summarizes the advanced application of stimulus-responsive drug delivery nanoplatforms for OA, categorized by either those that depend on endogenous stimulus (reactive oxygen species, pH, enzyme, and temperature), or those that depend on exogenous stimulus (near-infrared ray, ultrasound, magnetic fields). The opportunities, restrictions, and limitations related to these various drug delivery systems, or their combinations, are discussed in areas such as multi-functionality, image guidance, and multi-stimulus response. The remaining constraints and potential solutions that are represented by the clinical application of stimulus-responsive drug delivery nanoplatforms are finally summarized.     

Development and In Vitro Characterization of Chitosan-based Microspheres for Nasal Delivery of Promethazine

ABSTRACT

Conventional and composed promethazine-loaded microspheres were prepared by spray drying of chitosan solution systems and double water-in-oil-in-water (W/O/W) emulsion systems, respectively. Double emulsions were prepared in two different feed concentrations, with chitosan dissolved in both water phases, and ethylcellulose dissolved in oil phase. Swelling and bioadhesive properties of the microspheres depended on the chitosan content, type and the feed concentration of spray-dried system. Results obtained suggested that better ethylcellulose microcapsules with promethazine in the chitosan matrix were formed when less concentrated emulsion systems were spray-dried. Thus, in case of such a system, with ethylcellulose/chitosan weight ratio of 1:2, prolonged promethazine release was obtained.     

Systemic Delivery of Monoclonal Antibodies to the Central Nervous System for Brain Tumor Therapy

As an essential component of immunotherapy, monoclonal antibodies (mAbs) have emerged as a class of powerful therapeutics for treatment of a broad range of diseases. For central nervous system (CNS) diseases, however, the efficacy remains limited due to their inability to enter the CNS. A platform technology is reported here that enables effective delivery of mAbs to the CNS for brain tumor therapy. This is achieved by encapsulating the mAbs within nanocapsules that contain choline and acetylcholine analogues; such analogues facilitate the penetration of the nanocapsules through the brain–blood barrier and the delivery of mAbs to tumor sites. This platform technology uncages the therapeutic power of mAbs for various CNS diseases that remain poorly treated.     

Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell‐mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer‐specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP‐PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti‐BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP‐PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP‐PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell–cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The “self‐powered” immune cell‐mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.