A simple and robust method for pre-wetting poly (lactic-co-glycolic) acid microspheres
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractPoly (lactic-co-glycolic) acid microspheres are amenable to a number of biomedical procedures that support delivery of cells, drugs, peptides or genes. Hydrophilisation or wetting of poly (lactic-co-glycolic) acid are an important pre-requisites for attachment of cells and can be achieved via exposure to plasma oxygen or nitrogen, surface hydrolysis with NaOH or chloric acid, immersion in ethanol and water, or prolonged incubation in phosphate buffered saline or cell culture medium. The aim of this study is to develop a simple method for wetting poly (lactic-co-glycolic) acid microspheres for cell delivery applications. A one-step ethanol immersion process that involved addition of serum-supplemented medium and ethanol to PLGA microspheres over 30 min–24 h is described in the present study. This protocol presents a more efficient methodology than conventional two-step wetting procedures. Attachment of human skeletal myoblasts to poly (lactic-co-glycolic) acid microspheres was dependent on extent of wetting, changes in surface topography mediated by ethanol pre-wetting and serum protein adsorption. Ethanol, at 70% (v/v) and 100%, facilitated similar levels of wetting. Wetting with 35% (v/v) ethanol was only achieved after 24 h. Pre-wetting (over 3 h) with 70% (v/v) ethanol allowed significantly greater (p ≤ 0.01) serum protein adsorption to microspheres than wetting with 35% (v/v) ethanol. On serum protein-loaded microspheres, greater numbers of myoblasts attached to constructs wetted with 70% ethanol than those partially wetted with 35% (v/v) ethanol. Microspheres treated with 70% (v/v) ethanol presented a more rugose surface than those treated with 35% (v/v) ethanol, indicating that more efficient myoblast adhesion to the former may be at least partially attributed to differences in surface structure. We conclude that our novel protocol for pre-wetting poly (lactic-co-glycolic) acid microspheres that incorporates biochemical and structural features into this biomaterial can facilitate myoblast delivery for use in clinical settings.
CitationWright, B., Parmar, N., Bozec, L., Aguayo, S. D. and Day, R. M. (2015) A simple and robust method for pre-wetting poly (lactic-co-glycolic) acid microspheres, Journal of Biomaterials Applications, 30(2), pp. 147-159.
JournalJournal of Biomaterials Applications
SponsorsThis project was supported by grants from the UK Medical Research Council (MR/L002752/1) and Sir Halley Stewart Trust. The research was undertaken at UCL/UCLH which receives funding from the Department of Health’s NIHR as a Comprehensive Biomedical Research Centre.
Showing items related by title, author, creator and subject.
Towards a More Desirable Dry Powder Inhaler Formulation: Large Spray-Dried Mannitol Microspheres Outperform Small MicrospheresKaialy, Waseem; Hussain, Tariq; Alhalaweh, Amjad; Nokhodchi, Ali (2013-08-06)Purpose To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer®) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid–state formbut different sizes. Methods Spray dried mannitol (SDM) particles were characterized in terms of size, surface area, morphology, water content, solid–state, density and electrostatic charge by a novel approach. DPI formulations composed of SDM and albuterol sulphate (AS) were prepared and evaluated in terms of drug content homogeneity and in vitro aerosolization performance. Results All SDM particles generated similar fine particle fractions of AS. Formulations consisting of larger SDM particles demonstrated better drug content homogeneity, reduced amounts of drug loss and reduced oropharyngeal deposition. Comparing different SDM products demonstrated that SDM powders with relatively poorer flowability, wider size distributions and higher charge density generated DPI formulations with poorer drug content homogeneity and deposited higher amount of drug on the inhaler, mouthpiece adaptor and throat. DPI formulation total desirability increased linearly with the mean diameter of SDM. Conclusion Particle shape and solid–state form of mannitol could dominate over carrier size, bulk density, flowability and charge in terms of determining the aerosolization behaviour of AS formulated with mannitol carrier, at least within the experimental protocols applied in the present study.
Bionic cartilage acellular matrix microspheres as scaffold for engineering cartilageLiu, Jun; Yu, Cheng; Lu, Gonggong; Tang, James Zhenggui; Wang, Yonghui; Zhang, Boqing; Sun, Yong; Lin, Hai; Wang, Qiguang; Liang, Jie; et al. (Royal Society of Chemistry, 2018-12-12)Extracellular matrix (ECM) scaffolds made from decellularized natural cartilage have been successfully used in cartilage lesion repair, but allogeneic cartilage donors are always in shortage and xenogeneic cartilage tissues may have the risk of unknown disease transfer. In this study, we constructed artificial bionic cartilage microspheres by encapsulating MSCs in collagen microspheres and cultured in a chondrogenic-inducing medium. Then, acellular matrix microsphere (BCAMM) scaffolds were fabricated from the cultured microspheres at three different developmental stages. A novel technique was introduced to fabricate BCAMM scaffolds, which enabled the production and utilization of the scaffolds in a short time. Due to the differences in surface morphologies and biological compositions, the three BCAMM scaffolds showed different chondrogenic effects. The 10-day BCAMM (10-BCAMM) scaffold showed the best overall results, successfully inducing MSC chondrogenesis without any additional fetal bovine serum or induction components (TGF-β or dexamethasone). In comparison, the 5-day BCAMM (5-BCAMM) scaffold showed potential osteogenic effects. The advantages of micron-sized BCAMMs are outlined, specifically in the easier decellularization process without grinding, homogeneous cell seeding and infiltration, chondrogenic induction and better fitting to the irregular lesion shape.
The Encapsulation and Release of Flutamide Using Poly (ε-Caprolactone) MicrospheresChaggar, Sanjit (2016-08-01)In 2012 prostate cancer contributed towards 8% (1.1 million cases) of all cancer incidences around the world. This type of cancer is prevalent in men between the ages of 65-79 years old, with 25% of all cases occurring in men younger than 65 years old. Treatments that are currently available for prostate cancer include surgery, hormone therapy, radiation therapy and chemotherapy. These treatment methods are either very invasive or have harsh side effects including diarrhoea, nausea, alter liver function, anaemia and fatigue. A wide range of anti-cancer drugs in use today have very poor physiochemical properties. New knowledge in this area is required to develop an advanced drug delivery system that improves the properties of these drugs. An example is anti-androgenic drugs such as flutamide (FLT) used in hormonal therapy. The disadvantages to FLT are that it has low bioavailability in oral formulations, low aqueous solubility, compliance issues and rapid first pass metabolism. Recent advances in novel drug delivery have led to the formation of controlled release delivery systems using non-toxic polymeric microspheres. These polymeric microspheres encapsulate the active agent improving its bioavailability and compliance, reducing drug toxicity and side effects. The aim of this investigation was to develop a controlled release FLT delivery system in the form of poly (ε-caprolactone) (PCL) microspheres. The study was set out to evaluate the microspheres aesthetics, physicochemical properties and drug release behaviour. A central composite experimental design was employed to evaluate the effect of two process variables, (1) the polymer PCL at three different molecular weights (MW) 80kDa, 65kDa and 10kDa, (2) the surfactant (poly(vinyl alcohol) (PVA) at two molecular weight ranges 13-23kDa and 30-70kDa. Preparing the organic phase consisted of 500mg of PCL and 50mg of FLT being completed dissolved in 10mL chloroform. The inorganic phase was formed by dissolving PVA in deionised water at a 0.5% weight/volume solution. The organic phase was added drop wise into the inorganic phase to create a 1.30 oil/water ratio. The emulsion was homogenised at 5000rpm for 1 minute. The chloroform was rotary evaporated off, followed by centrifugation and being frozen for 24 hours. The scanning electron microscopy (SEM) analysis was carried out with a freeze dried sample of the microspheres. The percentage yield was calculated to see how the sample amount changed with two process variables. Using laser diffraction, the average diameter of microspheres was determined. The percentage encapsulation efficiency (%EE) was carried out by dissolving PCL-FLT microspheres in Sanjit S. Chaggar 1004138 Masters of Philosophy v | P a g e chloroform and ethanol. The solution was centrifuged and the UV-absorbance was recorded at 300nm. The in-vitro drug release was analysed via dissolution, PCL-FLT microspheres were suspended in a dialysis bag and stirred at 100rpm, in a phosphate buffer saline (PBS) solution. The SEM data suggested the PCL 80kDa/ PVA 30-70kDa formulation produced the smoothest and most uniform microspheres with the highest mean percentage encapsulation efficiency at 90.92% ±1.08%. The micrographs showed that as the PCL MW increased from 10kDa to 80kDa the particle size increased from 5.5μm to 8.4μm. Regarding percentage yield the 80kDa/ PVA 13-23kDa FLT loaded formulations produced the most amount of product, averaging at 72.95% ±1.28%. However, after statistical analysis of %EE and product yield there was no significant difference in data between the two MW ranges of PVA (P>0.05). Dissolution results showed PCL 80kDa/ PVA 30-70kDa microspheres to have a maximal release of 80.23% over 16 days with an intial burst release of 15.38% within the first 4 hours of dissolution. This suggested that encapsulted FLT microspheres can be administered less frequently (once every 2 weeks) at a lower dose (50mg), as the release rate (80.23%/ 16 days) of encapsulted FLT is slower than the half life of free FLT (8 hours). Overall the formulation that produced the most ideal microspheres regarding aesthetics, size, yield, encapsulation efficiency and dissolution was the PCL 80kDa/ PVA 30-70kDa formulation. Further studies that can be conducted include transition electron microscopy (TEM) analysis to evaluate the internal components of the PCL-FLT microsphere complex. A co-polymer such as poly(lactic-co-glycolic acid) (PLGA) can be incorparated along side PCL in order to further improve the encapsulation efficiency. Toxicity studies can also be carried out involving prostate cancer cell lines (MTT Assay).