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Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior.

ABSTRACT: The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system. In this study, two kind of aqueous model drugs with different molecule weight, Congo red and albumin from bovine serum (BSA) were nano-encapsulated in poly (dl-lactic-co-glycolic acid) (PLGA) microspheres by emulsion electrospray. In the preparation process, the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution. The emulsion was then electrosprayed to fabricate drug-nanoencapsulated PLGA microspheres. The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase (V_w/V_o ) and the molecule weight of model drugs. Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to V_w/V_o . With the increase of the volume ratio of aqueous drug phase, the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate. Moreover, BSA showed a slower release rate from PLGA microspheres comparing to Congo red, which indicated the drug release rate could be affected by not only V_w/V_o but also the molecule weight of model drug. In brief, the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple system to achieve controlled drug release at a desired rate satisfying the need of the practices.

SUBMITTER: Yao S

PROVIDER: S-EPMC5043157 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior.

Yao Shenglian S Liu Huiying H Yu Shukui S Li Yuanyuan Y Wang Xiumei X Wang Luning L

Regenerative biomaterials 20160921 5

The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system. In this study, two kind of aqueous model drugs with different molecule weight, Congo red and albumin from bovine serum (BSA) were nano-encapsulated in poly (dl-lactic-co-glycolic acid) (PLGA) microspheres by emulsion electrospray. In the preparation p ...[more]

PMID: 27699061

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Project description:Vaccines are a critical clinical tool in preventing illness and death due to infectious diseases and are regularly administered to children and adults across the globe. In order to obtain full protection from many vaccines, an individual needs to receive multiple doses over the course of months. However, vaccine administration in developing countries is limited by the difficulty in consistently delivering a second or third dose, and some vaccines, including the inactivated polio vaccine (IPV), must be injected more than once for efficacy. In addition, IPV does not remain stable over time at elevated temperatures, such as those it would encounter over time in the body if it were to be injected as a single-administration vaccine. In this manuscript, we describe microspheres composed of poly(lactic-co-glycolic acid) (PLGA) that can encapsulate IPV along with stabilizing excipients and release immunogenic IPV over the course of several weeks. Additionally, pH-sensitive, cationic dopants such as Eudragit E polymer caused clinically relevant amounts of stable IPV release upon degradation of the PLGA matrix. Specifically, IPV was released in two separate bursts, mimicking the delivery of two boluses approximately one month apart. In one of our top formulations, 1.4, 1.1, and 1.2 doses of the IPV serotype 1, 2, and 3, respectively, were released within the first few days from 50mg of particles. During the delayed, second burst, 0.5, 0.8, and 0.6 doses of each serotype, respectively, were released; thus, 50mg of these particles released approximately two clinical doses spaced a month apart. Immunization of rats with the leading microsphere formulation showed more robust and long-lasting humoral immune response compared to a single bolus injection and was statistically non-inferior from two bolus injections spaced 1 month apart. By minimizing the number of administrations of a vaccine, such as IPV, this technology can serve as a tool to aid in the eradication of polio and other infectious diseases for the improvement of global health.

Project description:Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Although existing techniques for producing polymeric drug carriers offer the possibility of achieving greater production yield across a wide range of sizes, these methods are improbable to precisely tune particle size while upholding uniformity of particle size and morphology, ensuring consistent production yield, maintaining batch-to-batch reproducibility, and improving drug loading capacity. Herein, we developed a novel scalable method for the synthesis of tunable-sized microparticles with improved monodispersity and batch-to-batch reproducibility via the coaxial flow-phase separation technique. The study evaluated the effect of various process parameters on microparticle size and polydispersity, including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution, whereas surfactant concentration had the most substantial impact on the morphology of particles. In addition to synthesizing microparticles of spherical morphology yielding particle sizes in the range of 5-50 µm across different formulations, we were able to also synthesize several microparticles exhibiting different morphologies and particle concentrations as a demonstration of the tunability and scalability of this method. Notably, by adjusting key determining process parameters, it was possible to achieve microparticle sizes in a comparable range (5-7 µm) for different formulations despite varying the concentration of polymer and volume of polymer solution in the organic phase by an order of magnitude. Finally, by the incorporation of fluorescent dyes as model hydrophilic and hydrophobic drugs, we further demonstrated how polymer amount influences drug loading capacity, encapsulation efficiency, and release kinetics of these microparticles of comparable sizes. Our study provides a framework for fabricating both hydrophobic and hydrophilic drug-loaded microparticles and elucidates the interplay between fabrication parameters and the physicochemical properties of microparticles, thereby offering an itinerary for expanding the applicability of this method for producing polymeric microparticles with desirable characteristics for specific drug delivery applications.

Dataset Information

Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior.

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Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior.

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