Injectable Delivery System Research Articles

Thermally Triggered Injectable Hydrogel Carrier System for Mesenchymal Stem Cell Delivery to Promote Intervertebral Disc Regeneration

Introduction Instability of the motion segment as a result of intervertebral disc (IVD) degeneration is well known as a major cause of low back pain. Several tissue engineering and stem cell approaches have been investigated to attempt to regenerate the degenerate IVD. However, many of the proposed therapies would entail lengthy/risky operations to “implant” the tissue regeneration scaffold. Our vision is to develop a novel, injectable biomaterial delivery system which can deliver mesenchymal stem cells (MSCs) to the degenerate nucleus pulposus (NP) to stimulate regeneration, together with inhibitors of degeneration if required and provide mechanical support to the motion segment enabling regeneration to take place. Materials and Methods Here, we investigated a novel hydrogel system, which can be maintained as a liquid ex vivo and can be injected into the IVD where body temperature triggers in situ solidification. Human MSCs were incorporated into hydrogel systems and cell viability, migration characteristics, SEM, gene expression for NP markers, and matrix production investigated to determine differentiation capacity of incorporated MSCs. Mechanical properties of hydrogel systems were determined using dynamic mechanical analysis and compared with native NP tissue. Microparticles incorporation to provide delivery of inhibitors of degeneration were also investigated. Results Viability of MSCs was maintained within hydrogel systems for the 6 weeks investigated, where they were shown to migrate through the hydrogel system, deposit matrix within and differentiate toward NP cells with a switch in matrix gene expression from collagen type I to type II, and deposition of GAGs with immunopositivity seen for aggrecan following 4 weeks in culture. DMA analysis demonstrated hydrogel systems containing 10% hyaluronic acid displayed similar mechanical properties to native NP cells. Hydrogel systems were injected via 26-gauge needles into collagenase digested bovine caudal discs, which was maintained during loading of the bovine motion segments. In addition, microparticles were successfully incorporated into hydrogel systems in the liquid state before thermal triggered solidification. Conclusion Here, we have developed a hydrogel system with the potential to deliver MSCs via minimally invasive injection using small bore needles which decreases the chance of inducing damage to the annulus fibrosus. Hydrogel systems were nontoxic, support MSC growth and differentiation, and show potential to provide mechanical support to the motion segment while regeneration takes place. Such a therapy combined with inhibition of degeneration could show great promise for early and mid-stages of degeneration. Disclosure of Interest None declared

An overview of Regenerative Pulp Therapy in Children

A remarkable shift in paradigm is seen with the treatment of pulp therapy procedures from conventional to regenerative ones since 10-15 years in the field of pediatric endodontics. Though conventional treatment techniques provide excellent success for many conditions, an ideal form of therapy might consist of regenerative approaches in which diseased or necrotic pulp tissues are removed and replaced with healthy pulp tissue. Regenerative pulp procedure is the creation and delivery of tissues to replace diseased, missing, and traumatized pulp. This review provides an overview on the biology of dental pulp tissue and regenerative pulp procedures like stem cells therapy, scaffolds, injectable delivery systems, pulp implantation, gene therapy, revascularization and tissue engineering including their goals and describe possible techniques that will allow this to become a reality.

Alumina particle reinforced TiO2 composite films grown by direct liquid injection MOCVD

The use of a liquid injection delivery system to form composite films containing nanoparticles was investigated. Al2O3–TiO2 films were grown on silicon substrates by direct liquid injection MOCVD (DLI-MOCVD) at 400 °C. The α-Al2O3 nanoparticles (α-Al2O3NPs) dispersed in TiO2 films resulted from co-deposition using colloidal α-Al2O3 solution and titanium tetraisopropoxide as titanium precursor. Scanning electron microscopy coupled with EDS as well as Raman spectroscopy confirmed the presence of α-Al2O3NPs aggregates embedded in the TiO2 matrix. The liquid injection system coupled with CVD technique can be promising to form composite films containing preformed nanoparticles.

Shear Reversible Cell/Microsphere Aggregate as an Injectable for Tissue Regeneration

Injectable delivery systems have been widely used in tissue engineering as they can deliver cells into the body in a minimally invasive manner. In this study, it is hypothesized that microspheres with a similar size of cells could effectively form a shear reversible aggregate in the presence of cells and the aggregate could be useful to engineer tissues. Alginate microspheres are prepared by an emulsion method, followed by modification with a peptide containing the arginine-glycine-aspartic acid (RGD) sequence. RGD-modified alginate microspheres form an aggregate in the presence of chondrocytes, and the aggregation behavior is shear reversible. This cell/microsphere aggregate is useful to deliver chondrocytes into an animal model using a syringe, and effectively regenerates cartilage tissues in vivo.

Nanotechnology applications in osteodistraction

Most current strategies for bone regeneration have relatively satisfactory results. However, there are drawbacks and limitations associated with their use and availability, and even controversial reports about their efficacy and cost-effectiveness. The induction of new bone formation through distraction osteogenesis (DO) is widespread clinical application in the treatment of bone defects, limb deformities, and fracture nonunions. However, a lengthy period of external fixation is usually needed to allow the new bone to consolidate, and complications such as refracture at the distraction gap often occur. Although various biomaterials have been used as injectable delivery systems in DO models, little has been reported on the use of nanobiomaterials as carrier materials for the sustained release of growth factors in bone regeneration. One area of focus in nanotechnology is the delivery of osteogenic factors in an attempt to modulate the formation of bone. This review article seeks to demonstrate the potential of nanobiomaterials to improve biological applications pertinent to osteodistraction.

Vaccine and Needle-Free Vaccination Delivery System

Needle-free injection delivery system is a new method use a unique profile to deliver vaccine to the proper tissue depth for injection. The shift from needle-based to needle-free immunization is also catalyzed, in part, by the realization that skin, which can increase vaccine immunogenicity, is ideal target for vaccine delivery. As a promising delivery of vaccines system, it has the potential to decrease the dose of vaccine antigen, enhance immune response and may furthermore help to reduce costs.

New Gadgets in Local Anesthesia: A review

Local pain management is the most critical aspect of patient care in dentistry. When efforts to achieve local anesthesia are unsuccessful, the resulting stress for both the patient and practitioner can be significant. It is imperative on our part to update our knowledge and skills in using newer alternatives in pain control and management and ways of administering them to increase the comfort level of our patients and resolve the cliched paradigm of Pain and Dentistry are inseparable. The improvements in techniques for local anesthesia are probably the most significant advances that have occurred in dental science. This paper provides an update on comparatively newer gadgets that are less commonly used to deliver local anesthetics. Keywords: Computer controlled local anesthesia delivery system (CCLAD), Intraosseous Injection delivery system, Local anesthesia delivery device, Needle-less injector, Vibrating tactile devices.

Effects of Cell Density and Biomacromolecule Addition on the Flow Behavior of Concentrated Mesenchymal Cell Suspensions

With the rapidly growing interest in the use of mesenchymal stromal cells (MSCs) for cell therapy and regenerative medicine applications, either alone as an injected suspension, or dispersed within injectable hydrogel delivery systems, greater understanding of the structure-function-property characteristics of suspensions of adhesion-dependent mesenchymal cells is required. In this paper, we present the results of an experimental study into the flow behavior of concentrated suspensions of living cells of mesenchymal origin (fibroblasts) over a wide range of cell concentrations, with and without the addition of hyaluronic acid (HA), a commonly utilized biomolecule in injectable hydrogel formulations. We characterize the change in the shear viscosity as a function of shear stress and shear rate for cell volume fractions varying from 20 to 60%. We show that high volume fraction suspensions of living mesenchymal cells, known to be capable of homotypic interactions, exhibit highly complex but reproducible rheological footprints, including yield stress, shear thinning and shear-induced fracture behaviors. We show that with the addition of HA, we can significantly modify and tailor the rheology of these cell suspensions at all volume fractions. Using FACS and confocal imaging, we show that the observed effect of HA addition is due to a significantly modulation in the formation of cellular aggregates in these suspensions, and thus the resultant volume spanning network. Considering the aggregates as fractal structures, we show that by taking into account the changes in volume fractions with shear, we are able to plot a master curve for the range of conditions investigated and extract from it the average adhesion force between individual cells, across a population of millions of cells. The outcomes of this study not only provide new insight into the complexity of the flow behaviors of concentrated, adhesive mesenchymal cell suspensions, and their sensitivity to associative biomacromolecule addition, but also a novel, rapid method by which to measure the average adhesion force between individual cells, and the impacts of biomacromolecules on this important parameter.

Corelease of Bioactive VEGF and HGF from Viscous Liquid Poly(5-ethylene ketal ε-caprolactone-co-d,l-lactide)

The potential of a viscous liquid injectable delivery system composed of poly(5-ethylene ketal ε-caprolactone-co-D,L-lactide) (PEKCDLLA) to release bioactive vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) using an osmotic pressure release mechanism for the purpose of treating critical limb ischemia was investigated. VEGF and HGF were lyophilized separately with trehalose and bovine serum albumin (BSA) and incorporated into the polymer by simple mixing. VEGF and HGF were released by convective flow through superhydrated regions formed within the polymer as a result of the osmotic activity generated upon dissolution of the particles, along with the contributions of polymer degradation at later time points. A sustained release of highly bioactive VEGF and HGF for over 40 days with minimal burst was achieved under conditions of multidirectional delivery. The solubility of the growth factors in the concentrated trehalose solution formed upon dissolution of the particle within the polymer was determined to be a key parameter governing the rate and extent of growth factor release. This formulation approach, of using a low viscosity polymer delivery vehicle, is potentially useful for localized delivery of acid and temperature sensitive proteins, such as VEGF and HGF. This system may also serve as a platform for controlled and predictable delivery patterns for other therapeutic proteins in other clinical settings.

Current research of diabetic macular edema

Diabetic macular edema (DME) is a leading cause of vision loss in diabetic patients.It is very important to correctly select a treating approach for DME.At present,the treating methods of DME include retinal laser photocoagulation,application of the glucocorticoid,intravitreous injection of anti-vascular endothelial growth factor (VEGF) drugs,administration of inhibitor of protein kinase C,vitrectomy and combined treatment etc.However,each method has its advantage and disadvantage.Retinal photocoagulation,vitrectomy,intravitreous injection and drug delivery system implantation are invasive treatment methods,and they can not rescue damaged retinal photoreceptors.Therefore,it is recommended that DME should be early diagnosed and effective treatment.The research status at home and abroad and future development trends of DME treatment were summarized. Key words: Diabetic mellitus/complication, macular edema; Retina; Photocoagulation; Controlled release system; Vitrectomy

Biodegradable in situ gel-forming controlled vancomycin delivery system based on a thermosensitive mPEG-PLCPPA hydrogel

In this study, a biodegradable in situ gel-forming controlled drug delivery system based on a thermosensitive methoxy polyethylene glycol-co-poly (lactic acid-co-aromatic anhydride) (mPEG-PLCPPA) hydrogel was studied. The hydrogels were formed by micelle aggregation with rising temperature. The hydrogels underwent a temperature-dependent sol–gel–sol transition, which was a flowing sol at ambient temperature and a non-flowing gel at the physiological body temperature. The residual weight and pH value changes after degradation and the viscosity properties of the hydrogel were investigated. The in vitro release behavior of vancomycin from the mPEG-PLCPPA hydrogels at different concentrations was also investigated. The results showed that the mPEG-PLCPPA amphiphilic copolymer could self-assemble to form micelles at low concentrations, and that the particle sizes gradually increased with increasing temperature. The hydrogel maintained a stable degradation rate and provided a moderate pH microenvironment after degradation for 30 days. Vancomycin sustained a stable release profile from the hydrogel over a 10-day period. Furthermore, good biocompatibility was proven by MTT assay and live and dead test. Therefore, the mPEG-PLCPPA hydrogel shows promise as an injectable local antibiotic delivery system.

Sulforaphane–PLGA microspheres for the intra-articular treatment of osteoarthritis

Sulforaphane (SFN) is a member of the isothiocyanate family that has anti-inflammatory action as well as anti-carcinogenic properties. The authors have devised an intra-articular injectable SFN–PLGA microsphere system that can be used for treating osteoarthritis (OA). The purpose of this study was to evaluate the in vitro and in vivo efficacy of the SFN–PLGA microsphere system. Articular chondrocytes were obtained from knee OA patients and were cultured in monolayers. The optimal concentration of SFN was obtained and the dose of SFN–PLGA microspheres was determined based on the concentration. The in vitro anti-inflammatory effect on markers such as cyclooxygenase (COX)-2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, and matrix metalloproteinase (MMP)-2 was assessed by real-time PCR and Western blotting. The in vivo therapeutic effect of SFN–PLGA microspheres was investigated using surgically-induced rat OA model. Treatment with SFN–PLGA microspheres inhibited the mRNA and protein expression of COX-2, ADAMTS-5 and MMP-2 induced by LPS in articular chondrocytes. Intraarticular SFN–PLGA microspheres delayed the progression of surgically-induced osteoarthritis in rats. In conclusion, SFN–PLGA microspheres can be a useful injectable delivery system for treating osteoarthritis.

Growth factor delivery from hydrogel particle aggregates to promote tubular regeneration after acute kidney injury

Local delivery of growth factors (GFs) can accelerate regeneration of injured tissue, but for many medical applications, injectable GF delivery systems are required for clinical success. Viscoelastic, injectable aggregates of micrometer-sized hydrogel particles made of multiarmed polyethylene glycol (starPEG) and heparin were prepared and tested for site-specific paracrine stimulation of tissue regeneration. Heparin was used as it binds, protects and releases numerous GFs. Hydrogel based delivery of basic fibroblast growth factor (bFGF) and murine epidermal growth factor (EGF) was monitored utilizing enzyme-linked immunosorbent assay (ELISA). bFGF was released slowly because of its high affinity to the heparin while the significantly higher release of the non-specific binding EGF was controlled by diffusion only. To investigate GF delivery in vivo, a hydrogel loaded with murine EGF or bFGF was injected subcapsularly into the left kidney of mice with experimental acute kidney injury caused by glycerol induced rhabdomyolysis. Visual examination confirmed sustained stability of the injected gel aggregates during the timescale of the experiment. The number of proliferating kidney tubular epithelial cells was quantified both in the injected kidney and the non-injected contralateral kidney. bFGF delivery from hydrogels induced a significant increase in cell proliferation in the injected kidney, although small effects were also seen in the non-injected kidney due to a systemic effect. EGF delivery strongly increased cell proliferation for both kidneys, but also showed a local effect on the injected kidney. The hydrogel without loaded GFs was used as a control and showed no increase in cell proliferation. Our results suggest that this novel starPEG-heparin hydrogel system can be an effective approach to deliver GFs locally.

Versatile tuning of supramolecular hydrogels through metal complexation of oxidation-resistant catechol-inspired ligands

The mussel byssal cuticle employs DOPA-Fe3+ complexation to provide strong, yet reversible crosslinking. Synthetic constructs employing this design motif based on catechol units are plagued by oxidation-driven degradation of the catechol units and the requirement for highly alkaline pH conditions leading to decreased performance and loss of supramolecular properties. Herein, a platform based on a 4-arm poly(ethylene glycol) hydrogel system is used to explore the utility of DOPA analogues such as the parent catechol and derivatives, 4-nitrocatechol (nCat) and 3-hydroxy-4-pyridinonone (HOPO), as structural crosslinking agents upon complexation with metal ions. HOPO moieties are found to hold particular promise, as robust gelation with Fe3+ occurs at physiological pH and is found to be largely resistant to oxidative degradation. Gelation is also shown to be triggered by other biorelevant metal ions such as Al3+, Ga3+ and Cu2+ which allows for tuning of the release and dissolution profiles with potential application as injectable delivery systems.

Tracking injectable microspheres in dynamic tissues with encapsulated superparamagnetic iron oxide nanoparticles.

Trackable spheres of similar size to those typically used for sustained protein delivery are prepared by incorporating superparamagnetic iron oxide (SPIO) nanoparticles into the core of poly(lactide-co-glycolide) microspheres. The visibility of injections in static and temporally in dynamic tissue systems is demonstrated. This method improves upon other, less sensitive imaging modalities in their ability to track injectable delivery systems. The results obtained confirm the localization of microspheres to the injected target area and highlight the novelty of tracking delivery vehicles for other applications.

Biodegradable donepezil lipospheres for depot injection: optimization and in-vivo evaluation

The purpose of this study was to develop an injectable depot liposphere delivery system with high loading capacity for controlled delivery of donepezil to decrease dosing frequency and increase patient compliance. A 3(2) full factorial design was employed to study the effect of lipid type and drug-to-lipid ratio on the yield, encapsulation efficiency, mean diameter and the time required for 50% drug release (t(50%) ). The pharmacokinetic behaviour of the lipospheres in rabbits was studied using tandem mass spectrometry. The yields of preparations were in the range of 66.22-90.90%, with high encapsulation efficiencies (89.68-97.55%) and mean particle size of 20.68-35.94 µm. Both lipid type and drug-to-lipid ratio significantly affected t(50%) (P<0.0001), where the lipids can be arranged: glyceryl tripalmitate>compritol>cetyl alcohol, and the drug-to-lipid ratios can be arranged: 1:40>1:20>1:10. The flow time of lipospheres through 19-gauge syringe needle was less than 6s indicating good syringeability. The mean residence time of the subcutaneous and intramuscular lipospheres was significantly higher than the solution (almost 20 fold increase), with values of 11.04, 11.34 and 0.53 days, respectively (P<0.01). Subcutaneous and intramuscular delivery of donepezil glyceryl tripalmitate lipospheres achieves depot release, allowing less frequent dosing.

Synthesis, characterization, drug-loading capacity and safety of novel pH-independent amphiphilic amino acid copolymer micelles.

A novel block copolymer containing two polymeric components, poly(L-aspartic acid)-b-poly (L-phenylalanine) (PAA-PPA), was synthesized and its potential for the preparation of copolymer micelles with a poorly water-soluble drug was investigated in this study. The chemical structure and physical properties of PAA-PPA were characterized by FTIR, 1H NMR and TG. The degree of polymerization of PAA-PPA was calculated by analyzing the relative area of N-CH signal and C-CH3 of 1H NMR spectra. The critical micelle concentration (CMC) of the PAA-PPA achieved a minimum of 11.1 mg/L. Studies on the drug-free PAA-PPA solutions showed PAA-PPA aggregation into micellar type in the sub-150 nm size range. Furthermore, the size of the PAA-PPA micelles was found to be pH-independent between the pH range of 4.0 and 8.0, which could be favorable to avoid the limitation of the size change at the specified pH value seeking drug stability. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was studied as a poorly water-soluble model drug. The drug-loading and entrapment efficiency of the ATPR-loaded PAA-PPA micelles were 30.9 wt% and 87.9 %, respectively. The high drug-loading and entrapment efficiency were due to the synergistic effect of the micellar encapsulation and the binding interaction between drug and PAA-PPA. The ATPR-loaded PAA-PPA micelles showed a narrow size distribution, low zeta potential, high drug-loading capacity and good stable. The PAA-PPA was safer than Tween-80 and Cremophor EL (CrmEL) as an injectable pharmaceutical adjuvant for ATPR as indicated by the hemolysis and cytotoxicity studies. The novel amphiphilic amino acid copolymer can be considered as a prospective injectable delivery system for ATPR in terms of the pH-independent, greater drug-loading capacity and safety.

Injectable Hydrogel for Mesenchymal Stem Cell and Protein Delivery to the Degenerate Intervertebral Disk

IntroductionInstability of the motion segment as a result of intervertebral disk degeneration is well known as a major cause of lower back pain. In recent years, a number of tissue engineering and stem cell approaches have been investigated in an attempt to regenerate the degenerate IVD. However, many of the proposed therapies would entail lengthy/risky operations to “implant” the tissue regeneration scaffold. Our vision is to develop a novel, injectable biomaterial delivery system which will deliver mesenchymal stem cells (MSCs) to the degenerate nucleus pulposus (NP) to stimulate regeneration, it will also deliver inhibitors of degeneration, while providing mechanical support to the motion segment during this process. Here, we investigate a novel hydrogel system, which can be maintained as a liquid ex vivo and can potentially be injected into the IVD where it will gel in situ. Materials and MethodsHuman MSCs were labelled with a green fluorescent membrane dye to enable visualization before culture within or on hydrogel systems. Effects on cell viability, migration characteristics, matrix production, and differentiation capacity of MSCs were investigated. Additionally, the feasibility of injection through narrow bore needles, into a model degenerate IVDs using collagenase digested bovine caudal disks, was investigated. In addition, effects of the degenerate tissue niche were investigated on MSC behavior to determine whether inhibitors of degeneration would need to be codelivered. MSC were treated with IL-1beta and induction of matrix degrading enzymes and expression of IL-1 family genes investigated. ResultsViability of MSCs were unaffected by coculture with hydrogel systems, or following growth on or in such systems over time periods of up to 6 weeks. MSCs adhered to the hydrogel systems and were shown to migrate through the system when applied to the upper surface of a preset hydrogel system. Additionally, MSCs mixed with liquid hydrogel before setting and maintained at 37°C for up to 4 weeks, survived, proliferated, synthesized collagen type II and aggrecan matrix (Fig. 1) similar to that seen within the NP including aggrecan, gene expression analysis demonstrated expression of key genes. Liquid hydrogel was successfully injected into degenerated bovine disks where it fill both the large voids and the smaller branches induced by collagenase digestion. MSC treated with IL-1 induced expression of IL-1, IL-1Ra, MMP3 and MMP13 were also upregulated. IL-Ra was successfully incorporated into the hydrogel system. ConclusionWe have developed a hydrogel system with the potential to deliver MSCs via minimally invasive injection via narrow bore needles, decreasing the risk of damage to the annulus fibrosus. The system is nontoxic, supports MSC growth, differentiation and shows potential to provide mechanical support to the motion segment while regeneration takes place. Such a therapy combined with inhibition of degeneration shows immense potential for early and midstages of spinal degeneration.I confirm having declared any potential conflict of interest for all authors listed on this abstractYesDisclosure of InterestNone declared

Injectable Hydrogel for Mesenchymal Stem Cell and Protein Delivery to the Degenerate Intervertebral Disk

Introduction Instability of the motion segment as a result of intervertebral disk degeneration is well known as a major cause of lower back pain. In recent years, a number of tissue engineering and stem cell approaches have been investigated in an attempt to regenerate the degenerate IVD. However, many of the proposed therapies would entail lengthy/risky operations to “implant” the tissue regeneration scaffold. Our vision is to develop a novel, injectable biomaterial delivery system which will deliver mesenchymal stem cells (MSCs) to the degenerate nucleus pulposus (NP) to stimulate regeneration, it will also deliver inhibitors of degeneration, while providing mechanical support to the motion segment during this process. Here, we investigate a novel hydrogel system, which can be maintained as a liquid ex vivo and can potentially be injected into the IVD where it will gel in situ. Materials and Methods Human MSCs were labelled with a green fluorescent membrane dye to enable visualization before culture within or on hydrogel systems. Effects on cell viability, migration characteristics, matrix production, and differentiation capacity of MSCs were investigated. Additionally, the feasibility of injection through narrow bore needles, into a model degenerate IVDs using collagenase digested bovine caudal disks, was investigated. In addition, effects of the degenerate tissue niche were investigated on MSC behavior to determine whether inhibitors of degeneration would need to be codelivered. MSC were treated with IL-1beta and induction of matrix degrading enzymes and expression of IL-1 family genes investigated. Results Viability of MSCs were unaffected by coculture with hydrogel systems, or following growth on or in such systems over time periods of up to 6 weeks. MSCs adhered to the hydrogel systems and were shown to migrate through the system when applied to the upper surface of a preset hydrogel system. Additionally, MSCs mixed with liquid hydrogel before setting and maintained at 37°C for up to 4 weeks, survived, proliferated, synthesized collagen type II and aggrecan matrix (Fig. 1) similar to that seen within the NP including aggrecan, gene expression analysis demonstrated expression of key genes. Liquid hydrogel was successfully injected into degenerated bovine disks where it fill both the large voids and the smaller branches induced by collagenase digestion. MSC treated with IL-1 induced expression of IL-1, IL-1Ra, MMP3 and MMP13 were also upregulated. IL-Ra was successfully incorporated into the hydrogel system. Conclusion We have developed a hydrogel system with the potential to deliver MSCs via minimally invasive injection via narrow bore needles, decreasing the risk of damage to the annulus fibrosus. The system is nontoxic, supports MSC growth, differentiation and shows potential to provide mechanical support to the motion segment while regeneration takes place. Such a therapy combined with inhibition of degeneration shows immense potential for early and midstages of spinal degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared

Co-encapsulation and sustained-release of four components in ginkgo terpenes from injectable PELGE nanoparticles

It is difficult to develop injectable sustained delivery systems for herbal medicines because of their composition complexity. Encapsulating various compounds with different physiochemical properties and achieving their synchronized and sustained release seem too hard to realize. In this paper, an injectable nanoparticulate system based on an mPEG–PLGA–mPEG (PELGE) platform was prepared for co-encapsulation and sustained release of four active components (ginkgolides A, B, C and bilobalide) in Ginkgo biloba extract. Different carriers were screened by macrophage uptake experiment for their ability to be long-circulation. Drug loaded nanoparticles were prepared with 10% PEG2000 modified PLGA by a co-precipitation method. The encapsulation efficiency of the total ginkgo terpenes (GT) in the optimal formulation was 78.84±2.06% with a loading dose of 11.90±0.31mg/150mg PELGE. The particles exhibited a spherical shape with a mean diameter of 123.3±44.0nm and zeta potential of −30.86±2.49mV. Sustained and synchronized release of the four components from PELGE nanoparticles was observed both in vitro and in vivo, which was mainly contributed to the long circulation of PEGylated nanoparticles and the slow degradation of PLGA. The half-life time of the four terpenoid compounds were also significantly improved by incorporation into PELGE nanoparticles. The results indicate that a PELGE nanoparticle is a promising carrier system for sustained and synchronized release of herbal medicines containing multiple components.