Biodegradable Polymer Microparticles Research Articles

Preparation of Metformin Biodegradable Polymeric Microparticles by O/O Emulsion Solvent Evaporation: A 32 Full Factorial Design Approach

Background: Sustained release of synthetic polymeric microparticles has gained more attention as drug delivery carriers because of their properties such as good stability, low toxicity, dosing frequency, and simple and mild preparation method. The present work was envisaged to reduce the dosing frequency by preparing drug loaded biodegradable microspheres by the O/O emulsion solvent evaporation technique. Objective: The objective behind microspheres’ preparation is to sustain the metformin release by using ethyl cellulose as a synthetic polymer. The model drug metformin having a low biological half-life (1.5-3 hours) is selected. Methods: As the metformin is highly water soluble in nature, the oil-in-oil solvent evaporation techniques are used and span 80 is utilized as surfactant. The effect of stirring rate and surfactant concentration on the characteristics of encapsulation efficiency and drug release from the microsphere are investigated. Results: The results show that the drug-polymer (1:1) ratio gives better sustained release results. The obtained microparticles are characterized by X-RD analysis and Fe-SEM, and release behavior is checked for release patterns. A 32 full factorial design is employed for the responses. The free-flowing spherical microspheres show high drug entrapment efficiency. Conclusion: The data obtained suggest that microspheres can be successfully designed with sustained release for diabetic treatment.

A review on recent advantages and evaluation of microparticles and their applications

Microparticles are free spherical dust between 1 and 1000 microns made of synthetic, non-biodegradable, and non-biodegradable polymers. There are two types of microparticles: microcapsules and micro matrix. The main types of microparticles are magnetic microparticles, polymer microparticles, bio-adhesive microparticles, biodegradable polymer microparticles, synthetic polymer microparticles, floating microparticles, and radioactive microparticles. The advantage of microcarriers over nanoparticles is that they do not cross the 100 nm interstitium during lymphatic transport and therefore act locally. Toxic substances can be solidified in the form of micro-encapsulated and dried particles. Moreover, methods to characterize numerous physicochemical parameters like drug release, thermal properties, and particle size are introduced, along with new tests like in vitro leaching tests and floating tests.

Chitin nanofiber-coated biodegradable polymer microparticles via one-pot aqueous process

Tailoring the surface of biodegradable microparticles is important for various applications in the fields of cosmetics, biotechnology, and drug delivery. Chitin nanofibers (ChNFs) are one of the promising materials for surface tailoring owing to its functionality, such as biocompatibility and antibiotic properties. Here, we show biodegradable polymer microparticles densely coated with ChNFs. Cellulose acetate (CA) was used as the core material in this study, and ChNF coating was successfully carried out via a one-pot aqueous process. The average particle size of the ChNF-coated CA microparticles was approximately 6 μm, and the coating procedure had little effect on the size or shape of the original CA microparticles. The ChNF-coated CA microparticles comprised 0.2–0.4 wt% of the thin surface ChNF layers. Owing to the surface cationic ChNFs, the ζ-potential value of the ChNF-coated microparticles was +27.4 mV. The surface ChNF layer efficiently adsorbed anionic dye molecules, and repeatable adsorption/desorption behavior was exhibited owing to the coating stability of the surface ChNFs. The ChNF coating in this study was a facile aqueous process and was applicable to CA-based materials of various sizes and shapes. This versatility will open new possibilities for future biodegradable polymer materials that satisfy the increasing demand for sustainable development.

Microparticles entrapping pneumococcal protein SP0845 show improved immunogenicity and temperature stability

Protein based vaccines are the most safe and affordable strategy to combat pneumococcal disease circumventing the limitations of conventional polysaccharide-based vaccines like serotype dependence, high cost and inability to be administered to immunocompromised. SP0845 is a highly conserved vaccine candidate shown to provide protection against heterologous strains of Streptococcus pneumoniae, the primal cause of pneumonia. However, the associated poor immunogenicity warrants the need for adjuvants and multiple doses to mount desired responses. The present study relates to improve the immunogenicity of pneumococcal protein SP0845 by use of poly lactic acid biodegradable polymer microparticles. The immunization studies showed that microparticles elicited higher antibody response compared to alum adjuvanted protein and this immunopotentiation was achieved without the use of any additional adjuvant. They were also capable of eliciting secondary antibody response upon boosting after four months. Further, the particles upon storage at 25 and 37 °C for one month were still capable of mounting an immune response equivalent to those stored in cold chain. Thus, using microparticles entrapping SP0845 for immunization not only improve the immunogenicity but also offer better temperature stability. This can greatly reduce the cost and increase access of protein-based vaccine to resource limited settings.

Polysaccharides as Stabilizers for Polymeric Microcarriers Fabrication.

Biodegradable polymeric microparticles are widely used in drug delivery systems with prolonged-release profiles and/or cell microcarriers. Their fabrication via the oil/water emulsion solvent evaporation technique has normally required emulsifiers in the aqueous phase. The present work aims to evaluate the effectiveness of various polysaccharides, such as chitosan, hyaluronic acid, cellulose, arabinogalactan, guar and their derivatives, as an alternative to synthetic surfactants for polylactide microparticle stabilization during their fabrication. Targeted modification of the biopolymer’s chemical structure was also tested as a tool to enhance polysaccharides’ emulsifying ability. The transformation of biomacromolecules into a form of nanoparticle via bottom-up or top-down methods and their subsequent application for microparticle fabrication via the Pickering emulsion solvent evaporation technique was useful as a one-step approach towards the preparation of core/shell microparticles. The effect of polysaccharides’ chemical structure and the form of their application on the polylactide microparticles’ total yield, size distribution and morphology was evaluated. The application of polysaccharides has great potential in terms of the development of green chemistry and the biocompatibility of the formed microparticles, which is especially important in biomedicine application.

Large fuzzy biodegradable polyester microspheres with dopamine deposition enhance cell adhesion and bone regeneration in vivo

The biodegradable polymer microparticles with different surface morphology and chemical compositions may influence significantly the behaviors of cells, and thereby further the performance of tissue regeneration in vivo. In this study, multi-stage hierarchical textures of poly(D,L-lactic-co-glycolide) (PLGA)/PLGA-b-PEG (poly(ethylene glycol)) microspheres with a diameter as large as 50–100 μm are fabricated based on interfacial instability of an emulsion. The obtained fuzzy structures on the microspheres are sensitive to annealing, which are changed gradually to a smooth one after treatment at 37 °C for 6 d or 80 °C for 1 h. The surface microstructures that are chemically dominated by PEG can be stabilized against annealing by dopamine deposition. By the combination use of annealing and dopamine deposition, a series of microspheres with robust surface topologies are facilely prepared. The fuzzy microstructures and dopamine deposition show a synergetic role to enhance cell-material interaction, leading to a larger number of adherent bone marrow-derived mesenchymal stem cells (BMSCs), A549 and MC 3T3 cells. The fuzzy microspheres with dopamine deposition can significantly promote bone regeneration 12 w post surgery in vivo, as revealed by micro-CT, histological, western blotting and RT-PCR analyses.

Recombinant Filamentous Bacteriophages Encapsulated in Biodegradable Polymeric Microparticles for Stimulation of Innate and Adaptive Immune Responses.

Escherichia coli filamentous bacteriophages (M13, f1, or fd) have attracted tremendous attention from vaccinologists as a promising immunogenic carrier and vaccine delivery vehicle with vast possible applications in the development of vaccines. The use of fd bacteriophage as an antigen delivery system is based on a modification of bacteriophage display technology. In particular, it is designed to express multiple copies of exogenous peptides (or polypeptides) covalently linked to viral capsid proteins. This study for the first time proposes the use of microparticles (MPs) made of poly (lactic-co-glycolic acid) (PLGA) to encapsulate fd bacteriophage. Bacteriophage–PLGA MPs were synthesized by a water in oil in water (w1/o/w2) emulsion technique, and their morphological properties were analyzed by confocal and scanning electron microscopy (SEM). Moreover, phage integrity, encapsulation efficiency, and release were investigated. Using recombinant bacteriophages expressing the ovalbumin (OVA) antigenic determinant, we demonstrated the immunogenicity of the encapsulated bacteriophage after being released by MPs. Our results reveal that encapsulated bacteriophages are stable and retain their immunogenic properties. Bacteriophage-encapsulated PLGA microparticles may thus represent an important tool for the development of different bacteriophage-based vaccine platforms.

Bovine immune response to leptospira antigen in different novel adjuvants and vaccine delivery platforms

Leptospirosis is a global zoonosis causing significant economic losses for cattle production. Current cattle vaccines against leptospirosis need improvement to provide efficacy against multiple serovars, reduce shedding in urine, and to induce earlier and more robust immune responses. In this study, Leptospira borgpetersenii serovar Hardjo strain 203 antigen was combined with novel adjuvants (a biodegradable polyanhydride compressed rod implant (VPEAR), poly(diaminosulfide) microparticles, a water-oil-water emulsion adjuvant, and aluminum hydroxide) to develop novel vaccines. Cattle were immunized twice, at a 4 week interval, with inoculums containing adjuvants alone or leptospira antigens and immune responses were compared to responses of cattle receiving a commercial monovalent leptospirosis vaccine (Spirovac). All animals were inoculated with a single dose of Spirovac at 20 weeks to assess antigen recall responses. Serum antibody responses were increased (P > 0.05) at 8 and 20 weeks after vaccination in cattle receiving inoculums containing leptospira antigens combined with water-oil-emulsion, poly(diaminosulfide) microparticles (PNSN-MP), or aluminum hydroxide and in cattle vaccinated with Spirovac. Humoral responses were predominantly IgG1 isotypes. Antigen-specific proliferative responses were detected after initial vaccination in cattle vaccinated with Spirovac, PNSN-MP and water-oil-water treatments. Most proliferative responses occurring within CD4+ and gamma delta T cell populations expressing CD45RO and CD25 markers, a response consistent with an effector memory phenotype. Antigen-specific immune responses were not detected in cattle vaccinated with VPEAR after initial inoculation, but were detected in the antigen recall responses. PBMCs from cattle vaccinated with Spirovac, oil-water-oil, or PNSN-MP treatments had increased (P < 0.05) IL-17A release after in vitro stimulation with leptospirosis antigens, whereas all groups produced IFN-γ and IL-17A after in vitro stimulation during the antigen recall response. Our data demonstrates that combining leptospirosis antigens with these adjuvants enhances immunogenicity in cattle.Interpretative Summary: Vaccination of livestock is a key mechanism for minimizing transmission of leptospirosis, a zoonotic disease. Leptospirosis vaccines for cattle need to be improved to provide greater levels of protection from kidney colonization, better immune responses, and protection against multiple serovars. This could be accomplished using new vaccine adjuvants. In this study, several novel adjuvants were evaluated for their ability to induce effective immune responses in cattle to leptospira antigens as compared to currently available vaccines. Data suggested that vaccines containing biodegradable polymer microparticles and oil-emulsion adjuvants induced similar or greater immune responses as compared to a commercial vaccine. Our data suggest these new vaccine formulations warrant further investigation as new vaccine formulations for cattle and other livestock.

Biodegradable Polymer Microparticles with Tunable Shapes and Surface Textures for Enhancement of Dendritic Cell Maturation.

In this report, we present a facile approach to produce biodegradable polymeric microparticles with uniform sizes and controllable morphologies by blending hydrophobic poly(d, l-lactic-co-glycolide) (PLGA) and amphiphilic poly(d, l-lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG) in a microfluidic chip. Microparticles with tentacular, hollow hemispherical, and Janus structures were obtained after complete evaporation of the organic solvent by manipulating the interfacial behavior of emulsion droplets and the phase separation behavior inside the droplets. The number and length of the tentacles on the surface of tentacular microparticles could be tailored by varying the initial concentration and blending ratios of the polymers. The organic solvent played an important role in controlling the morphologies of microparticles. For example, blending PLA16k-b-PEG5k with PLGA100k in dichloromethane resulted in tentacular microparticles, whereas hollow hemispherical microparticles were obtained in trichloromethane. Moreover, these microparticles with controllable shapes and surface textures have significant influence on the immune response of dendritic cells (DCs), showing a morphology-dependent enhancement of DC maturation.

A murine model of cutaneous aspergillosis for evaluation of biomaterials-based local delivery therapies.

Cutaneous fungal infection is a challenging condition to treat that primarily afflicts immunocompromised patients. Local antifungal therapy may permit the delivery of high concentrations of antifungals directly to wounds while minimizing systemic toxicities. However, the field currently lacks suitable in vivo models. Therefore, a large cutaneous wound was created in immunosuppressed mice and inoculated with Aspergillus fumigatus. We fabricated biodegradable polymer microparticles (MPs) that were capable of locally delivering antifungal and characterized in vitro release kinetics. We compared wound bed size, fungal burden, and histological presence of fungi in mice treated with antifungal-loaded MPs. Mice with a cutaneous defect but no infection, mice with infected cutaneous defect but no treatment, and infected mice treated with blank MPs were used as controls. Infection of large wounds inhibited healing and resulted in tissue invasion in an inoculum-dependent manner. MPs were capable of releasing antifungals at concentrations above A. fumigatus Minimum Inhibitory Concentration (MIC) for at least 6 days. Wounds treated with MPs had significantly decreased size compared with no treatment (64.2% vs. 19.4% wound reduction, p = 0.002) and were not significantly different from uninfected controls (64.2% vs. 58.1%, p = 0.497). This murine model may serve to better understand cutaneous fungal infection and evaluate local biomaterials-based therapies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1867-1874, 2019.

Novel Biodegradable Polymeric Microparticles Facilitate Scarless Wound Healing by Promoting Re-epithelialization and Inhibiting Fibrosis.

Despite decades of research, the goal of achieving scarless wound healing remains elusive. One of the approaches, treatment with polymeric microcarriers, was shown to promote tissue regeneration in various in vitro models of wound healing. The in vivo effects of such an approach are attributed to transferred cells with polymeric microparticles functioning merely as inert scaffolds. We aimed to establish a bioactive biopolymer carrier that would promote would healing and inhibit scar formation in the murine model of deep skin wounds. Here we characterize two candidate types of microparticles based on fibroin/gelatin or spidroin and show that both types increase re-epithelialization rate and inhibit scar formation during skin wound healing. Interestingly, the effects of these microparticles on inflammatory gene expression and cytokine production by macrophages, fibroblasts, and keratinocytes are distinct. Both types of microparticles, as well as their soluble derivatives, fibroin and spidroin, significantly reduced the expression of profibrotic factors Fgf2 and Ctgf in mouse embryonic fibroblasts. However, only fibroin/gelatin microparticles induced transient inflammatory gene expression and cytokine production leading to an influx of inflammatory Ly6C+ myeloid cells to the injection site. The ability of microparticle carriers of equal proregenerative potential to induce inflammatory response may allow their subsequent adaptation to treatment of wounds with different bioburden and fibrotic content.

Injectable drug depot engineered to release multiple ophthalmic therapeutic agents with precise time profiles for postoperative treatment following ocular surgery

A multi-drug delivery platform is developed to address current shortcomings of post-operative ocular drug delivery. The sustained biodegradable drug release system is composed of biodegradable polymeric microparticles (MPs) incorporated into a bulk biodegradable hydrogel made from triblock copolymers with poly(ethylene glycol) (PEG) center blocks and hydrophobic biodegradable polyester blocks such as poly(lactide-co-glycolide) (PLGA), Poly(lactic acid) (PLA), or Poly(lactide-co-caprolactone) (PLCL) blocks. This system is engineered to flow as a liquid solution at room temperature for facile injection into the eye and then quickly gel as it warms to physiological body temperatures (approximately 37 °C). The hydrogel acts as an ocular depot that can release three different drug molecules at programmed rates and times to provide optimal release of each species. In this manuscript, the hydrogel is configured to release a broad-spectrum antibiotic, a potent corticosteroid, and an ocular hypotensive, three ophthalmic therapeutic agents that are essential for post-operative management after ocular surgery, each drug released at its own timescale. The delivery platform is designed to mimic current topical application of postoperative ocular formulations, releasing the antibiotic for up to a week, and the corticosteroid and the ocular hypotensive agents for at least a month. Hydrophobic blocks, such as PLCL, were utilized to prolong the release duration of the biomolecules. This system also enables customization by being able to vary the initial drug loading to linearly tune the drug dose released, while maintaining a constant drug release profile over time. This minimally invasive biodegradable multi-drug delivery system is capable of replacing a complex ocular treatment regimen with a simple injection. Such a depot system has the potential to increase patient medication compliance and reduce both the immediate and late term complications following ophthalmic surgery. Statement of SignificanceAfter ocular surgery, patients routinely receive multiple medications including antibiotics, steroids and ocular hypotensives to ensure optimal surgical outcomes. The current standard of care for postoperative treatment after ocular surgery involves using eye drops daily, which has limited effectiveness mainly due to poor patient adherence. To improve patient experience and outcomes, this article presents the first thermoresponsive hydrogel able to release multiple drug molecules for the application of post-operative treatment following ocular surgery. By varying the parameters such as hydrogel type and polymer hydrophobicity, the drug release profile, duration and dosage can finely be tuned. The approach presented in this article can readily be applied to other applications by simply changing the drug loaded in the drug delivery system.

Synergistic approach to localized delivery

Drug Delivery An improved remedy for osteoarthritis could involve localized delivery of an agent to the affected joints to reduce the disease progression, rather than the current use of systemic or local delivery of drugs that only treat the symptoms. Maudens et al. explored the potential for long-term delivery of kartogenin, a pathway activator that enhances articular cartilage protection, by combining two ideas for slow drug release. Using wet milling, they prepared nanocrystals of kartogenin, which dissolve over time, and then embedded them in biodegradable polymer microparticles. The drug-loaded particles were tested in vitro with human synoviocytes and in vivo in a mouse model, in which prolonged delivery and bioactivity of kartogenin were observed. Small 10.1002/smll.201703108 (2018).

Raw starch microparticles have immunostimulant activity in mice vaccinated with BCG and challenged with Mycobacterium tuberculosis

The main challenge for vaccine development or improvement is the lack of safe adjuvants or immunostimulants that induce protective immune responses and can be used for mucosal immunization, which is a highly desirable strategy for vaccination against infectious diseases acquired by oral or intranasal routes. One promising alternative is the use of biodegradable and biocompatible polymeric microparticles. Recently, we developed an immobilization and delivery system with starch microparticles (SMPs) and a starch-binding domain (SBDtag) suitable for the mucosal administration of antigens and the induction of antigen-specific immune responses. Here, we explore the immunostimulant and reinforcing potential of the system using BALB/c mice with progressive pulmonary tuberculosis (PPT). The heat shock protein alpha-crystallin from Mycobacterium tuberculosis immobilized on SMPs (µAcr-SBDtag) or SMPs alone were administered nasally as boosters to BCG-vaccinated mice without any extra adjuvant. The mice were challenged intratracheally with either moderately virulent or highly virulent M. tuberculosis strains. Our results showed that the administration of either the immobilized antigen or SMPs asa booster for the BCG vaccination induced a significant reduction of bacterial loads in the lungs of mice, even more than in mice that received the BCG vaccination alone. Since no difference was observed in pulmonary bacillary burdens between the two reinforced groups, the obtained effect was most likely primarily caused by the starch. As determined by histological study, the administration of boosters did not contribute to the progress of pneumonia, which diminishes the safety concerns related to the administration of SMPs intranasally. Taken together, our findings suggest that this system may be considered asa new carbohydrate-based adjuvant suitable for mucosal vaccines against tuberculosis and other infectious diseases, and more generally, they highlight the potential of particulate α-glucans as immune response modifiers.

Regulation of Drug Release by Tuning Surface Textures of Biodegradable Polymer Microparticles.

Generally, size, uniformity, shape, and surface chemistry of biodegradable polymer particles will significantly affect the drug-release behavior in vitro and in vivo. In this study, uniform poly(d,l-lactic-co-glycolide) (PLGA) and PLGA-b-poly(ethylene glycol) (PLGA-b-PEG) microparticles with tunable surface textures were generated by combining the interfacial instabilities of emulsion droplet and polymer-blending strategy. Monodisperse emulsion droplets containing polymers were generated through the microfluidic flow-focusing technique. The removal of organic solvent from the droplets triggered the interfacial instabilities (spontaneous increase in interfacial area), leading to the formation of uniform polymer particles with textured surfaces. With the introduction of homopolymer PLGA to PLGA-b-PEG, the hydrophobicity of the polymer system was tailored, and a qualitatively different interfacial behavior of the emulsion droplets during solvent removal was observed. Uniform polymer particles with tunable surface roughness were thus generated by changing the ratio of PLGA-b-PEG in the polymer blends. More interestingly, surface textures of the particles determined the drug-loading efficiency and release kinetics of the encapsulated hydrophobic paclitaxel, which followed a diffusion-directed drug-release pattern. The polymer particles with different surface textures demonstrated good cell viability and biocompatibility, indicating the promising role of the particles in the fields of drug or gene delivery for tumor therapy, vaccines, biodiagnostics, and bioimaging.

Low molecular weight poly(3-hydroxybutyrate) microparticles synthesized by piezoelectric spray drying for the sustained release of paclitaxel

Biocompatible and biodegradable polymer microparticles are contemporary medicines able to eliminate the side effects and unsatisfactory pharmacokinetics of already existing preparations. In this work we have developed a high-tech scalable method for the synthesis of paclitaxel-loaded poly(3-hydroxybutyrate) (PHB)-based microparticles. These particles were synthesized on a B-90 Buchi nano spray dryer by piezoelectric spray drying in an inert atmosphere. A regular spherical shape, narrow size distribution, and satisfactory results for the release of paclitaxel from the polymeric matric of microparticles in vitro make this polymeric medicinal form promising for its further application in pharmaceutics. Nanoparticles with a similar composition synthesized via the laboratory one-stage emulsification method were used for comparison. This study is the first stage in the creation of a sustained-action anticancer paclitaxel preparation.

Challenges in the delivery of peptide drugs: an industry perspective.

Due mainly to their poor stability and short plasma half-life, peptides are usually administered by injection, often several times daily. Injectable sustained-release formulations of peptides based on biodegradable polymer microparticles or implants early demonstrated the power of drug delivery technologies to enhance patient adherence and convenience, and increase safety and efficacy. Injectable sustained-release formulations are likely to remain a significant part of new peptide products. However, a new generation of technologies that enable solvent-free formulations and manufacturing processes, injection through narrow gauge needles and ready-to-use presentations will be increasingly used. In addition, the tremendous developments in noninvasive routes of delivery are likely to result in more and more peptides being delivered by the oral, transdermal, nasal or inhalation routes.

Controlled protein release from monodisperse biodegradable double-wall microspheres of controllable shell thickness

Biodegradable polymer microparticles are promising delivery depots for protein therapeutics due to their relatively simple fabrication and facile administration. Double-wall microspheres (DWMS) comprising a core and shell made of two distinct polymers may provide enhanced control of the drug release profiles. Using precision particle fabrication (PPF) technology, monodisperse DWMS were fabricated with model protein bovine serum albumin (BSA)-loaded poly(lactide-co-glycolide) (PLG) core and drug-free poly(d,l-lactic acid) (PDLL) shell of uniform thickness. Monolithic single-wall microspheres were also fabricated to mimic the BSA-loaded PLG core. Using ethyl acetate and dichloromethane as shell- and core-phase solvents, respectively, BSA was encapsulated selectively in the core region within DWMS with higher loading and encapsulation efficiency compared to using dichloromethane as core and shell solvents. BSA in vitro release rates were retarded by the presence of the drug-free PDLL shell. Moreover, increasing PDLL shell thickness resulted in decreasing BSA release rate. With a 14-μm thick PDLL shell, an extended period of constant-rate release was achieved.

Preparation and characterization of Δ9-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines

Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer, AIDS and multiple sclerosis), analgesics, and in the treatment of multiple sclerosis and cancer, among other conditions. However, despite their high clinical potential, only few dosage forms are available to date.In this paper, the development of Δ9-tetrahydrocannabinol (THC) biodegradable microspheres as an alternative delivery system for cannabinoid parenteral administration is proposed. Tetrahydrocannabinol was encapsulated into biodegradable microspheres by the oil-in-water (o/w) emulsion solvent evaporation method. Several formulations were prepared using different drug:polymer ratios. The influence of antioxidant (α-tocopherol acetate) concentration on the release of THC from the microparticles was studied. Elevated process yield and entrapment efficiencies were achieved. The in vitro drug release studies showed that the encapsulated drug was released over a two week period. As THC has shown therapeutic potential as anticancer drug, the efficacy of the microspheres was tested on different cancer cell lines. Interestingly, the microspheres were able to inhibit cancer cell proliferation during the nine-day study period. All the above results suggest that the use of biodegradable microspheres would be a suitable alternative delivery system for THC administration.

Intra-articular controlled release of anti-inflammatory siRNA with biodegradable polymer microparticles ameliorates temporomandibular joint inflammation

We investigated the in vivo therapeutic efficacy of an intra-articular controlled release system consisting of biodegradable poly(dl-lactic-co-glycolic acid) (PLGA) microparticles (MPs) encapsulating anti-inflammatory small interfering RNA (siRNA), together with branched poly(ethylenimine) (PEI) as a transfecting agent, in a rat model of painful temporomandibular joint (TMJ) inflammation. The in vivo effects of PLGA MP dose and siRNA–PEI polyplex delivery were examined via non-invasive meal pattern analysis and by quantifying the protein level of the siRNA target as well as of several downstream inflammatory cytokines. Controlled release of siRNA–PEI from PLGA MPs significantly reduced inflammation-induced changes in meal patterns compared to untreated rats with inflamed TMJs. These changes correlated to decreases in tissue-level protein expression of the siRNA target to 20–50% of the amount present in the corresponding control groups. Similar reductions were also observed in the expression of downstream inflammatory cytokines, e.g. interleukin-6, whose tissue levels in the siRNA–PEI PLGA MP groups were 50% of the values for the corresponding controls. This intra-articular sustained release system has significant implications for the treatment of severe TMJ pain, and also has the potential to be readily adapted and applied to mitigate painful, chronic inflammation in a variety of conditions.