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At least 991 records · Page 55Linked to original sources
PubMed2006

Characterization of pilocarpine-loaded chitosan/Carbopol nanoparticles.

Patients using ophthalmic drops are faced with frequent dosing schedules and difficult drop instillation. Therefore, a long-lasting pilocarpine-loaded chitosan (CS)/Carbopol nanoparticle ophthalmic formulation was developed. The physicochemical properties of the prepared nanoparticles were investigated using dynamic light scattering, zeta-potential, transmission electron microscopy, Fourier transform infrared ray spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The sustained-release effects of pilocarpine-loaded nanoparticles were evaluated using in-vitro release and in-vivo miotic tests, and compared with pilocarpine in solution, gel and liposomes. We found that the prepared nanoparticles were about 294 nm in size. DSC and FT-IR studies suggested that an electrostatic interaction between CS and Carbopol contributes at least in part to the stabilization of pilocarpine/CS/Carbopol nanoparticles. When compared with pilocarpine in solution, gel or liposomes, the best slow-release profile of pilocarpine from the prepared nanoparticles occurred in a dissolution test. In the in-vivo miotic study, pilocarpine-loaded CS/Carbopol nanoparticles showed the most significant long-lasting decrease in the pupil diameter of rabbits. The advantages of CS and Carbopol are good biocompatibility, biodegradability and low toxicity. CS is also a mucoadhesive polymer. Thus, pilocarpine/CS/Carbopol nanoparticles may provide an excellent potential alternative ophthalmic sustained-release formulation of pilocarpine for clinical use. CS/Carbopol nanoparticles may also be useful for a variety of other therapeutic delivery systems.

Acrylic Resins↗
PubMed1999

Genetically engineered polymers for drug delivery.

Genetic engineering methodology offers the ability to synthesize protein-based polymers with precisely controlled structures. Protein-based polymers synthesized by recombinant techniques have a well-defined monomer composition and sequence, stereochemistry, and a narrow molecular weight distribution. The structure of the polymeric carrier at the molecular level influences its biological disposition and drug release profile. Current methodologies of polymer synthesis (chemical polymerization) result in the production of polymers with heterogeneous molecular weights, and with monomer sequences and compositions defined in terms of statistical distributions. Genetic engineering methodologies can be used to design new polymeric drug carriers with improved properties, such as better-defined biorecognition, pharmacokinetic, biodegradation, and drug release profiles. In this review article the rationale and methodology of polymer synthesis using genetic engineering techniques, the status of such polymers in drug delivery to-date, and the potential of these polymers for the development of new systems in the future are discussed.

Drug Delivery Systems↗
PubMed2001

Degradable and injectable poly(aldehyde guluronate) hydrogels for bone tissue engineering.

Degradable and injectable hydrogels may be ideal for bone-tissue engineering, especially in the craniofacial region because of the ease of access for injection. Alginate hydrogels potentially could be used as injectable cell delivery vehicles, but they exhibit a limited range of mechanical properties and uncontrollable disintegration time. Therefore we synthesized new hydrogels, composed of poly(aldehyde guluronate) (PAG) and adipic acid dihydrazide, that have a wide range of mechanical stiffness and controllable degradation rate. MC3T3-E1 cells adhered and multiplied on PAG hydrogels in vitro. When primary rat calvarial osteoblasts were mixed with PAG hydrogels and subcutaneously injected into the backs of mice, mineralized bone tissues were formed 9 weeks following implantation. These hydrogels may find wide utility as an injectable delivery system for bone precursor cells as well as for other applications in tissue engineering.

3T3 Cells↗
PubMed2001

In vivo-in vitro study of biodegradable and osteointegrable gentamicin bone implants.

Three implants composed of phosphate (25% hydroxyapatite, 75% tricalcium phosphate), 20% poly(DL-lactide) (DL-PLA; weight-average molecular weight (Mw), 30 kD) and 3% gentamicin sulphate (GS) were assayed in vitro and in vivo to study their release profiles as potential drug delivery systems to prevent or treat osteomyelitis. To prolong GS release, some implants were coated with poly(lactide-co-glycolide) (PLGA; Mw, 100 kD; I-PLGA) or DL-PLA (Mw, 200 kD; I-PLA). GS levels were measured in bone, kidney and blood after implantation into the femur of rats. The release profiles show a burst in the first few days, followed by a slower release rate. After I-PLA implantation, bone antibiotic concentrations higher than the minimum bactericidal concentration were maintained for 4 weeks. A linear correlation between in vitro and in vivo GS release was found to continue until complete drug release. Histological and radiological analysis showed that the implants were well tolerated and gradual new bone formation was observed.

Absorbable Implants↗
PubMed1996

Development and pharmacokinetics of galactosylated poly-L-glutamic acid as a biodegradable carrier for liver-specific drug delivery.

PURPOSE: A biodegradable carrier for the liver-specific delivery of drugs was developed using poly-L-glutamic acid (PLGA) modified with galactose (galactosylated PLGA or Gal-PLGA), and its feasibility was investigated in mice. METHODS: 111In-PLGA and 111In-Gal-PLGAs were injected in mice and their distribution and biodegradation properties were studied. RESULTS: After intravenous injection. 111In-PLGA was rapidly eliminated from the plasma and recovered mainly in the kidneys and urine. Approximately 15% of the dose was recovered in the liver, predominantly in the nonparenchymal cells. 111In-Gal-PLGAs were taken up by the liver parenchymal cells. Derivatives having 16 or more galactose residues were taken up by the liver to a higher extent (> 60% of the dose). The hepatic clearance of 111In-Gal-PLGAs correlated with their number of galactose residues. 111In-Gal18-PLGA was degraded into low-molecular weight products in the liver. CONCLUSIONS: The advantageous in vivo properties of Gal-PLGA as a liver-specific biodegradable carrier of drugs were demonstrated in mice.

Animals↗
PubMed2005

Insulin containing nanocomplexes formed by self-assembly from biodegradable amine-modified poly(vinyl alcohol)-graft-poly(L-lactide): bioavailability and nasal tolerability in rats.

PURPOSE: The bioavailability and local tolerability of insulin containing nanocomplexes from amine-modified poly(vinyl alcohol)-graft-poly(L-lactide) were studied in rats. Histology of the nasal epithelium was studied to document integrity of the mucosa. METHODS: Nanocomplexes (NC) were prepared by spontaneous self-assembly of insulin and the water-soluble amphiphilic polymer. Changes in blood glucose and insulin blood concentration were monitored in anesthetized rats using a glucose meter and enzyme-linked immunosorbent assay, respectively. Histological sections of the nasal cavity were examined after H&E staining by light microscopy. RESULTS: NC reduced blood glucose level in fasted healthy rats by 20% after 50-80 min and in streptozotocin induced diabetic rats by 30% within 75-95 min compared to basal levels. In both animal models significant concentrations of human insulin were detected, with relative bioavailabilities F(rel) of 2.8 up to 8.3%. The more hydrophobic, lactic acid grafted polyester were more effective at a threefold higher polymer concentration, increasing the relative bioavailability F(rel) of a 5 IU/kg dose from 2.8 to 5.7%. Histological examination of the nasal mucosa after 4 h showed no signs of toxicity at the site of nasal administration. CONCLUSIONS: These results demonstrate that the NC significantly enhanced insulin absorption, suggesting that amphiphilic biodegradable comb-polymers offer a promising approach for nasal peptide delivery.

Administration, Intranasal↗
PubMed1995

Paracrine cytokine adjuvants in cancer immunotherapy.

Advances in our understanding of the molecular events of antigen recognition by T cells and T cell activation are opening up new approaches to cancer immunotherapy. The identification and cloning of cytokines provide one important set of tools for manipulating immunologic responses. For cancer therapy, cytokines such as interleukin-2 have been administered systemically. However, systemic administration of cytokines ignores the paracrine nature of their action. Recently, an alternative approach has been explored that produces high concentrations of cytokines local to the tumor cells. This is achieved either by transduction of the tumor cells with the cytokine gene or by mixture of the tumor cells with cytokine containing biodegradable polymer microspheres. Under these circumstances, the locally released cytokine produces a strong local inflammatory response specific to the particular cytokine. In some cases, a potent tumor-specific T cell response results, capable of mediating regression of systemic tumor deposits. This paracrine delivery of cytokines can therefore be considered as a new type of adjuvant in the design of vaccines for cancer as well as microbial infections.

Adjuvants, Immunologic↗
PubMed2005

Acute toxicity of intravenously administered microfabricated silicon dioxide drug delivery particles in mice: preliminary findings.

BACKGROUND AND OBJECTIVE: Microfabricated particles with nanosized features may serve an important role in the next generation of drug delivery vehicles. Microfabrication (micro-electromechanical systems) technologies offer the promise of both structural elements (e.g., pores, reservoirs) and electromechanical features (e.g., timers, valves, actuators) built into a single particle. In order to serve as carriers to deliver drugs to systemic sites of action, such as tumors, the particles must be safe to administer intravenously. An acute safety study was performed in a mouse model, using intravenous injection of solid silicon dioxide particles created to simulate the size and shape of potential targeted drug delivery vehicles. DESIGN: Two-micron thick, square and circular, parallelepiped-shaped particles were produced with varying sizes of 2 microm, 5 microm and 10 microm using microfabrication techniques and injected into groups of mice (six mice per group) over a range of doses. End-points included acute lethality, clinical signs of toxicity and weight loss. Sections of major organs were sampled for histological examination. RESULTS: At dose levels of 1 x 10(8) particles per mouse, circular particles of 2 microm and 5 microm showed no signs of acute toxicity. Similar results were obtained with the 2 microm and 5 microm square silicon dioxide particles; however, 14-day necropsy indicates fewer 5 microm circular particles in the lung than 5 microm square particles, indicating that the shape of the particles may impact on safety. Acute lethality was observed for 10 microm particles; none of the mice injected with the 10 microm particles survived except at very low dose levels of 6 x 10(5) particles per mouse. CONCLUSIONS: Solid silicon particles greater than 5 microm in their largest dimension are cleared in the lungs and are not safe for intravenous delivery. Particles of 2-5 microm in size do not lodge predominantly in the lung and do not cause acute toxicity, but accumulate in organs such as the liver and spleen. Possible chronic toxicities associated with organ uptake of such non-biodegradable particles have yet to be addressed.

Animals↗
PubMed2004

Drug delivery systems for oestrogenic hormones and antagonists: the need for selective targeting in estradiol-dependent cancers.

The pleiotropic activity of oestrogens and their mechanism of action via their binding to the two oestrogen receptors alpha (ER alpha) and beta (ER beta) subtypes in the different tissues where oestrogens exert their action have been briefly described. The fate of these compounds trapped into different galenic forms is discussed with regard to their therapeutic applications. Firstly, the advantages and disadvantages of the different forms (pills, i.v. forms and transdermal patches) used in contraception are compared. Secondly, the therapeutic use of formulated oestrogens for the post-menopausal hormone replacement therapy (HRT) is analysed through the various results obtained in different trials. The link between HRT and the risks of breast cancer and cardiovascular disease is underlined. Finally, comparing the activity of selective oestrogen receptor modulators such as tamoxifen and pure anti-oestrogens such as RU58668 and ICI182780, we analysed the reasons leading to the need for a tumor targeting of the latters, but not of the former for the treatment of oestrogen-dependent breast cancer. Different injectable and biodegradable formulations, that lead to a remarkable anti-tumor efficiency in xenografts, have been recently developed and we believe that they may represent promising new administration ways of added therapeutic values for anti-oestrogens. Such devices could be extended to the delivery of other anti-cancer drugs with more aggressive activities than anti-oestrogens.

Antineoplastic Agents, Hormonal↗
PubMed1991

A new biodegradable copolymer of glycolic acid and lactones with relatively low molecular weight prepared by direct copolycondensation in the absence of catalysts.

Relatively low-molecular-weight copolyesters of glycolic acid (GA) with lactones such as gamma-butyrolactone (BL), delta-valerolactone (VL), and epsilon-caprolactone (CL) were synthesized by copolycondensation without catalysts. The resulting copolyesters are intended as carriers for drug delivery systems. Copolyesters with approximately 85 mol% GA (number-average molecular weight (Mn): 2900 +/- 100) are crystalline and solid and show a parabolic-type in vivo degradation pattern. The in vivo degradation of amorphous-pasty poly (GA/CL) (approximately 50/50 mol%) changed from parabolic-type to linear-type to S-type pattern as their molecular weight increased. A luteinizing hormone-releasing hormone agonist, [D-Leu6, des-Gly10]-LHRH ethylamide monoacetate (LHRH agonist), was incorporated into small cylinders with these copolyesters. An initial burst of LHRH agonist was observed for cylinders prepared with parabolic-type degrading copolyesters, in contrast to a marked delay in LHRH agonist release for cylinders prepared with S-type degrading copolyesters. The resulting daily dose of drug was maintained an approximately constant, though decreasing stepwise with time. For example, the daily amount of LHRH agonist released in vivo from a cylinder prepared with poly(GA/CL) (50/50 mol%; Mn = 4500) was 61 +/- 39 micrograms/day throughout an experimental period of 10 weeks with a corresponding pharmacological effect on the rat prostate.

Animals↗
PubMed2006

Controlled in vivo degradation of genipin crosslinked polyethylene glycol hydrogels within osteochondral defects.

Polyethylene glycol (PEG) hydrogels show promise as scaffolds for growth factor delivery to enhance cartilage repair. However, methods to control growth factor release in vivo are needed. We have recently shown that in vitro polymer degradation and in vitro growth factor release kinetics can be altered using PEG crosslinked with different concentrations of genipin. However, the degradation and behavior of PEG-genipin in vivo within the cartilage repair site are unknown. This study was conducted to test the hypotheses that the degradation of PEG-genipin can be altered in vivo within osteochondral defects by changing the concentration of genipin, and that PEG-genipin is biocompatible within the mammalian diarthrodial environment. PEG-genipin cylindrical polymers crosslinked using 8mM, 17.6 mM, or 35.2 mM of genipin were implanted into osteochondral defects made in the trochlea of 24 male Sprague- Dawley rats (48 knees). Rats were sacrificed at 5 weeks and gross, cross-sectional, and histologic assessments were performed. Altering the genipin concentration changed the in vivo degradation properties of the hydrogel ( p < 0.01). Consistent with in vitro findings, polymer degradation was inversely related to the concentration of genipin. Near-complete degradation was seen at 8 mM, intermediate degradation at 17.6 mM, and minimal degradation at 35.2 mM. The results of this study show the degradation of PEGgenipin can be altered in vivo within osteochondral defects by changing the concentration of genipin and that PEG-genipin is biocompatible within osteochondral defects. This new in vivo data support potential use of PEG-genipin polymer as an innovative delivery system to control in vivo release of growth factors for improving articular cartilage repair.

Absorbable Implants↗
PubMed2004

Tissue engineering for the replacement of organ function in the genitourinary system.

Acquired and congenital abnormalities may lead to genitourinary organ damage or loss, requiring eventual reconstruction. Tissue engineering follows the principles of cell transplantation, materials science, and engineering toward the development of biological substitutes that would restore and maintain normal function. Tissue engineering may involve matrices alone, wherein the body's natural ability to regenerate is used to orient or direct new tissue growth, or the use of matrices with cells. Both synthetic and natural biodegradable materials have been used, either alone or as cell delivery vehicles. Tissue engineering has been applied experimentally for the reconstitution of several urologic tissues and organs, including bladder, ureter, urethra, kidney, testis, and genitalia. Fetal applications have also been explored. Recently, several tissue engineering technologies have been used clinically including the use of cells as bulking agents for the treatment of vesicoureteral reflux and incontinence and urethral replacement. Recent progress suggests that engineered genitourinary tissues may have clinical applicability in the future.

Humans↗
PubMed2003

Oral insulin--a perspective.

Diabetes mellitus is generally controlled quite well with the administration of oral medications or by the use of insulin injections. The current practice is the use of one or more doses, intermediate or long acting insulin per day. Oral insulin is a promising yet experimental method providing tight glycemic control for patients with diabetes. A biologically adhesive delivery systems offer important advantage over conventional drug delivery systems. The engineered polymer microspheres made of erodable polymer display strong adhesive interactions with gastrointestinal mucus and cellular lining can traverse both the mucosal epithelium and the follicle associated epithelium covering the lymphoid tissue of Peyer's patches. Alginate, a natural polymer recovered from seaweed is being developed as a nanoparticle for the delivery of insulin without being destroyed in the stomach. Alginate is in fact finding application in biotechnology industry as thickening agent, a gelling agent and a colloid stabilizer. Alginate has in addition, several other properties that have enabled it to be used as a matrix for entrapment and for the delivery of a variety of proteins such as insulin and cells. These properties include: a relatively inert aqueous environment within the matrix; a mild room temperature encapsulation process free of organic solvents; a high gel porosity which allows for high diffusion rates of macromolecules; the ability to control this porosity with simple coating procedures and dissolution and biodegradation of the system under normal physiological conditions.

Administration, Oral↗
PubMedDate not supplied

Hydroxyapatite/poly(epsilon-caprolactone) composite coatings on hydroxyapatite porous bone scaffold for drug delivery.

Hydroxyapatite (HA) porous scaffold was coated with HA and polycaprolactone (PCL) composites, and antibiotic drug tetracycline hydrochloride was entrapped within the coating layer. The HA scaffold obtained by a polymeric reticulate method, possessed high porosity ( approximately 87%) and controlled pore size (150-200 microm). Such a well-developed porous structure facilitated usage in a drug delivery system due to its high surface area and blood circulation efficiency. The PCL polymer, as a coating component, was used to improve the brittleness and low strength of the HA scaffold, as well to effectively entrap the drug. To improve the osteoconductivity and bioactivity of the coating layer, HA powder was hybridized with PCL solution to make the HA-PCL composite coating. With alteration in the coating concentration and HA/PCL ratio, the morphology, mechanical properties, and biodegradation behavior were investigated. Increasing the concentration rendered the stems thicker and some pores to be clogged; as well increasing the HA/PCL ratio made the coating surface be rough due to the large amount of HA particles. However, for all concentrations and compositions, uniform coatings were formed, i.e., with the HA particles being dispersed homogeneously in the PCL sheet. With the composite coating, the mechanical properties, such as compressive strength and elastic modulus were improved by several orders of magnitude. These improvements were more significant with thicker coatings, while little difference was observed with the HA/PCL ratio. The in vitro biodegradation of the composite coatings in the phosphate buffered saline solution increased linearly with incubation time and the rate differed with the coating concentration and the HA/PCL ratio; the higher concentration and HA amount caused the increased biodegradation. At short period (<2 h), about 20-30% drug was released especially due to free drug at the coating surface. However, the release rate was sustained for prolonged periods and was highly dependent on the degree of coating dissolution, suggesting the possibility of a controlled drug release in the porous scaffold with HA+PCL coating.

Absorbable Implants↗
PubMed2007

Self-gelling primaquine-gum arabic conjugate: an injectable controlled delivery system for primaquine.

Primaquine, an 8-aminoquinoline, forms a cross-linked gel with periodate-oxidized gum arabic rapidly by simply mixing the drug with the oxidized polysaccharide due to Schiff's base formation between the two amino groups of primaquine and the aldehyde groups in the oxidized polysaccharide. The speed of gelation is determined by the degree of oxidation of polysaccharide, its quantity, and the drug payload. Estimation of the cross-linking density of the gels showed that the higher is the degree of oxidation of gum arabic, the higher is the cross-linking density. In vitro release of primaquine into phosphate buffered saline (PBS) at 37 degrees C demonstrated that the extent of release depended on the cross-linking density and drug payload. Repeated extraction using PBS soon after gel formation showed that not all of the primaquine was conjugated to the polysaccharide and the release seen in vitro was mostly from the unconjugated drug especially from matrices with higher cross-linking density. The gels were found to degrade in PBS, the kinetics of degradation being dependent on the cross-linking density. Cytotoxicity evaluation using MTT assay against L929 mouse fibroblasts showed that oxidized gum arabic having a degree of oxidation of 50% was only very mildly cytotoxic at a concentration of 0.025 g/mL. An injectable, biodegradable drug depot with controlled release of primaquine over several days or weeks would be advantageous for long-term delivery of this drug against malaria or leishmaniasis, and the present study shows that a primaquine-polymer conjugate that can be formed in situ could be an interesting possibility.

Animals↗
PubMedDate not supplied

Bioavailability of microsphere-entrapped cyclosporine A in the cornea and aqueous of rabbits.

Extended release of immunosuppressive drugs and sustained drug levels are desirable for the treatment of corneal graft rejection and other ocular immune disorders. This experiment was conducted with biodegradable microspheres containing cyclosporine A to assess their suitability for achieving this goal. Microspheres containing cyclosporine A were prepared using a solvent evaporation process. A mixture of poly(lactic) and poly(glycolic) acid polymers (50:50) and cyclosporine A was dissolved in a mixture of chloroform and acetone. The solution was then emulsified in an aqueous solution of polyvinyl alcohol and stirred for 24 hours to evaporate the organic solvent. The final assayed concentration of cyclosporine A was 15.38 mg/mL. A 0.13 mL aliquot (2.0 mg) of the suspension of the microspheres was injected subconjunctivally in 24 eyes of white New Zealand rabbits. The concentration of cyclosporine A in the aqueous and cornea was measured at 6, 12, 24, 48, 72, and 144 hours after injection (n = 4 for each group). Corneal levels of cyclosporine A ranged from 2392 +/- 70 ng/mL at 6 hours to 1297 +/- 459 ng/mL at 144 hours. The aqueous levels ranged from 110 +/- 0 ng/mL at 6 hours to 62 +/- 11 ng/mL at 144 hours. These data indicate that a microsphere drug delivery system is an effective means of delivering cyclosporine A to the cornea and anterior chamber, and may provide an alternative for the treatment of ocular immune disorders.

Animals↗
PubMed2004

Novel long-circulating liposomes containing peptide library-lipid conjugates: synthesis and in vivo behavior.

Rapid uptake of intravenously injected liposomes by the mononuclear phagocyte system has limited their use as drug delivery vehicles. Recently, various long-circulating liposomes have been prepared by incorporating glycolipids or other amphiphilic molecules into the lipid bilayer of conventional liposomes. The purpose of the present study was to design a new class of biodegradable membrane modifiers that would increase the half-life of liposomes in vivo. Using solid-phase peptide synthesis, synthesized were 30-residue random libraries consisting of a random sequence of glycine, beta-alanine and gamma-aminobutyric acid. The libraries were coupled to stearic acid (SA) or phosphatidylethanolamine (PE). The resulting amphiphilic conjugates were mixed with egg phosphatidylcholine (PC) and cholesterol (Chol) in a 6:47:47 ratio, and unilamellar liposomes were prepared. For comparison, plain PC/Chol (50:50) liposomes, as well as liposomes containing polyethylene glycol (PEG)-SA/PC/Chol (6:47:47) and PEG-PE/PC/Chol (6:47:47) were also prepared. Calcein was entrapped in the liposomes, which were given intravenously to rats at a dose of 9.2 mumol lipid/kg, and the amount of intact liposomes present in serum was followed with time. While the conventional liposomes had a short elimination half-life (28 min), the liposomes modified with library-PE had a much longer half-life (170 min), while library-SA provided no improvement of the liposome pharmacokinetics. PEG-PE greatly improved the half-life of the liposomes (400 min) while PEG-SA only provided a marginal improvement. All liposome preparations were cleared in a biphasic fashion. In conclusion, a novel biodegradable lipopeptide conjugate was designed that endows liposomes with a prolonged circulation time in vivo. The pharmacokinetic profile of these modified liposomes was drastically improved over that of conventional liposomes. Since the library is prepared by solid-phase synthesis, length and/or composition could easily be modified in order to modulate the clearance profile of the liposomes. Tailoring of the pharmacokinetic profile of the liposomes depending on their intended application may allow for a greater flexibility of use than PEG-PE.

Animals↗
PubMed1995

The role of prostaglandins in bone formation.

Prostaglandins of the E series have been shown to be effective inducers of bone formation in vivo. In this study, the effects of PGE2 were evaluated in vivo using subcutaneous administration (3 mg/kg/d for 25 days) to ovariectomized rats or local application in the marrow cavity of tibiae of rats using biodegradable implants (0.13, 1.4 and 32 microg released over 8 days). Systemic treatment of rats with PGE2 stimulated cancellous bone formation in the metaphysis of the proximal tibiae as well as endocortical bone formation and de novo trabecular bone formation in the marrow cavity. Local delivery of PGE2 increased cancellous bone volume in the secondary spongiosa and cortical thickness (at 32 microg). Comparisons of prostanoid effects in vitro, in a bone-derived cell line, showed that PGF2alpha was a better stimulator of DNA synthesis than PGE2. PGF2alpha increased the steady state levels of IGF-I receptor mRNA while PGE2 increased IGF-I expression. Although the mechanism of bone formation by PGE2 is not known at this time, it is clear that PGE2 has powerful local anabolic effects on bone formation in vivo possibly by mediating responses to signals such as changes in mechanical force.

Animals↗