Iontophoresis Research Articles

Characterization of Ocular Iontophoretic Drug Transport of Ionic and Non-ionic Compounds in Isolated Rabbit Cornea and Conjunctiva.

Ocular iontophoresis (IP) in isolated rabbit cornea and conjunctiva was examined in terms of transport enhancement, tissue viability and integrity using electrophysiological parameters by the Ussing-type chamber technique. Lidocaine hydrochloride (LC, a cationic compound), sodium benzoate (BA, anionic compound), and fluorescein isothiocyanate labeled dextran (molecular weight 4400 Da, FD-4, hydrophilic large compound) were used as model permeants. Direct electric current was applied at 0.5-5.0 mA/cm(2) for the cornea and 0.5-20 mA/cm(2) for the conjunctiva for 30 min. LC and BA fluxes across the cornea and conjunctiva were significantly increased by the application of electric current up to 2.3- and 2.5-fold and 4.0- and 3.4-fold, respectively, and returned to their baseline level on stopping the current. Furthermore, a much higher increase by IP application was obtained for the FD-4 transport. The increased FD-4 flux in the conjunctiva returned to baseline on stopping the current, whereas the flux in the cornea was sustained at a higher level after stopping the current. The transepithelial electric resistance of the cornea and conjunctiva was lowered by electric current application but fully recovered after stopping the current up to 2.0 mA/cm(2) for the cornea and 10 mA/cm(2) for the conjunctiva, suggesting that the corneal and conjunctival viability and integrity are maintained even after application of these current densities. These results indicate that ocular IP may be a useful non-invasive technique to achieve drug delivery of hydrophilic large molecules into the eyes.

Physiological approaches to understanding molecular actions on dorsolateral prefrontal cortical neurons underlying higher cognitive processing.

Revealing how molecular mechanisms influence higher brain circuits in primates will be essential for understanding how genetic insults lead to increased risk of cognitive disorders. Traditionally, modulatory influences on higher cortical circuits have been examined using lesion techniques, where a brain region is depleted of a particular transmitter to determine how its loss impacts cognitive function. For example, depletion of catecholamines or acetylcholine from the dorsolateral prefrontal cortex produces striking deficits in working memory abilities. More directed techniques have utilized direct infusions of drug into a specific cortical site to try to circumvent compensatory changes that are common following transmitter depletion. The effects of drug on neuronal firing patterns are often studied using iontophoresis, where a minute amount of drug is moved into the brain using a tiny electrical current, thus minimizing the fluid flow that generally disrupts neuronal recordings. All of these approaches can be compared to systemic drug administration, which remains a key arena for the development of effective therapeutics for human cognitive disorders. Most recently, viral techniques are being developed to be able to manipulate proteins for which there is no developed pharmacology, and to allow optogenetic manipulations in primate cortex. As the association cortices greatly expand in brain evolution, research in nonhuman primates is particularly important for understanding the modulatory regulation of our highest order cognitive operations.

Synergistic iontophoretic drug delivery of risedronate sodium in combination with electroporation and chemical penetration enhancer: In‐vitro and in‐vivo evaluation

In the present investigation iontophoretic permeation of risedronate sodium (RS) through optimized gel based formulation was evaluated with respect to various electrical parameters like Current density and type of current. The study also involved enhancement the iontophoretic permeation of RS in combination with electroporation and chemical penetration enhancers with its in‐vivo Pharmacokinetic evaluation.The permeation studies were carried through the human cadaver skin by using modified Franz diffusion cell and microcontroller based devices for iontophoresis and electroporation developed in the laboratory. In‐vivo Pharmacokinetic studies were carried out in hairless rats. One way ANOVA followed by Tukey‐Kramer test for multiple comparisons. The permeation of RS was significantly increased with iontophoresis at 0.5 mA/Cm2 current density.The iontophoretic permeation was found depend on current density and ON:OFF ratio.The pulsatile current resulted in high permeation than continuous current. Maximum permeation was obtained at 0.5 mA/cm2 with 1:1 pulsed current. When iontophoresis was coupled with chemical penetration enhancers and electroporation for 100 ms at 220V, synergistic enhancement in permeation was observed with shortened lag time and high flux. The required flux was achieved with area of application 1.55 cm2. In‐vivo studies in hairless rats revealed high Cmax, low tmax and increased area under the curve with electroporation, followed by iontophoresis indicated increased bioavailability. Relative bio‐availability was 4.6 when calculated in comparison to passive studies. Key words: Electroporation, iontophoresis, penetration enhancers, risedronate sodium

Aquagenic keratoderma treated with tap water iontophoresis.

Aquagenic keratoderma (AK) is a rare acquired skin condition characterized by recurrent and transient white papules and plaques associated with a burning sensation, pain, pruritus and/or hyperhidrosis on the palms and more rarely, soles triggered by sweat or contact with water. Often AK cause significant discomfort, thus requiring an appropriate therapy. Topical aluminum-based products are the most commonly used medications, but they are not always effective. We report a case of AK unresponsive to topical 20% of aluminum chloride successfully treated with tap water iontophoresis.

Microneedle and iontophoresis based products

Microneedle and iontophoresis based products

Experimental study of iontophoresis-mediated corneal collagen crosslinking for rabbit Staphylococcus aureus keratitis

Background It is determined that riboflavin/ultraviolet A (UVA)-induced corneal collagen crosslinking is able to increase resistance of cornea against enzymatic digestion and has antimicrobial efficacy for various kinds of bacteria in vitro.However,its in vivo study is less now.Objective This study aimed to evaluate the efficacy of iontophoresis-mediated corneal collagen crosslinking combined with or without drugs for Staphylococcus aureus keratitis.Methods Bacterial keratitis models were induced by the interstromaly injection of Staphylococcus aureus suspension with concentration 2× 109/ml in the right eyes of 40 rabbits,and then the rabbits were randomly classified into the model group,gatifloxacin eye drops group,riboflavin/UVA corneal crosslinking group and drugs+ crosslinking group.The smearing of corneal surface was performed for the identification of bacteria 24 hours after injection.Iontophoresis-mediated riboflavin/UVA crosslinking was applied on the eyes of the riboflavin/UVA corneal crosslinking group and drugs+crosslinking group,and gatifloxacin eye drops was topically used 7 times per day on the eyes of the gatifloxacin eye drops group and drugs+crosslinking group.The corneal inflammation was examined and graded under the slit lamp biomicroscope before and after treatment.Ocular anterior segment optical coherence tomography(AS-OCT),corneal histopathology and ultrastructure were examined 14 days after treatment.The living environment of the experimental animals was maintained at 21 ℃ with a 12-hour light and dark cycle.Animals used in this study were treated in accordance with the Weifang Medical College Animal Experimentation Ethic Committee (AEEC) guidelines.The study protocol was approved by the AEEC.Results Corneal inflammation and ulcer were observed,but no significant difference was found in the inflammatory grade among the 4 groups 24 hours after injection (x2=0.293,P＞0.05).In the 14th day after injection,the corneal ulcer area was smaller and corneal edema was milder in the drugs+crosslinking group compared with the model group,gatifloxacin eye drops group and riboflavin/ UVA corneal crosslinking group,showing a significant difference in the inflammatory grade among them (x2 =38.710,P＜0.001).The cornea thickness values of ulcer zone were (428.1 ± 146.2) μm on the 14th postinjected day in the drugs+crosslinking group,which was evidently higher than those in the model group,gatifloxacin eye drops group and riboflavin/UVA corneal crosslinking group,with a significant difference among the 4 groups (F =8.310,P＜0.001).A lower degree of destruction of cornea collagen and less inflammatory cells were seen in the cornea tissue of the drugs+ crosslinking group by haematoxylin and eosin staining in comparison with other 3 groups,and normal keratocytes were much more in the drugs + crosslinking group than those in other treated groups.Conclusions Iontophoresismediated corneal collagen crosslinking can alleviate Staphylococcus aureus keratitis.The combination of crosslinking with drugs has a better effectiveness than the administration of gatifloxacin eye drops only or riboflavin/UVA corneal crosslinking only. Key words: Iontophoresis; Collagen crosslinking; Ultraviolet ray; Cross-linking reagent; Riboflavin; Staphylococcus aureus ; Keratitis

Transdermal delivery of proteins using a combination of iontophoresis and microporation.

This study aimed to investigate transdermal delivery of proteins using combination of microporation and iontophoresis (ITP). Materials & methods & results: Delivery of model protein, Alexa Fluor 555 bovine serum albumin conjugate (AF-BSA) using ITP alone, microneedle (MN) alone, and ITP plus MN combination was assessed using confocal microscopy. Compared to MN alone, combination of MN plus ITP significantly increased skin's penetration depth of AF-BSA (300 vs 110 μm) and achieved lateral distribution of the model protein. Average fluorescence intensity quantified around each microchannel was 23.7-fold (8.2-fold, in vivo) higher for combination treatment compared with MN alone, in vitro. After 1 h in vitro permeation study, the unlabeled BSA amount delivered across skin was found to be 0, 1.4, 0.63 and 14 μg by passive, MN alone, ITP alone and ITP plus MN combination delivery, respectively.

Teva Outbids Endo to Secure NuPathe Acquisition

Teva Pharmaceutical Industries has outbid Endo Health Solutions with a deal to buy neurology specialist NuPathe for US$144 M upfront in order to gain access to Zecuity® (sumatriptan iontophoretic transdermal system), a prescription migraine patch that was approved by the US FDA in January 2013. NuPathe shareholders also stand to receive up to US$3.15 per share in contingent consideration linked to net sales levels of the product. Teva is in need of new sources of revenue ahead of the arrival of generic competition on its key asset Copaxone® (glatiramer acetate), which could occur in June 2014.

The effect of L-arginine on microvascular reactivity in normotensive subjects with a family history of hypertension

Background : An increasing number of studies support the hypothesis that endothelial dysfunction due to reduced availability of nitric oxide plays a key role in initiation, development and progression of essential hypertension. The aim of our study was to determine whether the ingestion of L-arginine actually improves microvascular function in normotensive subjects with a family history of hypertension. Methods : 30 normotensive healthy men, aged 20–30 years, were divided into two groups according to the family history of hypertension. We measured ECG, heart rate, systolic and diastolic arterial pressure, cardiac output, stroke volume, total peripheral resistance (Task Force Monitor) and laser Doppler (LD) flux in the microvessels of the skin on the forearm at rest, before and after the administration of 0.9 g L-arginine. The endothelium-dependent vasodilation was assessed by iontophoresis of acetylcholine and the endothelium-independent vasodilation by iontophoresis of sodium nitroprusside. Results : After the ingestion of L-arginine the heart rate and the cardiac output statistically significantly decreased in both groups (paired t-test, p < 0.05). Arterial pressure did not change significantly. Stroke volume decreased and total peripheral resistance increased only in the group of subjects with a family history of hypertension (paired t-test, p < 0.05) The ingestion of L-arginine in predisposed normotensive subjects acutely improved the endothelium-dependent vasodilation (Dunnett’s test, p < 0.05), which is consistent with the assumption that endothelial dysfunction is already present in these subjects. Conclusions : In subjects with a family history of hypertension L-arginine improved endothelial function. This justifies L-arginine as a potential agent for the prevention and/or treatment of arterial hypertension.

Effect of Lipophilicity on Microneedle-Mediated Iontophoretic Transdermal Delivery Across Human Skin In Vitro

The effect of lipophilicity of drug on the microneedle (MN)-mediated iontophoretic delivery across dermatomed human skin was studied. Beta blockers with similar pKa but varied log P values were selected as model drugs in this study. Iontophoresis (ITP) or MNs, when used independently, increased the transdermal flux of beta blockers as compared with passive delivery (PD). ITP across the MN-treated skin (MN + ITP) increased the permeation rate of all beta blockers as compared with PD (p < 0.001). The enhancement ratios (ER) for hydrophilic molecules (atenolol and sotalol) were 71- and 78-fold higher for ITP + MN as compared with PD. However, for lipophilic molecule such as propranolol, there was 10-fold increase in the ER as compared with PD. These observations were further substantiated by the skin retention data; an inverse relationship between the skin retention and the hydrophilicity of the drug was observed. The results in the present study point out that the lipophilicity of the molecule plays a significant role on the electrically assisted transdermal delivery of drugs across the microporated skin. Using the combination of ITP + MN, hydrophilic drugs (atenolol and sotalol) were delivered at a much higher rate as compared with lipophilic molecules (propranolol and acebutolol).

The Medicines Company Strengthens its Perioperative Care Franchise via Deals with Incline Therapeutics and BMS

The Medicines Company (TMC) has agreed to acquire Incline Therapeutics, which is pursuing the development of Ionsys® (fentanyl iontophoretic transdermal system), a needleless, patient-controlled analgesia device for the short-term management of acute postoperative pain. Cadence Pharmaceuticals obtained an exclusive option to acquire Incline in 2010 but this will be terminated on completion of the purchase of Incline by TMC. On the same day as the Incline deal, TMC also announced a 2-year global licence and collaboration agreement for Bristol-Myers Squibb’s Recothrom®, a US FDA approved topical recombinant thrombin to control non-arterial bleeding during surgery.

Active enhancement methods for intra- and transdermal drug delivery: a review.

Transdermal route has some advantages over other drug administration routes. These include avoidance of first pass effect (hepatic metabolism), better pharmacokinetic profile, reduction of side effects and good patient compliance. The greatest obstacle for the drugs to be delivered through the skin is overcoming the impermeable outermost layer of the skin – the stratum corneum. Quite a few enhancement techniques can be used to overcome the stratum corneum barrier and facilitate transdermal drug delivery. These include various passive (penetration enhancers, liposomes) and active approaches (electroporation, iontophoresis, microneedles), which are of prime interest for transdermal drug delivery research area.

Herbal iontophoresis and rotation manipulation management on lumbar disc herniation

Objective To observe the curative effect of herbal iontophoresis with rotation manipulation treating lumbar disc herniation.Methods 84 patients from July 2011 to July 2012 with lumber disc herniation in Electric Power hospital of Capital Medical University were randomly divided into two groups (a testing group n=42,a control group n=42).The testing group was treated with herbal iontophoresis and rotation manipulation,and the control group was treated with rotation manipulation only.The Visual Analogue Scale and Macnab standard for curative effect were observed before the treatment and 3 weeks later after the treatment.Results The total effective rate was 88.1％ and 66.7％ in the testing group and the control group respectively,the difference between two groups was statistically significant (chi-square=5.51,P=0.02＜0.05).The VAS before and after treatment in testing group were (7.31±1.39) and (2.41±1.62) respectively,compared with (7.19± 1.38) and (3.07± 1.28) in the control group.The VAS and curative effect indexes were both improved in the two groups,but the testing group increased more apparent,and the difference between the two groups was significant (P＜0.05).Conclusion The curative effect of herbal iontophoresis and rotation manipulation treating lumber disc herniation was sound. Key words: Conservative treatment; Lumber disc herniation; Manipulation

Research progress in non-invasive glucose monitoring based on the reverse iontophoresis

无创血糖检测是近年来血糖检测的主要发展方向.基于反向离子电渗透原理的检测技术是进行血糖无创检测的方法之一,它可以实现糖尿病患者血糖浓度的实时监控和及时检测,对预防并发症的发生有重要意义.详细介绍了反向离子电渗透的原理、组织间液的提取以及低浓度葡萄糖传感器的设计方法；概述了基于反向离子电渗透原理的无创血糖检测的国内外研究现状以及利用这项技术进行皮下组织液里其它物质提取与检测的相关研究；最后讨论了反离子电渗透无创血糖检测技术存在的关键问题和解决方法,为进行组织液的提取和葡萄糖浓度的检测以及基于反离子电渗透技术无创血糖检测仪的研制打下基础。

Methods to improve transdermal delivery of aminolevulinic acid

Aminolevulinic acid-based photodynamic therapy (ALA-PDT) has been extensively applied in dermatology.However,the low permeability of ALA across intact skin has limited the efficacy of ALA-PDT.To enhace the percutaneous penetration of ALA,esterified derivatives,microneedles,laser,iontophoresis,delivery vehicles have been used in succession,and some achievements have been made.These methods can increase the transdermal delivery of ALA in terms of depth and quantity by different mechanisms,and indirectly promote the efficacy of ALA-PDT in dermatoses. Key words: Photochemotherapy; Aminolevulinic acid; Transdermal; Delivery vehicles

Transdermal iontophoresis: a non-invasive treatment method for chemotherapy-induced nausea and vomiting with elevated patient's compliance

Transdermal iontophoresis: a non-invasive treatment method for chemotherapy-induced nausea and vomiting with elevated patient's compliance

A Survey on the Effects of Iontophoresis of Piroxicam Gel on Pain and Knee Muscles Strengthn Patients with Knee Osteoarthritis

Background and Aim: Knee osteoarthritis is the most common cause of disability in many societies. Therapeutic measures such as using anti-inflammation drugs and physiotherapy programs have been used to suppress knee pain and improve knee joint function in patients with knee osteoarthritis. The aim of this study was to compare the effects of iontophoresis of piroxicam gel, galvanic current with or without piroxicam gel on pain, functional ability and knee muscle strength in patients with knee osteoarthritis. Materials and Method: This study was a clinical trial conducted in Akhtar hospital. Forty two female patients (mean age 58.52 years old) with knee osteoarthritis participated in this study. The protocol was performed in Physiotherapy Clinic of Mazandaran Medical University, Mazandaran, Iran. All patients were randomly assigned to three groups. Iontophoresis of piroxicam gel was applied for group 1 (n=14), proxicam gel for group 2 (n=14) and galvanic current for group 3 (n=14). The procedure was carried out for 20-minutes, three times a week and for two following weeks. Knee pain and functional ability were estimated by knee injury and osteoarthritis outcome score (KOOS) questioner and the strength of knee extensor and flexor muscles by an isometric device just before the first treatment and immediately after the last treatment times. Results : A significant decrease in pain and a significant increase in functional ability and the strength of knee extensor muscles were resulted in all studied groups (P p) ولی نتایج حاصله نشان داد كه در بین سه گروه نيز اختلاف معنی داری آماری وجود داشت (01/0> P) و استفاده از یونتوفورزیس پیروکسیکام برای کاهش درد، بهبود عملکرد زانو از دیگر روش ها موثرتر بوده است. واژگان کلیدی یونتوفورزیس، ژل پیروکسیکام، درد، قدرت عضلات، استئوارتریت زانو [1] . Knee injury and Osteoarthritis Outcome Score 1. Nisha G, Nancy E. Osteoarthritis: Current Concepts in Diagnos and Managemen. AmFam physician. 2000; 61(6): 1795- 1804. 2. Banwell B.F, Gall V. Physical therapy management of arthritis. First Edition. New York: Churchill Living Stone, 1998; p 8-11. 3. David C, Lioyd J. Rheumatological physiotherapy. First Edition. London: Mosby, 1999; p 83-96. 4. Akinbo S.R , Aiyejusunle C.B , Akinyemi O.A , Adesegun S.A .Comparison of the therapeutic efficacy of phonophoresis and iontophoresis using dexamethasone sodium phosphate in the management of patients with knee osteoarthritis. Journal of Niger Postgrad Medicin e. 2007; 14(3): 190-194. 5. Rahimi A .The new of Osteoarthritis. First Edition.Tehran: Sarmadi, 1385: p 18-42. [in Persian] 6. Bijlsma J.W.J, Knahr K .Strategies for the prevention and management of osteoarthritis hip and knee. Best Practice & Research Clinical Rheumatology. 2007; 21(1 ): 59-76. 7. Kopec J, Mushfiqur R. Epidemiology of osteoarthritis in British. Journal of Rheumathology. 2007; 37(2): 386-393. 8. Armando M, Eduardo E .Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. The American Journal of Medicine . 1987; 83(5) : 72-77. 9. Gibson J. A. Survey of patients’ knowledge of gastrointestinal side-effects of NSAIDs in a rheumatology clinical. Quality in Primary Care . 2006; 14(2): 95-97. 10. Haynes S, Gemmell H .Topical treatments for osteoarthritis of the knee. Clinical Chiropractic . 2007; 10(3): 126-138. 11. Bakhtiary A. H. Principles and Practice of electrical current. First Edition. Samnan; Bakhtiary, 1381: 31- 45. [in Persian] 12. Curdy C, Yogeshvar K. Piroxicam delivery into human stratum corneum in vivo: iontophoresis versus passive diffusion. Journal of Controlled Release . 2001; 76 (1-2): 73-79. 13. Aiyejusunle C.B , Kola T.A , Ajiboye O.A . Comparison of the effects of tens and sodium salicylate iontophoresis in the management of osteoarthritis of the knee. Journal of Nig Q Hosp Medicin e. 2007; 17(1): 30-4. 14. Nelson R. Clinical Electrotherapy. Third edition .United States of America: Mary Ellen McCourt, 1999; p 116-117. 15. Fransen M, Crosbie J. Isometric Muscle Force Measurement for Clinicians Treating Patients With Osteoarthritis of the Knee . Journal of Arthritis & Rheumatism. 2003; 49(1): 29-31. 16. Cosignani F , Cossu M , Pancer E , Rega V , Conti B. Clinical study on effect of ketoprofen administered by iontophoresis. Riabilitazione . 1987; 20 (4): 269-273. 17. Baskurt F , Ozcan A , Algun C . Comparison of effects of phonophoresis and iontophoresis of naproxen in the treatment of lateral epicondylitis. Clinical Rehabilitation . 2003; 17(1): 96-100. 18. Hurley MV, Scott Dl . Rehabilitation reduces disability in patients with knee osteoarthritis . Journal Citations Anu Meet Int Soc Technol Assess Health Care, Int Soc Technol Assess Health Care Meet. 1999; 15: 153. 19. Fransen M , Crosbie J . Isometric Muscle Force Measurement for Clinicians Treating Patients With Osteoarthritis of the Knee . Journal of Arthritis & Rheumatism 2003 ; 49(1): 29-35.

In Vivo Iontophoretic Delivery of Salmon Calcitonin Across Microporated Skin

The purpose of this study was to determine the effect of microneedle (MN) technology and its combination with iontophoresis (ITP) on the in vivo transdermal delivery of salmon calcitonin (sCT). Maltose MNs (500 µm) were used to porate skin prior to application of the drug, with or without ITP. Micropores created by maltose MNs were characterized by histological sectioning and calcein imaging studies, which indicated uniformity of the created micropores. In vivo studies were performed in hairless rats to assess the degree of enhancement achieved by ITP (0.2 mA/cm² for 1 h), MNs (81 MNs), and their combination. In vivo studies indicate a serum maximal concentration of 0.61 ± 0.42 ng/mL, 1.79 ± 0.72 ng/mL, and 5.51 ± 0.32 ng/mL for ITP, MNs, and combination treatment, respectively. MN treatment alone increased serum concentration 2.5-fold and the combination treatment increased the concentration ninefold as compared with iontophoretic treatment alone. Combination treatment of ITP and MNs resulted in the highest delivery of sCT and therapeutic levels were achieved within 5 min of administration.

A Phase I, single center, open label, randomized, single-dose, two way crossover study to compare the pharmacokinetics of two NP101 patch applications (sumatriptan iontophoretic transdermal system) with and without controlled heat

A Phase I, single center, open label, randomized, single-dose, two way crossover study to compare the pharmacokinetics of two NP101 patch applications (sumatriptan iontophoretic transdermal system) with and without controlled heat

In Vivo Calcium and Phosphate Iontophoresis for the Topical Treatment of Osteoporosis

In addition to systemic treatment, osteoporosis may be treated topically by incorporating calcium and phosphate into the bone. This article describes the use of a recently developed, novel iontophoretic apparatus suitable for local ion delivery into bones. In this study, in vivo experiments were performed to compare the effects of local electrotherapy and those of systemic hormone replacement on bone. In this study, local iontophoresis was carried out in ovariectomized and control rats. Bone density, biomechanical, and elemental studies were performed. Forty 12-week-old Sprague-Dawley rats received an ovariectomy (OVX) or were sham-operated (sham). Twenty-one weeks later, tibias of subgroups of sham-operated and OVX animals were subjected to serial local iontophoresis (IOP) treatments, received systemic subcutaneous 17β-estradiol (E2), or were treated with the combination of IOP and E2. Changes in bone density were detected by quantitative ultrasound densitometry and expressed as amplitude-dependent speed of sound (AD-SoS). Biomechanical studies and elemental analysis were performed at the end of the experiments. Osteopenia developed 21 weeks after OVX in the proximal tibial regions; the mean difference estimate (95% confidence intervals) of AD-SoS values between the sham-operated and OVX animals was 188.7 (140.4-237.1). Serial iontophoretic treatment resulted in an increase in bone density in both sham-operated and OVX animals (sham+IOP versus sham: 121.4 [73.01-169.7]; OVX+IOP versus OVX: 241.6 [193.2-289.9]). Similar changes in AD-SoS were detected after 17β-estradiol (E2) treatment; however, even greater changes occurred after OVX+E2+IOP versus OVX+E2 (123.4 [75.1-171.8]). Similar improvements also were evident regarding the biomechanical features of the tibias. A limitation of this study was the relatively small number of rats. The efficacy of local IOP using calcium- and phosphate-donating microparticles is comparable to that of estrogen therapy as evidenced by steadily increasing bone density, restoration of the calcium and phosphate balance, and improvement in the biomechanical properties of the bone.