Sustained-release Delivery System Research Articles

Proliferation and apoptosis of male germ cells in captive Atlantic bluefin tuna ( Thunnus thynnus L.) treated with gonadotropin-releasing hormone agonist (GnRHa)

The effects of administration of gonadotropin-releasing hormone agonist (GnRHa) on proliferation and apoptosis of male germ cells were evaluated on Atlantic bluefin tuna ( Thunnus thynnus L.) reared in captivity. Fish ( n = 19) were treated with a sustained-release delivery system loaded with GnRHa during the natural spawning season of 2004 and 2005 (June–July). Untreated Control fish ( n = 17) and adult wild spawners were used for comparison. Fish were sacrificed 2–8 d after GnRHa implantation and body weight and gonad weight were recorded, and gonads and blood were taken. Germ cell proliferation and apoptosis were evaluated through the immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and the terminal deoxynucleotidyl transferase-mediated d’UTP nick end labelling (TUNEL) method, respectively. Plasma 11 ketotestosterone (11-KT) levels were measured using an ELISA method. Mean gonado-somatic index and seminiferous lobule diameter did not differ between GnRHa-treated and Control fish, and were significantly lower in captive-reared individuals than in wild spawners. Significant increases in 11-KT plasma levels and spermatogonial mitosis, along with a reduction of germ cell apoptosis were demonstrated in GnRHa-treated fish compared to Controls. The results suggest that GnRHa administration was effective in enhancing germ cell proliferation and reducing apoptosis in captive males through the stimulation of luteinizing hormone (LH) release and testicular 11-KT production.

Imprinted hydrophilic nanospheres as drug delivery systems for 5-fluorouracil sustained release

Molecularly imprinted hydrogel nanospheres as devices for the controlled/sustained release of 5-fluororacil in biological fluids were synthesized employing one-pot precipitation technique as the polymerization method. Methacrylic acid as a functional monomer and ethylene glycole dimethacrylate as a cross-linker were used in polymeric feed. Morphological and hydrophilic properties were determined by scanning electron microscopy and water content measurement, and recognition and selectivity properties of spherical molecularly imprinted polymers were compared with the spherical non-imprinted polymers, both in organic (acetonitrile) and water media. Finally, in vitro release studies were performed in plasma simulating fluids.

Floating bioadhesive drug delivery system using novel effervescent agents

Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from the upper gastrointestinal tract and improve the bioavailability of medications that are characterized by the narrow absorption window. A new gastroretentive sustained release delivery system using the novel effervescent system was developed with floating, swellable, and bioadhesive properties. Various release retarding polymers like psyllium husk, HPMC K15M, and a swelling agent crosspovidone in different combinations were tried and optimized to get the release profile for 12 hours. The formulations were evaluated for physicochemical characteristics, in vitro drug release profile, swelling characteristics, floating capacity, and in vitro bioadhesive property. in vitro drug release followed the Higuchi kinetics and the release mechanism was found to be of a non-Fickian type. The swelling properties were increased with increasing crosspovidone concentration and contributed to the drug release from the tablet matrix. In this study, an attempt has been made to explore novel effervescent agents such as citroglycine and disodium glycine carbonate for achieving the desired floating time.

Polymer-Based Sustained-Release Dosage Forms for Protein Drugs, Challenges, and Recent Advances

While the concept of using polymer-based sustained-release delivery systems to maintain therapeutic concentration of protein drugs for extended periods of time has been well accepted for decades, there has not been a single product in this category successfully commercialized to date despite clinical and market demands. To achieve successful systems, technical difficulties ranging from protein denaturing during formulation process and the course of prolonged in vivo release, burst release, and incomplete release, to low encapsulation efficiency and formulation complexity have to be simultaneously resolved. Based on this updated understanding, formulation strategies attempting to address these aspects comprehensively were reported in recent years. This review article (with 134 citations) aims to summarize recent studies addressing the issues above, especially those targeting practical industrial solutions. Formulation strategies representative of three areas, microsphere technology using degradable hydrophobic polymers, microspheres made of water soluble polymers, and hydrophilic in vivo gelling systems will be selected and introduced. To better understand the observations and conclusions from different studies for different systems and proteins, physicochemical basis of the technical challenges and the pros and cons of the corresponding formulation methods will be discussed.

Role of TGF-β and FGF in the Treatment of Radiation-Impaired Wounds Using a Novel Drug Delivery System

Despite refinements in radiotherapy, radiation-impaired wound healing continues to be a major source of postoperative morbidity with few treatment options. The application of polypeptide growth factors has been investigated in both the clinical and laboratory settings. The authors used a novel sustained-release delivery system to examine the effect of transforming growth factor (TGF)-beta and fibroblast growth factor (FGF) on radiation-impaired wound healing in a rodent model. Eighty Sprague-Dawley rats underwent dorsal skin surface irradiation of 2500 cGy using a medical linear accelerator producing energy of 6 MeV followed by creation of a full-thickness skin incision. Six groups of 16 animals underwent either sham irradiation (irradiation control); irradiation only; irradiation and unimpregnated delivery system only; or irradiation and either TGF-beta, FGF, or TGF-beta plus FGF combined. Four animals from each group were euthanized at 4, 7, 14, and 28 days, and the harvested specimens underwent ultimate tensile strength testing and histologic evaluation. All five irradiated groups had significantly lower ultimate tensile strength than the sham-irradiated control group at all time points (p < 0.05), thus validating the authors' model of radiation-impaired wound healing. Functional analysis demonstrated that all three growth factor-treated groups had significantly higher tensile strengths than either of the untreated irradiated groups at 14 days after wounding (p < 0.05). Histologic evaluation of the irradiated groups revealed increased cellularity and more organized collagen architecture of all treated groups when compared with the untreated groups, with the most pronounced differences seen at 7 days and 14 days after wounding. This study effectively demonstrates that TGF-beta and FGF act individually and synergistically when delivered locally by means of a sustained release system to improve ultimate tensile strength in an acute postirradiation impaired wound-healing model.

Numerical simulation of drug release from collagen matrices by enzymatic degradation

Biodegradable collagen matrices have become a promising alternative to synthetic polymers as drug delivery systems for sustained release. Previously, a mathematical model describing water penetration, matrix swelling and drug release by diffusion from dense collagen matrices was introduced and tested (cf. Radu et al. in J. Pharm. Sci. 91:964–972, 2002). However, enzymatic matrix degradation influences the drug release as well. Based on experimental studies (cf. Metzmacher in Enzymatic degradation and drug release behavior of dense collagen implants. Ph.D. thesis, LMU University of Munich, 2005), a mathematical model is presented here that describes drug release by collagenolytic matrix degradation. Existence and uniqueness of a solution of the model equations is reviewed. A mixed Raviart–Thomas finite element discretization for solving the coupled system of partial and ordinary differential equations is proposed and analyzed theoretically. The model is verified by a comparison of numerically calculated and experimentally measured data and, in particular, investigated by a parameter sensitivity study. For illustration, some concentration profiles of a two-dimensional simulation are shown.

Increase of the pharmacological and pharmacokinetic efficacy of negatively charged polypeptide recombinant hirudin in rats via parenteral route by association with cationic liposomes

Two biodegradable cationic lipids, stearylamine and DC-Chol, were chosen to investigate the effect of cationic lipids on the in vitro and in vivo characteristics of hydrophilic proteins or peptides of low isoelectric point. Thrombin inhibitor recombinant hirudin variant-2 (rHV2) was selected as the model drug. The cationic lipids were found to achieve higher entrapment efficiency of rHV2 in liposomes than zwitterionic lipids. The positively charged liposomes became less positive and relatively stable in serum after loading rHV2. The cationic liposomes induced sustained release of rHV2 in the presence of plasma, significantly prolonged the antithrombotic efficacy and plasma level of rHV2 after intravenous injection in rats in comparison with neutral lipid liposomes, especially for stearylamine group. Both clotting times correlated well with plasma rHV2 levels. No serious adverse events were observed and physical state of rats was satisfactory for all the formulations. Electrostatic interaction between negative charge of rHV2 and cationic liposomes was confirmed and it might affect all the characteristics of rHV2 loaded cationic vehicles. The findings suggest that cationic liposomes may be a potential sustained-release delivery system for parenteral administration of hydrophilic proteins or peptides with low isoelectric point to prolong efficacy and improve bioavailability.

In vitro and in vivo evaluation of tegaserod maleate pH-dependent tablets

The purpose of this study was to prepare tegaserod maleate (TM) pH-dependent tablets and evaluate their advantages as a sustained release delivery system. TM, insoluble in water and unstable in gastric milieu, was formulated into pH-dependent tablets coated with combinations of two methacrylic acid copolymers - Eudragit L100 and Eudragit S100. The influence of core tablet compositions, polymer combination ratios and coating levels on the in vitro release rate of TM from coated tablets was investigated. The optimum formulation was evaluated for in vitro release rate and in vivo bioavailability study on beagle dogs. In addition, physico-chemical properties of the drug, including solubility at different pH and temperatures, and dissociation constant were determined. The results showed that no drug was released in 0.1 mol/L hydrochloric acid within 2h, and about 90% of the drug was released in the pH 6.8 phosphate buffer within 12h in a sustained manner. The pharmacokinetic investigation showed that TM pH-dependent tablets exhibited a sustained plasma concentration, a lag time of approximately 2.3h and a relative bioavailability of 159% compared to plain tablets. A close correlation existed between the in vitro release rate of the pH-dependent system and its in vivo absorption percentage. The results of the present study have demonstrated that the pH-dependent tablet system is a promising vehicle for preventing rapid hydrolysis in gastric milieu and improving oral bioavailability of TM for the treatment of irritable bowel syndrome.

Implications on Emergence of Antimicrobial Resistance as a Critical Aspect in the Design of Oral Sustained Release Delivery Systems of Antimicrobials

To assess the effects of the unabsorbed fraction of an orally administered antimicrobial drug which enters the colon on the emergence of resistance among the natural microflora, a phenomenon largely overlooked so far despite its clinical importance, especially when sustained release formulations are used. Effects of an orally administered model beta-lactam antibiotic (amoxicillin) on emergence of resistant bacteria were assessed using a microbiological assay for qualitative and quantitative determination of resistant bacteria in fecal samples of rats following gastric administration of the drug to rats for 4 consecutive days. Time- and site-controlled administration of a beta-lactamase to the rat colon was assessed as a potential strategy for prevention the emergence of resistant bacteria following oral administration of incompletely absorbed antimicrobials. Emergence of resistant bacteria was demonstrated following oral administration of amoxicillin to rats, whereas de-activation of the beta-lactam prior to entering the colon, by infusion of a beta-lactamase into the lower ileum, was shown to prevent the emergence of resistant colonic bacteria. This study illustrates the need to consider the emergence of antimicrobial resistance as a goal equally important to microbiological and clinical cure, when designing oral sustained-release delivery systems of antimicrobial drugs.

Effect of drug solubility on release behavior of calcium polysaccharide gel-coated pellets

The aim of this study was to investigate the effect of drug solubility on the release behavior from calcium polysaccharide gel (CaPG)-coated pellets. Three different drugs with similar chemical structure, but different water solubility, namely caffeine (CAF), theophylline (TPL) and theobromine (TBR), were used. Drug-loaded spherical pellets were manufactured by an extrusion–spheronization method. The CaPG was applied on the pellets loaded with different drugs by interfacial complexation coating. The encapsulation efficiency of coated pellets was found to vary from 57.6 to 84.3%, depending on the solubility of the active drug and polysaccharide type. Drug release from different uncoated pellets was relatively unaffected by pH and release media but depended mainly on drug solubility. Release behavior was significantly modified in the pellets coated with CaPG, for all of the drugs tested. Drug release from coated pellets of the different drugs showed different release kinetics. The difference in the drug release is probably due to the difference in the drug dissolution within the core, before its partition and diffusion through the CaPG coat. The CAF dissolved faster and achieved a higher concentration in solution, which drove diffusion. The release of TBR from the coated pellets was much slower than that of the CAF or TPL because of its low solubility. However, the release of all drugs was about four- to sixfold slower for coated than uncoated pellets, suggesting that the coating influenced the retardation of drug release from the coated pellets. Therefore, the CaPG coating may provide a sustained release delivery system for all drugs tested.

In vivo evaluation of risperidone-SAIB in situ system as a sustained release delivery system in rats

The objective of this study was to evaluate a sustained release sucrose acetate isobutyrate (SAIB) in situ system formulation of risperidone (RSP) in vivo. The formulation contained SAIB, ethanol, and polylactic acid (PLA) as a release regulator. In vivo pharmacokinetics (PK) studies have shown that PLA is effective in reducing the burst effect. After a 12.5 mg/kg IM injection of a 25 mg/g RSP-SAIB in situ system, the C max was markedly reduced from 944.1 ± 80.2 to 330.4 ± 33.6 ng/ml by increasing PLA from 1% to 10% (w/w), the T max were prolonged from 2 to 4.3 ± 2.0 h, and the area under the curve from day 0 to 2 (AUC 0–2 day ) was reduced significantly from 16294.8 ± 3946.4 to 7025.3 ± 1979.2 ng h/ml. For the RSP-SAIB in situ system including 10% PLA, the high release rates over a short period allowed therapeutic plasma concentrations to be achieved in the initial stages after activation, and sustained release of the drug led to a stable plasma concentration (by day 25, the plasma concentration was 8% of the C max). These initial in vivo studies suggest that RSP-SAIB in situ system is effective as a sustained delivery system.

A lipid-based liquid crystalline matrix that provides sustained release and enhanced oral bioavailability for a model poorly water soluble drug in rats

Liquid crystalline phases that are stable in excess water, formed using lipids such as glyceryl monooleate (GMO) and oleyl glycerate (OG), are known to provide a sustained release matrix for poorly water soluble drugs in vitro, yet there has been no report of the use of these materials to impart oral sustained release behaviour in vivo. In the first part of this study, in vitro lipolysis experiments were used to compare the digestibility of GMO with a second structurally related lipid, oleyl glycerate, which was found to be less susceptible to hydrolysis by pancreatic lipase than GMO. Subsequent oral bioavailability studies were conducted in rats, in which a model poorly water soluble drug, cinnarizine (CIN), was administered orally as an aqueous suspension, or as a solution in GMO or OG. In the first bioavailability study, plasma samples were taken over a 30 h period and CIN concentrations determined by HPLC. Plasma CIN concentrations after administration in the GMO formulation were only sustained for a few hours after administration while for the OG formulation, the plasma concentration of cinnarizine was at its highest level 30 h after dosing, and appeared to be increasing. A second study in which CIN was again administered in OG, and plasma samples taken for 120 h, revealed a T max for CIN in rats of 36 h and a relative oral bioavailability of 344% when compared to the GMO formulation (117%) and the aqueous suspension formulation (assigned a nominal bioavailability of 100%). The results indicate that lipids that form liquid crystalline structures in excess water, may have application as an oral sustained release delivery system, providing they are not digested rapidly on administration.

In vitro and in vivo evaluation of donepezil-sustained release microparticles for the treatment of Alzheimer's disease

The purpose of this work is to prepare donepezil microparticles (DM) and evaluate its advantage as a sustained release delivery system with subcutaneous injection once a month. DM was prepared using poly ( d,l-lactide- co-glycolide) (PLGA) by an oil-water emulsion solvent evaporation technique. DM showed the loading ratio 13.2±2.1% (w/w) and yield 54.8±0.8% with mean particle size about 75 μm. In vitro release of DM showed that donepezil completely released within 28 days in water, but the cumulative release percentages up to day 30 were 98.4% and 49.1% for phosphate buffer saline (PBS, pH 5.8) and PBS (pH 7.4), respectively. The in vivo experiment demonstrated that DM (90 mg/kg) produced a sustained release process in rats, and reached steady-state concentration at day 8 and maintained until day 27 with steady-state levels of donepezil between 130.3±7.8 and 121±9.8 ng/ml, which was accordance with that of free donepezil by oral application route (3 mg/kg day). DM (90 mg/kg) by subcutaneous infusion in rats produced the same pharmacological role as free donepezil (3 mg/kg day) by oral application route. These results implicated that DM as a sustained release delivery strategy could substitute for its oral formulation for therapy of AD and come true its administration once a month.

Multiple dosage forms of the NNRTI microbicide dapivirine: product development and evaluation

The disproportionate impact of the expanding AIDS epidemic in women of the developing world clearly establishes the need for anti-HIV microbicides. Although semi-solid gels were the conventional dosage form developed for early microbicides, newer acceptability data and studies from the contraceptive field have demonstrated the need for additional alternative dosage forms that are acceptable to the relevant target populations. Reducing the burden of user compliance is equally critical in the next generation of products. Our development efforts with the highly potent NNRTI microbicide dapivirine have involved multiple dosage forms, with the objective of decoupling product use from sexual intercourse. Once per day gels and tablets are being developed, as are intravaginal ring delivery systems for sustained release. Preclinical development studies, formulation development and characterization, and clinical evaluations of these alternative drug product forms will be discussed. Our findings suggest that potent anti-retroviral compounds can be safely configured for acceptable dosing in women, and that these drugs and delivery strategies can be successfully applied in microbicide development.

Pharmacokinetics and Pharmacodynamics of Lipidic Nano-Particles in Cancer

Nanoscale drug delivery systems (DDS) are used to circumvent some of the non-ideal properties of conventional anticancer chemotherapy drugs. Manipulation of the physical properties of DDS provides improved control over the pharmacokinetics (PK) and pharmacodynamics (PD) of the encapsulated drugs relative to free drugs. Liposomes are the archetypical nanoscale DDS and the first of these received clinical approval in 1990. DOXIL, liposomal doxorubicin, was the first commercially available liposomal anticancer drug (1995). It has an enhanced circulation half-life compared to the free drug because of its surface-grafted polyethylene glycol coating. DOXIL passively targets solid tumors, and once the liposomes localize in the tumor interstitial space, the cytotoxic drug is slowly released within the tumor. Liposomes can act as sustained release delivery system and manipulation of properties such as, liposome diameter, drug release rate, bioavailability and dosing schedule can significantly impact the therapeutic outcome of the liposomal drugs. This review will focus on how alteration of these properties can impact the therapeutic efficacy and side effect profiles of DDS.

Characterization, bioactivity and ampicillin release kinetics of TiO2 and TiO24SiO2 synthesized by sol-gel processing

Local drug delivery of antimicrobics by sustained release delivery system can be used to treat periodontal disease. Advantages of these systems may include maintaining high levels of antibiotic in the gingival crevicular fluid for a sustained period of time and ease of use with high patient acceptance. The materials used are TiO(2) and TiO(2)4SiO(2), mixed with sodium ampicillin, a broad-spectrum antibiotic, have been synthesized by sol-gel method. The amorphous nature of the gels was ascertained by X-ray diffraction analysis. Release kinetics in a simulated body fluid (SBF) have been subsequently investigated. The amount of sodium ampicillin released has been detected by UV-VIS spectroscopy and SEM. The release kinetics seems to occur in more than one stage. HPLC analysis has also been taken to ensure the integrity of ampicillin after the synthetic treatment. Finally, SEM micrographs and EDS analysis showed the formation of a hydroxyapatite layer on the surface of the samples soaked in SBF. Both the materials showed good release and could be used as drug delivery bioactive systems. High antimicrobial effects of samples against Escherichia coli and Streptococcus mutants were found.

Novel sustained release, swellable and bioadhesive gastroretentive drug delivery system for ofloxacin

Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new gastroretentive sustained release delivery system was developed with floating, swellable and bioadhesive properties. All these properties were optimized and evaluated. Various release retarding polymers like psyllium husk, HPMC K100M and a swelling agent, crosspovidone in combinations were tried and optimized to get the release profile for 24 h. Formulations were evaluated for in vitro drug release profile, swelling characteristics and in vitro bioadhesion property. The in vitro drug release followed Higuchi kinetics and the drug release mechanism was found to be of anomalous or non-Fickian type. For the developed formulation, the value of n was found to be 0.5766 while for the marketed formulation the value was 0.5718 indicating the anomalous transport. The high water uptake leading to higher swelling of the tablet supported the anomalous release mechanism of ofloxacin. The similarity factor f2 was found to be 91.12 for the developed formulation indicating the release was similar to that of the marketed formulation (Zanocin OD). The swelling properties were increased with increasing crosspovidone concentration and contributed significantly in drug release from the tablet matrix. The bioadhesive property of the developed formulation was found to be significant ( P < 0.005) in combination as compared to HPMC K100M and psyllium husk alone.

미세 다공성 과립을 이용한 탐스로신의 방출제어

Tamsulosin or a salt thereof such as its hydrochloride salt has been known to have an adrenaline receptor blocking action for urethra and prostate areas. It has been widely used as a drug which lowers the prostate pressure and improves urinary disturbance accompanied by prostate-grand enlargement, thus for the treatment of prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is essentially required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin granules and assess their formulation variables. We designed entric coated sustained-release tamsulosin granules for this purpose. Nano-pores in the outer controlled release membrane were needed in order to obtain initial tamsulosin release even in an acidic environment such as gastric region. In our sustained release osmotic granule system, hydroxypropylmethylcellulose in a drug-containing layer was used as a rate controller. The drug-containing granules were coated with hydroxypropylmethylcellulose phthalate (HPMCP) and Eudragit, along with glycerol triacetate as an aqueous nano-pore former. The release of tamsulosin depended heavily on the type of Eudragit such as RS, RL, NE 30D, used in the formulation of controlled release layer. These results obtained clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the Korean Food and Drug Administration.

Pegylated Protein Encapsulated Multivesicular Liposomes: A Novel Approach for Sustained Release of Interferon α

Hepatitis C viral chemotherapy suffers from a relatively short half-life of the interferon α-2a (IFN α). To address this issue, we investigated the effects of polyethylene glycol modification and their subsequent encapsulation in multivesicular liposomes (MVLs), on the release properties of IFN α. In the present study, interferon-α was conjugated with methoxy-polyethylene glycol (mPEG, MW 5000). Prepared IFN α-mPEG5000 conjugate (IFN α-mPEG5000) was purified with size exclusion chromatography. The relative in vitro anti-viral activity of pegylated interferon α-2a was found to 87.9% of the unmodified IFN α. Pegylated IFN α encapsulated multivesicular liposomes were prepared by double emulsification technique followed by evaporation of organic solvents from chloroform ether spherules suspended in water. Prepared MVLs were then characterized for shape, size, vesicle count, encapsulation efficiency, and in vitro release rate. In process stability studies of pegylated IFN α protein exhibited better stability when exposed to chloroform: diethyl ether (1:1 ratio) mixture as well as variable vortexing time as compared to native IFN α. Relatively high percentage of encapsulation of protein (∼75%) was achieved. In vitro release profile of pegylated IFN α-mPEG5000 containing MVLs in the PBS showed lower initial burst release with sustained and incomplete release over a period of 1 week. In contrast, native IFN α entrapped MVLs were observed as higher initial burst release, i.e., nearly 35% followed by almost complete release. The results confirmed the possibility of multivesicular liposomes as a long-acting or sustained-release delivery system using a combination of pegylation and encapsulation technique for controlled delivery of interferon α.

Sustained‐release delivery systems of triclosan for treatment of Streptococcus mutans biofilm

Dental diseases are chronic infections caused by oral bacteria harboring the dental biofilm. Local sustained-release delivery systems prolong the duration of a drug in the oral cavity, thus enhancing its therapeutic potential, while reducing its side effects. Triclosan is an agent that was found to have an antibacterial effect against oral bacteria. However, its substantivity in the oral cavity is low, resulting in reduced antibacterial efficiency. The purpose of this study was to develop a local sustained release device containing triclosan and to test its antibacterial efficacy on Streptococcus mutans biofilm. Our results show that we can formulate an ethylcellulose-based, nondegradable, sustained-release device in which 80% of the loaded triclosan is released over a 10-day period. The release rate of triclosan corresponded to the Higuchi's planar homogenous diffusion release model (r2 = 0.998). A degradable local sustained-release delivery based on a methacrylate ester matrix was also developed for a faster release rate of triclosan. The release kinetics in those types of sustained-release delivery systems was erosion control. The local sustained-release delivery system significantly affected the viability of S. mutans in biofilm compared to placebo as was tested by confocal laser scanning microscopy. Our in vitro results show that triclosan can be incorporated into degradable or nondegradable sustained-release drug delivery systems. The release of triclosan from the local sustained-release delivery system can be controlled, thus extending its antibacterial properties.