Dendrimers are hyperbranched nanoparticle structures along with its surface modifications can to be used in dental biomaterials for biomimetic remineralisation of enamel and dentin. The review highlights the therapeutic applications of dendrimers in the field of dentistry. It addresses the possible mechanisms of enhancement of mechanical properties of adhesives and resins structure. Dendrimers due to its unique construction of possessing inner hydrophobic and outer hydrophilic structure can act as drug carrier for delivery of antimicrobial drugs for treatment of periodontal diseases and at peripheral dental implant areas. Dendrimers due to its hyperbranched structures can provides a unique drug delivery vehicle for delivery of a drug at specific site for sustained release for therapeutic effects. Thus, dendrimers can be one of the most important constituents which can be incorporated in dental biomaterials for better outcomes in dentistry.
Olopatadine HCl is an antiallergic drug used for the management of allergic conjunctivitis. Currently, it is delivered via eye drop solution, which is highly inefficient due to low bioavailability. Silicone contact lenses can be used to sustain the release of ophthalmic drugs. However, the presence of drug alters the optical transmittance and physical properties of the contact lens. The objective was to design a novel polyvinyl pyrrolidone (PVP)-coated olopatadine-ethyl cellulose microparticles-laden doughnut contact lens to sustained ocular delivery with limited alteration to the optical and swelling properties of the contact lens. The doughnut was implanted within the periphery of the lens using modified casting technique. Olopatadine HCl was loaded by soaking (SM-OL), direct loading (DL-OL), and doughnut casting method (DNT-OL). PVP (comfort agent) was loaded on the surface of contact lens for all the batches via novel curing technique. The in vitro olopatadine HCl release data of SM-OL (up to 48-72 h) and DL-OL batches (up to 72 h) showed high burst release, whereas DNT-OL batch showed sustained release up to 120 h without significant (p > 0.05) alteration in the optical and swelling properties of contact lens. All the batches showed sustained release of PVP up to 120 h. The in vivo studies in the rabbit tear fluid showed improvement in the olopatadine HCl and PVP retention time in comparison to eye drop solution. The PVP-loaded DNT-OL-500 lens showed tear stabilization (comfort wear) in Schirmer strip test (rabbits) with no protein adherence in comparison to DNT-OL-500 lens without PVP. The study demonstrated the successful delivery of olopatadine HCl and PVP-K30 from the doughnut contact lens for the extended period with limited alteration to the optical and swelling properties of contact lens.
The world does not have too much time to ensure that the fast-growing population has enough land, food, water and energy. The rising food demand has brought a positive surge in fertilizers' demand and agriculture-based economy. The world is using 170 million tons of fertilizer every year for food, fuel, fiber, and feed. The nitrogenous fertilizers are being used to meet 48% of the total food demand of the world. High fertilizer inputs augment the reactive nitrogen levels in soil, air, and water. The unassimilated reactive nitrogen changes into a pollutant and harms the natural resources. The use of controlled-release fertilizers for slowing down the nutrients' leaching has recently been practiced by farmers. However, to date, monitoring of the complete discharge time and discharge rate of controlled released fertilizers is not completely understood by the researchers. In this work, corn starch was thermally processed into a week gel-like coating material by reacting with urea and borate. The granular urea was coated with native and processed starch in a fluidized bed reactor having bottom-up fluid delivery system. The processed starch exhibited better thermal and mechanical stability as compared to the native starch. Unlike the pure starch, the storage modulus of the processed starch dominated the loss modulus. The release time of urea, coated with processed starch, remained remarkably larger than the uncoated urea.
Black seed oil (BSO) has been used for various therapeutic purposes around the world since ancient eras. It is one of the most prominent oils used in nutraceutical formulations and daily consumption for its significant therapeutic value is common phenomena. The main aim of this study was to develop alginate-BSO beads as a controlled release system designed to control drug release in the gastrointestinal tract (GIT). Electrospray technology facilitates formulation of small and uniform beads with higher diffusion and swelling rates resulting in process performance improvement. The effect of different formulation and process variables was evaluated on the internal and external bead morphology, size, shape, encapsulation efficiency, swelling rate, in vitro drug release, release mechanism, ex vivo mucoadhesive strength and gastrointestinal tract qualitative and quantitative distribution. All the formulated beads showed small sizes of 0.58 ± 0.01 mm (F8) and spherical shape of 0.03 ± 0.00 mm. The coefficient of weight variation (%) ranged from 1.37 (F8) to 3.93 (F5) ng. All formulations (F1-F9) were studied in vitro for release characteristics and swelling behaviour, then the release data were fitted to various equations to determine the exponent (ns), swelling kinetic constant (ks), swelling rate (%/h), correlation coefficient (r2) and release kinetic mechanism. The oil encapsulation efficiency was almost complete at 90.13% ± 0.93% in dried beads. The maximum bead swelling rate showed 982.23 (F8, r2 = 0.996) in pH 6.8 and the drug release exceeded 90% in simulated gastrointestinal fluid (pH 6.8). Moreover, the beads were well distributed throughout various parts of the intestine. This designed formulation could possibly be advantageous in terms of increased bioavailability and targeted drug delivery to the intestine region and thus may find applications in some diseases like irritable bowel syndrome.
Multi-particulate Dome matrix with sustained-release melatonin and delayed-release caffeine was designed to restore jet lag sleep-wake cycle. The polymeric pellets were produced using extrusion-spheronization technique and fluid-bed coated when applicable. The compact and Dome module were produced by compressing pellets with cushioning agent. Dome matrix was assembly of modules with pre-determined compact formulation and drug release characteristics. The physicochemical and in vivo pharmacokinetics of delivery systems were examined. Melatonin loaded alginate/chitosan-less matrix exhibited full drug release within 8 h gastrointestinal transit with low viscosity hydroxypropymethylcellulose as cushioning agent. The cushioning agent reduced burst drug release and omission of alginate-chitosan enabled full drug release. Delayed-release alginate-chitosan caffeine matrix was not attainable through polymer coating due to premature coat detachment. Admixing of cushioning agent high viscosity hydroxypropylmethylcellulose and high viscosity ethylcellulose (9:1 wt ratio) with coat-free caffeine loaded particulates introduced delayed-release response via hydroxypropylmethylcellulose swelled in early dissolution phase and ethylcellulose sustained matrix hydrophobicity at prolonged phase. The caffeine was released substantially in colonic fluid in response to matrix polymers being degraded by rat colonic content. Dome matrix with dual drug release kinetics and modulated pharmacokinetics is produced to introduce melatonin-induced sleep phase then caffeine-stimulated wake phase.
Cell- based targeted delivery is recently gain attention as a promising platform for delivery of anticancer drug in selective and efficient manner. As a new biotechnology platform, bacterial ghosts (BGs) have novel biomedical application as targeted drug delivery system (TDDS). In the current work, Salmonellas' BGs was utilized for the first time as hepatocellular cancer (HCC) in-vitro targeted delivery system. Successful BGs loading and accurate analysis of doxorubicin (DOX) were necessary steps for testing the applicability of DOX loaded BGs in targeting the liver cancer cells. Loading capacity was maximized to reach 27.5 µg/mg (27.5% encapsulation efficiency), by incubation of 10 mg BGs with 1 mg DOX at pH 9 in constant temperature (25 °C) for 10 min. In-vitro release study of DOX loaded BGs showed a sustained release (182 h) obeying Higuchi sustained kinetic release model. The death rate (tested by MTT assay) of HepG2 reached to 64.5% by using of 4 μg/ml, while it was about 51% using the same concentration of the free DOX (P value
Low bioavailability and poor water solubility have limited the utilization of curcumin in conventional dosing methods. As an alternative, microemulsions as drug carrier can improve curcumin delivery. A cetyltrimethylammonium bromide-nanocrystalline cellulose (CTAB-NCC)-based microemulsion was developed and its potential use as a topical delivery method for curcumin was investigated. The effect of microemulsion's particle size and its microstructure as well as the presence of the CTAB-NCC nanoparticle on the topical delivery of curcumin was studied. In vitro permeation studies showed higher penetration rate of curcumin from the oil-in-water type-microemulsions. The skin permeation profile of curcumin followed Higuchi release kinetics. Furthermore, use of the (CTAB-NCC)-based microemulsion enhanced curcumin accumulation in the skin and these system showed non cytotoxicity effect on L929 cell line. These results showed the potential of (CTAB-NCC)-based microemulsions as controlled-release topical systems for the delivery of curcumin and potentially other lipophilic drugs.
The acrylated palm oil (APO) nanoparticle is a potential product that can be used as carriers in
medical field. The main focus of the present study was to study the potential of the APO
nanoparticles for used in a controlled drug delivery system. The microemulsion system is used as a
medium to incorporate an active substance such as Thymoquinone (TQ) into the APO polymeric
micelle and then the radiation technique is used as a tool for the synthesis of TQ-loaded APO
nanoparticle. The nano-size TQ-loaded APO particles resulted the particle size of less than 150 nm
with spherical in shape. The TQ release profile was carried out in potassium buffer saline (PBS)
solutions (pH 7.4) at 37
oC. And, the zero-order model has been used to determine the mechanism
of the drug release from the corresponding nanoparticles, respectively. The TQ release was found
to be sustained and controlled in pH 7.4. At pH 7.4, the release of TQ followed the zero-order
model. The in-vitro drug release study showed a good prospect of the APO nanoparticle on being a
potential drug carrier as there are toxic against colon cancer cells and not toxic towards normal
cells. This suggested that the APO product produce using this radiation technique can be
developed into different type of carrier systems for controlled drug release applications.
PIP: To determine the acceptability, practicability, and popularity of Depo-Provera as an additional contraceptive method to be offered by the National Family Planning Board NFPB of Malaysia, 550 patients of Sungai Besar, Malaysia, who accepted the Depo-Provera injection method from the start of the injection program, February 23, 1968, until the cutoff date of December 31, 1969, were studied. At the cutoff date, 318 (58%) were still receiving regular injections at 3-month intervals. The remaining 232 women discontinued use of the injection. Of those who discontinued use, 176 (32%) were interviewed, while the other 56 women were lost to follow-up, due mainly to migration. Assuming that 1 injection would protect a woman from getting pregnant for a 3-month period, the retention rates at the end of 12 and 24 months were 63% and 41%. These continuation rates were fairly high and were as good as those for the oral pill, which is the main contraceptive method provided since the beginning of the operational service program of the NFPB in May 1967. Except for a small number of Indian women with a high rate of discontinuation there was not much difference in continuing the method between the Malays (60%) and the Chinese (56%). The younger age group of women seemed to have a higher proportion of discontinuation. The findings showed that amenorrhea (35%)most bothered the women who discontinued the injection method. Irregular bleeding (20%) and other medical side effects (11%) were the other main complaints that caused women to discontinue using the injection as a contraceptive method. It was concluded that Depo-Provera (150 mg) injected once every 3 months appears to be simple, acceptable, popular, and effective as a contraceptive method among women in a rural town in Malaysia.
Age-related macular degeneration (AMD), a degenerative eye disease, is the major cause of irreversible loss of vision among individuals aged 50 and older. Both genetic and environmental factors are responsible for the progressive damage to central vision. It is a multifactorial retinal disease with features such as drusen, hypopigmentation and/or hyperpigmentation of the retinal pigment epithelium, and even choroidal neovascularization in certain patients. AMD is of two major forms: exudative (wet) and atrophic (dry) with changes affecting the macula leading to impaired vision. Although the retina remains an accessible portion for delivering drugs, there are no current options to cure or treat AMD. The existing expensive therapeutics are unable to treat the underlying pathology but display several side effects. However, recent innovations in nanotherapeutics provide an optimal alternative of drug delivery to treat the neovascular condition. These new-age technologies in the nanometer scale would enhance bioactivity and improve the bioavailability of drugs at the site of action to treat AMD. The nanomedicine also provides sustained release of the drug with prolonged retention after penetrating across the ocular tissues. In this review, the insights into the cellular and molecular mechanisms associated with the pathophysiology of AMD are provided. It also serves to review the current progress in nanoparticle-based drug delivery systems that offer feasible treatments in AMD.
Obesity is one of the most important problems worldwide. Khat (Catha edulis), an evergreen shrub, is thought to reduce body-weight. Its effect is more prominent when khat leaves are chewed. Thus, anti-obesity effects of khat and its associated side effects may depend on the release rate of its active constituents. The present study aimed to investigate the effect of a selected low dose of dried-khat, extracted, formulated as controlled release delivery systems on the body weight (BW), food intake (FI), cholesterol (CS) and triglyceride (TG) levels in rats. Khat extract (KE) was microencapsulated (KE235) and formulated into a parenteral implant (InjKE235). The effects of KE, KE235 and InjKE235 on BW, FI, CS and TG in rats were investigated. The results showed that microcapsules sustained the khat alkaloid release with T50% 1.58 h for KE235 and 14.41 days for InjKE235. KE and KE235 caused maximum reduction in BW, FI, CS and TG during the first to third weeks but rebound gradually thereafter. On the contrary, InjKE235 exhibited a sustained reduction in BW, FI, CS and TG levels for 2 months. The T50% of KE, KE235 and InjKE235 correlated with the reduction in BW, CS and TG but not with FI. In conclusion, the subcutaneous injection and sustained release rate of khat extract play an important role in enhancing the anti-obesity effect in SD rats.:
The aim of the present work was to investigate the preparation of microspheres as potential drug carriers for proteins, intended for controlled release formulation. The hydrophilic bovine serum albumin was chosen as a model protein to be encapsulated within poly(D,L-lactide-co-glycolide) (50:50) microspheres using a w/o/w double emulsion solvent evaporation method. Different parameters influencing the particle size, entrapment efficiency and in vitro release profiles were investigated. The microspheres prepared with different molecular weight and hydrophilicity of poly(D,L-lactide-co-glycolide) polymers were non porous, smooth surfaced and spherical in structure under scanning electron microscope with a mean particle size ranging from 3.98 to 8.74 mum. The protein loading efficiency varied from 40 to 71% of the theoretical amount incorporated. The in vitro release profile of bovine serum albumin from microspheres presented two phases, initial burst release phase due to the protein adsorbed on the microsphere surface, followed by slower and continuous release phase corresponding to the protein entrapped in polymer matrix. The release rate was fairly constant after an initial burst release. Consequently, these microspheres can be proposed as new controlled release protein delivery system.
The predilection of a bi-layered tablet to fail in the interface region after its initial formation in the compaction process reduces its practicality as a choice for controlled release solid drug delivery system. Hence, a fundamental appreciation of the governing mechanism that causes the weakening of the interfacial bonds within the bi-layered tablet is crucial in order to improve the overall bi-layered tablet mechanical integrity. This work has shown that the occurrence of the elastic relaxation in the interface region during the ejection stage of the compaction process decreases with the increase in the bi-layered tablet interface strength. This is believed to be due to the increase in the plastic bonding in the interface region. The tablet diametrical elastic relaxation affects the tablet height elastic relaxation, where the impediment of the tablet height expansion is observed when the interface region experiences a diametrical expansion.
The effect of urea-loaded cellulose hydrogel, a controlled-release fertilizer (CRF) on growth and yield of upland rice were investigated in upland rice. As with the initial research, nitrogen (N) treatments were applied as CRF treatments; T2H (30 kg N ha-1), T3H (60 kg N ha-1), T4H (90 kg N ha-1), T5H (120 kg N ha-1) and recommended dose of fertilizer (RDF) at 120 kg N ha-1 RDF (T6U) in split application and T1 (0 N) as control. Results from this study indicated that applying CRF at the optimum N rate, T4H resulted in maximum grain yield, increasing by 71%. The analysis of yield components revealed that higher grain yield in T4H CRF was associated with an increase in panicle number and number of grains per panicle. Maximum grain N uptake of 0.25 g kg-1 was also observed in T4H CRF. In addition, T4H CRF recorded the highest harvest index (HI) and N harvest index (NHI) of 45.5% and 67.9%, respectively. Application of T4H CRF also recorded the highest N use efficiency (NUE) and N agronomic efficiency (NAE), 52.6% and 12.8 kg kg-1, respectively. Observations show that CRF with only 75% N applied (T4H) in soil improved grain yield when compared to CRF with 100% N and 100% RDF in farmers' conventional split application. This suggested that CRF with a moderate N application might produce the highest potential yield and improved N efficiencies while enhancing crop production and further increase in N supply did not increase yield and N efficiencies. The results suggest that the application of T4H CRF for upland rice would enhance HI, N efficiencies and improve the yield of upland rice. Also, all growth parameters and yield were positively influenced by the application of CRF as a basal dose compared to split application of conventional urea fertilizers.
The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.
Drug delivery systems are designed to achieve drug therapeutic index and enhance the efficacy of controlled drug release targeting with specificity and selectivity by successful delivery of therapeutic agents at the desired sites without affecting the non-diseased neighbouring cells or tissues. In this research, we developed and demonstrated a bio-based calcium carbonate nanocrystals carrier that can be loaded with anticancer drug and selectively deliver it to cancer cells with high specificity by achieving the effective osteosarcoma cancer cell death without inducing specific toxicity. The results showed pH sensitivity of the controlled release characteristics of the drug at normal physiological pH 7.4 with approximately 80% released within 1,200 min but when exposed pH 4.8 the corresponding 80% was released in 50 min. This study showed that the DOX-loaded CaCO₃ nanocrystals have promising applications in delivery of anticancer drugs.
A controlled release formulation for the insect pheromone hexenoic acid (HE) was successfully developed using zinc-layered hydroxide (ZLH) as host material through a simple coprecipitation technique, resulting in the formation of inorganic-organic nanolayered material with sustained release properties. The release of HE from its nanohybrid was found to occur in a controlled manner, governed by a pseudo-second order kinetics model. The maximum amount of HE released from the nanocomposite into solutions at pH 4, 6.5, and 8 was found to be 84, 73, and 83% for 1100 min, respectively. The hexenoate zinc-layered hydroxide nanomaterial (HEN) was found to be nontoxic for plants when green beans and wheat seeds were successfully germinated in all HEN concentrations tested in the experiment, with higher percentage of seed germination and higher radical seed growth as compared to its counter anion, HE. ZLH can be a promising carrier for insect pheromone toward a new generation of environmentally safe pesticide nanomaterial for crop protection.
Topical chemotherapy is the application of cancer drugs directly onto the skin, which has become a standard treatment for basal cell carcinoma. Due to the promising results in the treatment of skin cancer, topical chemotherapy has recently been applied to breast cancer patients because some breast cancer tissues are only superficial. Hydroxytyrosol, a phenolic compound from olives that is present in high amounts in Hidrox(®) olive extract, has been shown to have a protective effect on normal cells and selective antitumor activities on cancerous cells. The aims of the present study were to develop an alginate bilayer film containing Hidrox(®) and to investigate its potential use as a topical chemotherapeutic agent. Alginate films were characterized for swelling and for physical, thermal, rheological, and mechanical properties. Drug content uniformity and in vitro drug release tests were also investigated. The alginate bilayer films containing Hidrox(®), HB2, showed controlled release of hydroxytyrosol at a flux of 0.094±0.009 mg/cm(2)/h. The results of the cytotoxic assay showed that the HB2 films were dose-dependent and could significantly reduce the growth of breast cancer cells (MCF-7) at 150 μg/mL for a cell viability of 29.34±4.64%. In conclusion, an alginate bilayer film containing Hidrox(®) can be a potential alternative for topical chemotherapeutic agent for skin and breast cancer treatment.
Gastroesophageal reflux disease (GERD) is the most common disorder with a significantly high global prevalence. Prokinetic drugs are commonly recommended for the treatment of gastric reflux, in addition to antacids and antisecretory agents. Itopride hydrochloride, a prokinetic agent, acts as a D2 receptor antagonist and an acetylcholinesterase inhibitor, improving GERD symptoms. The objective of this study was to develop a floating-type gastroretentive drug delivery system, which was further evaluated by in vitro and in vivo studies. Itopride hydrochloride-loaded gastroretentive pellets were prepared using pelletization followed by spheronization. The preparation of itopride-loaded gastroretentive pellets was optimized using a central composite experimental design (32), varying the concentrations of ethylcellulose and Eudragit S100 as independent variables, while floating time and percentage of drug release were considered dependent variables.The optimized batch was characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR). It was then evaluated for mucoadhesion, in vivo gastric retention, and bioavailability in rabbits. The in vitro drug release from the optimized pellet formulation exhibited approximately 97.84% release over 10 h and maintained buoyancy for up to 9 h. In vivo gastric residence time was observed to be 6 h, with a bioavailability of 52.87 ± 0.15 µg/mL/h. Based on in vitro and in vivo findings, the developed gastroretentive mucoadhesive pellet formulation presents a promising drug delivery system for the treatment of GERD, potentially enhancing drug efficacy through prolonged gastric retention.
Modulation of initial burst and long term release from electrospun fibrous mats can be achieved by sandwiching the drug loaded mats between hydrophobic layers of fibrous polycaprolactone (PCL). Ibuprofen (IBU) loaded PCL fibrous mats (12% PCL-IBU) were sandwiched between fibrous polycaprolactone layers during the process of electrospinning, by varying the polymer concentrations (10% (w/v), 12% (w/v)) and volume of coat (1 ml, 2 ml) in flanking layers. Consequently, 12% PCL-IBU (without sandwich layer) showed burst release of 66.43% on day 1 and cumulative release (%) of 86.08% at the end of 62 days. Whereas, sandwich groups, especially 12% PCLSW-1 & 2 (sandwich layers-1 ml and 2 ml of 12% PCL) showed controlled initial burst and cumulative (%) release compared to 12% PCL-IBU. Moreover, crystallinity (%) and hydrophobicity of the sandwich models imparted control on ibuprofen release from fibrous mats. Further, assay for cytotoxicity and scanning electron microscopic images of cell seeded mats after 5 days showed the mats were not cytotoxic. Nuclear Magnetic Resonance spectroscopic analysis revealed weak interaction between ibuprofen and PCL in nanofibers which favors the release of ibuprofen. These data imply that concentration and volume of coat in flanking layer imparts tighter control on initial burst and long term release of ibuprofen.