Sustained Drug Delivery System Research Articles

Sustained drug delivery system takes lung disease treatment to the next level

Sustained drug delivery system takes lung disease treatment to the next level

RECENT ADVANCEMENT AND CHALLENGES IN BILAYER TABLET TECHNOLOGY: AN OVERVIEW

Bilayer tablets were developed recently for the effective production of controlled release formulations in various quality levels to give a method of successful drug delivery. Over the last three decades, as the cost and complexity of developing novel pharmacological entities have increased and as the therapeutic benefits of controlled drug administration have been recognized, considerable attention has been focused on developing sustained or controlled release drug delivery systems. It is utilized to produce a variety of antihypertensive formulations. Bilayer tablets allow for the predetermined release of two drugs in combination, separating two incompatible substances, and sustained-release tablets with one layer serving as the loading dose and the second layer serving as the maintenance dose. Bilayer tablets are advancing helpful technologies to overcome the disadvantages of single-layered tablets. However, bilayer tablet technology is resource-intensive. A thorough selection of excipients and manufacturing conditions for each technical stage is also required. The purpose of this paper is to summarize the state of art in bilayer tablet technology and to highlight the difficulties encountered during bilayer tablet manufacture, as well as the possible solutions for these obstacles. KEYWORDS: Bilayer tablet, Conventional release, Controlled release, Sustained release, Maintenance dose

A sustainable nano drug delivery system for poorly soluble drug, glipizide: design, in vitro controlled release and kinetics

The present work deals with the design of drug delivery systems based on 12-tungstophosphoric acid (TPA)-functionalized MCM-48 nanoparticles (TPA/nMCM-48), for poorly soluble drug GLP.

Capsanthin-Loaded Micelles: Preparation, Characterization and in vitro Evaluation of Cytotoxicity Using MDA-MB-231 Breast Cancer Cell Line.

Breast cancer is one of the most common cancers and remains a major cause of morbidity and mortality among women worldwide. In developed countries, breast cancer as a multifactorial disease is a major health concern, and its incidence is constantly rising in low and middle-income countries. Numerous studies have demonstrated that phytochemicals such as carotenoids inhibit breast cancer growth and induce apoptosis. We recently enhanced the solubility of capsanthin in water by encapsulating it in diosgenin polyethylene glycol succinate, a novel non-ionic surfactant. Thus, this study aims to evaluate the cytotoxicity of water-soluble capsanthin-loaded micelles in MDA-MB-231 cells in vitro through tetrazolium dye MTT assay. In the current study, capsanthin, a hydrophobic carotenoid, is extracted from sweet red pepper (Capsicum annuum). Capsanthin-loaded diosgenin polyethylene glycol succinate 1000 (cap-DPGS-1000) micelles were prepared from capsanthin extract (cap) and diosgenin polyethylene glycol succinate 1000 (DPGS-1000) using the solid dispersion method. The capsanthin extract and cap-DPGS-1000 micelles were characterized by UV-visible spectroscopy, high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size distribution, polydispersity, and scanning electron microscopy (SEM). The effects of capsanthin extract and cap-DPGS-1000 micelles on a human triple-negative breast cancer cell line (MDA-MB-231) were tested to check the cell viability, proliferation and cytotoxicity of the micelles. The solubility of encapsulated cap-DPGS-1000 micelles in water is greatly enhanced and leads to an increased scope for localized drug delivery, a better delivery option for treating residual cancerous tumours. The encapsulated capsanthin showed a sustained release in simulated intestinal fluid (pH=6.8). Our research proposes a sustained drug delivery system that ensures effective and controlled release to the affected site. The characterization data revealed no change in the structure and functional groups in the encapsulated capsanthin. The IC50 value of the cap-DPGS-1000 micelles against MDA-MB-231 breast cancer cells was (3.10±1.09) μg/mL, which is much lower than of capsanthin extract ((81.1±1.5) μg/mL). Capsanthin extract and capsanthin-loaded micelles are promising drug candidates to induce apoptosis and increase reactive oxygen species (ROS) in cancer cells. The result shows the cytotoxic effect of capsanthin and capsanthin-loaded micelles on MDA-MB-231 cell line for the first time. Capsanthin from sweet red pepper (Capsicum annuum) showed remarkable cytotoxic effect on the triple-negative MDA-MB-231 cell line.

Development and evaluation of Panax notoginseng saponins contained in an in situ pH-triggered gelling system for sustained ocular posterior segment drug delivery

Abstract Objective: This study aimed to lay the foundation for the research on Panax notoginseng saponins (PNS) in pH-sensitive in situ gel and the development and improvement of related preparations. Methods: We used Carbopol®940, a commonly used pH-sensitive polymer, and the thickener hydroxypropyl methylcellulose (HPMC E4M) as an ophthalmic gel matrix to prepare an ophthalmic in situ gel of PNS. In addition, formula optimization was performed by assessing gelling capability with the results of in vitro release studies. In vitro (corneal permeation, rheological, and stability) and in vivo (ocular irritation and preliminary pharmacokinetics in the vitreous) studies were also performed. Results: The results demonstrated that the in situ gelling systems containing PNS showed a sustained release of the drug, making it an ideal ocular delivery system for improving posterior ocular bioavailability. Conclusions: This study lays the foundation for the research of PNS contained in an in situ pH-triggered gel as well as the development and improvement of related preparations. It concurrently traditional Chinese medicine with a contemporary in situ gelling approach to provide new directions for the treatment of posterior ocular diseases such as diabetic retinopathy.

Formulation development and in vitro Evaluation of sustained release matrix tablets of Cefpodoxime proxetil

The present focus is on the development of sustained release formulations due to its inherent boons. There are several advantages of sustained release drug delivery over conventional dosage forms like improved patient compliance, reduction in fluctuation and increased safety margin of potent drug. The present study was aimed to prepare a sustained drug delivery system to design a controlled release oral dosage form of Cefpodoxime proxetil. The sustained release matrix tablets of Cefpodoxime proxetil were prepared by wet granulation and evaluated for different parameters such as weight variation, drug content, thickness, hardness, friability and In vitro release studies. The in vitro dissolution study was carried out for 12 hours using USP (Type- II) paddle apparatus in hydrochloride (0.1N) as dissolution media for first 2 hours and phosphate buffer (pH 6.8) for next 10 hours. Based on the in vitro dissolution data, formulation F8 was selected as the best formulation from Cefpodoxime proxetil formulations (F1 – F9) as the drug release was retarded up to 12 hours with 96.29 % and followed zero order release kinetics & drug release mechanism was diffusion.

Floating Microsphere of Curcumin as Targeted Gastro-retentive Drug Delivery System

Microspheres carrier system made from natural or synthetic polymers used in sustained release drug delivery system. The present study involves formulation and evaluation of floating microspheres of Curcumin for improving the drug bioavailability by prolongation gastric residence time. Curcumin, natural hypoglycemic agent is a lipophilic drug, absorbed poorly from the stomach, quickly eliminated and having short half-life so suitable to formulate floating drug delivery system for sustained release. Floating microspheres of curcumin were formulated by solvent evaporation technique using ethanol and dichloromethane (1:1) as organic solvent and incorporating various synthetic polymers as coating polymer, sustain release polymers and floating agent. The final formulation were evaluated various parameters such as compatibility studies, micrometric properties, In-vitro drug release and % buoyancy. FTIR studies showed that there were no interaction between drug and excipients. The surface morphology studies by SEM confirmed their spherical and smooth surface. The mean particles size were found to be 416-618µm, practical yield of microspheres was in the range of 60.21±0.052% - 80.87±0.043%, drug entrapment efficiency 47.4±0.065% - 77.9±0.036% and % buoyancy 62,24±0.161% - 88.63±0.413%. Result show that entraptmency increased as polymer (Eudragit RS100) conc. Increased. The drug release after 12 hrs. was 72.13% - 87.13% and it decrease as a polymer (HPMC, EC) concentration was decrease.

Formulation and Characterization of Modified Release Microspheres of Lornoxicam Using Okra Gum as Natural Polymer and Ethyl Cellulose as Synthetic Polymer

Objective: The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. The arthritis, pain and inflammation are effectively treated with Lornoxicam, an effective NSAIDs. Because the drug is weakly acidic, it is absorbed easily in the GI tract, and has a short biological half-life of 3 to 5 hours. To meet the objectives of this investigation, we developed a modified release dosage form to provide the delivery of lornoxicam at sustained rate which was designed to prolong its efficacy, reduce dosage frequency, and enhance patient compliance. The present research work was focused on the development of lornoxicam microspheres using natural polymer like okra gum extracted from the pods of Abelmoschus esculentus Linn. and synthetic polymer like ethyl cellulose along with sodium alginate prepared by Ca2+ induced ionic-gelation cross-linking in a complete aqueous environment were successfully formulated.
 Materials and Method: The microspheres were prepared by using sodium alginate with natural polymer (okra gum) and synthetic polymer (ethyl cellulose) in different ratios by Ca2+ induced ionic-gelation cross-linking. The formulations were optimized on the basis of drug release up to 12 hrs. The physicochemical characteristics of Lornoxicam microspheres such as drug polymer interaction study by Fourier Transform Infrared (FTIR) and further confirmation by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The formulated microspheres were characterized for particle size, percentage drug entrapment efficiency, micromeritic properties, surface morphology, percentage swelling index, in-vitro drug release study and mechanism of drug release.
 Results and Discussion: The FTIR Spectra revealed that there was no interaction between polymer and Lornoxicam which was further confirmed by DSC and XRD. All the formulated Lornoxicam microspheres were spherical in shape confirmed by SEM. The microspheres exhibited good flow properties and also showed high percentage drug entrapment efficiency. All the batches have excellent flow properties with angle of repose in the range of 25.38° ± 0.04 to 30.41° ± 0.07, carr’s index and hausner’s ratios in the range of 10.40% ± 0.018 to 16.66% ± 0.012 and 1.128 ± 0.09 to 2.225 ± 0.01, respectively. The optical microscopic studies revealed that the mean particle size of all the formulations were found in the range of 819.46 ± 0.07 to 959.88 ± 0.02 μm and percentage of drug entrapment were found to be between 72.35 ± 0.02 to 90.00 ± 0.05. Swelling index of prepared microspheres revealed that with increasing the polymer ratios, there were increase in the swelling of prepared microspheres, showing in the range of 600.76 ± 0.42 to 690.11 ± 0.03% for okra gum microspheres at the end of 9 hr in comparison with ethyl cellulose microspheres which ranges between 179.71 ± 0.07 to 227.73 ± 0.05% at the end of 7 hr. In-vitro drug release of prepared microspheres formulation code LSO4 and LSE4 were found to be 88.654 ± 0.25% and 93.971 ± 0.20% respectively at the end of 12 hr. It was suggested that increase in polymer concentration, the drug release from the prepared microspheres got retarded producing sustained release of lornoxicam. In-vitro drug release data obtained were fitted to various release kinetic models to access the suitable mechanism of drug release. Drug release from lornoxicam-loaded alginate-okra gum microspheres followed a pattern that resembled sustained release (Korsemeyer-Peppas model) (R2 = 0.9925 to 0.9951), and n ≤ 1 indicated anomalous diffusion (non-Fickian), supercase-II transport mechanism LSO4 (n = 1.039) over a period of 12 hour underlying in-vitro drug release. Moreover, zero order model (R2 = 0.9720 to 0.9949) were found closer to the best-fit Korsemeyer - Peppas model.
 In addition, the drug release from lornoxicam-loaded alginate-ethyl cellulose microspheres also follow Korsemeyer-Peppas model (R2 = 0.9741 to 0.9973) with near to Hixson-Crowell model (R2 = 0.9953 to 0.9985) and n < 1 indicated non-Fickian diffusion or anomalous transport mechanism. Moreover, first order model with non-Fickian diffusion mechanism (R2 = 0.9788 to 0.9918) were found closer to the best-fit Korsemeyer-Peppas model/ Hixson-Crowell model.
 Conclusion: The present study conclusively demonstrates the feasibility of effectively encapsulating Lornoxicam into natural polymer (okra gum) and synthetic polymer (ethyl cellulose) to form potential sustained drug delivery system. In conclusion, drug release over a period of 12 hrs, could be achieved from these prepared microspheres. A pH-dependent swelling and degradation of the optimized microspheres were also observed, which indicates that these microspheres could potentially be used for intestinal drug delivery.

Formulation and Development Matrix Tablets Of Methimazole

Methimazole is active pharmaceutical ingredient effectively utilized in hyperthyroidism. Methimazole inhibits peroxidase as well as iodine interactions with thyroglobulin to produce triiodothyronine with thyroxine. Methimazole shows very low protein binding (1-10%) bounds to plasma proteins and easily metabolized by liver. In this investigation, efforts given to develop a sustained release matrix tablet of Methimazole. Sustained release drug delivery systems are for a maximum of 24 hours clinical effectiveness. Such systems are primarily for the drugs of short elimination half-life. However, drugs with long half-life also qualify if a reduction in steady state fluctuation is desired. Matrix tablets of methimazole were prepared by utilizing direct compression method. HPMC along with Sodium carboxy methyl cellulose used to retard drug release from the dosage form. Matrix tablets of methimazole were evaluated for different quality control test to improve quality of the product. In vitro release study of methimazole matrix tablets shows that polymer percentage used in the formula is enough to extend the release of the drug for at least 12 hr. In dissolution study of matrix of methimazole formulation F2 shows maximum drug release 97.93 % at the end of 6 hours while F1 shows least 83.64 %. Keywords: Matrix tablet, Methimazole, Sustained Release

Plants as pharmaceutical excipients in oral sustained drug delivery systems: A review

Plants and their derivatives have contributed immensely to drug development for their application as medicinal agents or as excipients in preparation of new drug delivery systems. Their use keeps increasing by the day. The rich, yet-to-be fully tapped vegetation available in the African sub-region puts it with great potential to be the next global destination as sources for pharmaceutical excipient. This work reviews published articles on plants and derivatives that have been employed so far in modifying drug delivery. Published articles from databases of PubMed, science direct and google scholar were sourced. Obtained manuscripts were screened for relevance to the topic and currency from reading through the abstract and scanning the body of the work. Gums and mucilages as plant derivatives in their natural form or as changed forms have been well investigated for use in controlled drug delivery. Some of these have been as functional in modifying drug release as many commercially employed excipients in drug delivery. Many plants and plant-derived polymers are generally regarded as safe, easily cultivated, show good functionality as drug additives and can be modified to improve on any less desirable property. Taking advantage of these positive factors will open doors for optimal use of these naturally endowed pharmaceutical excipients

Design and evaluation of chitosan-amino acid thermosensitive hydrogel.

Chitosan/glycerophosphate thermosensitive hydrogel crosslinked physically was a potential drug delivery carrier; however, long gelation time limits its application. Here, chitosan-amino acid (AA) thermosensitive hydrogels were prepared from chitosan (CS), αβ-glycerophosphate (GP), and l-lysine (Lys) or l-glutamic acid (Glu). The prepared CS-Lys/GP and CS-Glu/GP hydrogel showed good thermosensitivity and could form gels in a short time. The optimal parameters of CS-Lys/GP hydrogel were that the concentration of CS-Lys was 2.5%, the ratio of CS/Lys was 3.5/1.0, the ratio of CS-Lys/GP was 4.5/1.0. The optimal parameters of CS-Glu/GP hydrogel were that the concentration of CS-Glu was 3.0%, the ratio of CS/Glu was 2.0/1.0, and the ratio of CS-Glu/GP was 4.0/1.5. Chitosan-amino acid (CS-AA) thermosensitive hydrogel had a three-dimensional network structure. The addition of model drug tinidazole (TNZ) had no obvious effect on the structure of hydrogel. The results of infrared spectroscopy showed that there were hydrogen bonds between amino acids and chitosan. In vitro release results showed that CS-Lys/GP and CS-Glu/GP thermosensitive hydrogels had sustained release effects. Thus, the chitosan-amino acid thermosensitive hydrogels hold great potential as a sustained release drug delivery system.

Implementation of Quality by Design Principles for the Evolution of Optimized Sustained Release Drug Delivery System

Aim: The aim of the present work is the implementation of Quality by Design principles for the evolution of optimized sustained release drug delivery system. Background: Quality by Design (QbD) approach refers to an advance approach to develop an optimized dosage form. QbD has become a vital modern scientific approach to develop a quality dosage form. In the modern era of science, researchers can develop an optimized dosage form with least effort, money and manpower. Objectives: Objective of the research work was the successful development of optimized floating bioadhesive tablets of glipizide using floating-bioadhesive potential of cellulosic polymer and carbomersusing quality by design (QbD) approach. Methods: Quality Target Product Profile (QTPP) of drug delivery system was defined as well as critical quality attributes (CQAs) were identified. A face centered central composite design (CCD) was utilized in assessing the impact of the individual critical material attribute (CMA) like Hydro Propyl Methyl Cellulose K4M(HPMC K4M)and Carbopol 934P (CP 934P) and their interactions, using least experimentation. Formulations were developed and quantitative impact on CQAs was determined using mathematical model. The optimized formulation was obtained and characterized for in-vitro as well as in-vivo parameters. Results: A Fishikawa diagram and Failure Mode and Effect Analysis (FMEA) was performed to identify potential failure modes associated with the dosage form. The optimum formulation was embarked upon using mathematical model developed yielding desired CQAs followed for confirmation of data. Sustained release drug delivery system was successfully developed by using QbD approach. In-vivo X-ray imaging in rabbit and γ-scintigraphic study in manconfirmed the buoyant nature of the mucoadhesive floating tablet for 8 h in the upper gastrointestinal tract. Conclusion: Optimized formulation shows phenomenal floating, bioadhesive properties and drug release retardation characteristics, utilizing a mixture of cost-effective polymers Hence, QbD approach may be regarded as an important tool in development of floating bioadhesive CR dosage forms.

PH-responsive and sustained release drug delivery system of BSA coated CDs-DOX

BackgroundThe drugs are easily cleared and lack of targeting in chemotherapy, thus reducing its efficacy. A novel pH- responsive drug delivery system based on carbon quantum dots (CDs) was proposed. CDs have low toxicity and good biocompatibility and can be electrically combined with doxorubicin (DOX). The bovine serum albumin (BSA), an endogenousx substance, could be used as a protein model for constructing a novel lipoprotein-like nanocarrier. In this study, we introduced BSA into the drug delivery system and prepared a stable drug delivery system BSA@CDs-DOX. The system was characterized by UV-Vis, fourier infrared spectroscopy, transmission electron microscopy and fluorescence spectroscopy, and its stability, drug loading efficiency, coating efficiency and drug release in vitro were investigated. The release of drug from the system was tracked by the fluorescence properties of CDs. ResultsThe stability of the BSA@CDs-DOX system was obviously enhanced in various environments. The in vitro release profile was prolonged, and the cumulative release ratio at pH = 5.0 was 7.5 times higher than that at pH = 7.4. The drug side effects on the normal cells were significantly reduced and the killing effect on cancerous cells was improved in longer time. Excellent and sustained migration resistance was observed in 72 h. The drug uptake process and cellular state were evaluated visually in real time until 72 h. ConclusionThe stable and sustained release BSA@CDs-DOX system showed good application prospect in chemotherapy of tumors.

Technologies in Bilayer Tablet Manufacturing: A Review

Bilayer tablet is a recent time for the successful development of controlled release formulation along with various quality to provide a way of the successful drug delivery system. Over the past 30 years stated that the cost and complications involved in marketing new drug entities have increased, with consequent recognition of therapeutic advantages of controlled drug delivery, greater attention has been concentration on development of sustained or controlled release drug delivery systems. Bilayer tablet it is used in the different aspect for anti-inflammatory and analgesic. Bilayer tablet incidental release of two drugs in combination, separate two incompatible substance and also for sustained release tablet in which one layer is immediate release as initial dose and second layer is maintenance dose. Bilayer tablet is enhancing beneficial technology to control the shortcoming of the single layered tablet. There is various application used in the bilayer tablets.

DESIGN AND EVALUATION OF HERBAL HEPATOPROTECTIVE MATRIX TABLET CONTAINING METHANOLIC EXTRACT OF CORDIA DICHOTOMA LEAVES

Cordia dichotoma, belonging to the family Boraginaceae, is a medium sized tree with a short, usually crooked trunk, which is found throughout India. C. dichotoma is beneficial in conditions of liver disease and inflammation. The present investigation was designed to develop a sustained release herbal matrix tablet containing C. dichotoma leaves extract for the treatment of liver disorders by exploiting the knowledge of the traditional system of medicine. Three herbal tablet formulations of methanolic extract of C. dichotoma were developed by the wet granulation method using the blend of hydrophilic and hydrophobic polymers like HPMC E-5, sodium carboxymethyl cellulose, Poloxamer 188, and ethyl cellulose. The tablets were evaluated for physicochemical properties and in vitro release study followed by stability testing to assess its shelf life. In vitro hepatoprotective effect was also studied, which is based on protection of human liver-derived HepG2 cells against CCl4 exposed toxicity. Physicochemical properties were found to be within limits. The percentage of drug release after 12 h was found to be 75.65, 79.75, and 82.49 for formulation F-1, F-2 and F-3, respectively. The proposed study demonstrates that developed herbal matrix tablet can serve as a successful sustained drug delivery system with the added benefit of no side effects for control and cure of chronic conditions of the liver.

Honokiol-Loaded Methoxy Poly (Ethylene Glycol) Polycaprolactone Micelles for the Treatment of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD), a multifactorial age-related retinal hypoxic disorder resulting in irreversible loss of vision, is the foremost cause of blindness in the United States. Current treatment strategies involve multiple intraocular injections of antivascular endothelial growth factor (VEGF) agents into the vitreous of eye. In addition to the challenges of drug localization and targeted delivery, the need of frequent injections into the eye raises patient compliance issues, and thus call for development of sustained drug delivery systems. In this study, a sustained drug delivery system was prepared by loading an antihypoxia-induced factor (HIF) agent, honokiol (HON), into methoxy poly (ethylene glycol) polycaprolactone (MPEG-PCL) polymer. These HON-MPEG-PCL micelles were characterized by evaluating size, ζ potential, in vitro drug release profile, and morphology by transmission electron microscopy. The cytotoxic nature of developed micelles was assessed on human retinal pigment epithelial cell line (ARPE-19) cells by cytotoxicity assay. The cellular uptake and HIF and VEGF expression levels were determined in in vitro settings. Micelles formed had a particle size of 30.8 ± 0.8 nm with the poly dispersity index of 0.19 ± 0.0004 and ζ potential was found to be -5.46 ± 0.49 mv. Entrapment efficiency was calculated to be 64 ± 0.135%. In vitro drug release showed sustained release of drug from the formulation. Result from in vitro cytotoxicity study confirmed noncytotoxic nature of HON-MPEG-PCL micelles compared to HON drug solution. Furthermore, enzyme-linked immunosorbent assay studies performed showed the periodic downregulation of HIF and VEGF, which are major growth factors involved in underlying mechanism of AMD. The results showed successful development of HON-MPEG-PCL micelles, which may be useful for the effective treatment of AMD.

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief.

BackgroundWe utilized the destabilization of medial meniscus (DMM)-induced mice to illustrate the osteoarthritis (OA) suppressing and pain-relieving effects of a novel prolonged-release intra-articular (IA)-dexamethasone-loaded thermo-sensitive hydrogel (DLTH).MethodsThe effects of temperature and pH on DLTH formation and in vitro DLTH release profile were assessed. C57BL/6J mice were randomly divided into three groups: Ctrl group, Model group and DLTH group. The DLTH group received joint injections of 10 µL DLTH (1 mg/kg) into the right knee once a week from week 2 to week 11. We performed micro-computed tomography (Micro-CT) and histological analyses of safranin O-fast green, hematoxylin and eosin, and tartrate-resistant acid phosphatase in knee joints. We also carried out immunohistochemical (IHC) staining for matrix metalloproteinase-9 (MMP-9), MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) in cartilage and Ki-67 in synovia. Pain behavioral testing was carried out in all mice. The serum content of prostaglandin E2 (PGE2) and real-time polymerase chain reaction (PCR) of inflammatory cytokines and pain-related factors in dorsal root ganglia (DRGs) were evaluated.ResultsIt took 20 minutes to form DLTH at pH 7.0 and 37 °C. The cumulative release profiles of dexamethasone (Dex) from DLTH at 37 °C revealed a rapid release in the first 24 h and a sustained slow release for 7 days. In vivo study illustrated that DLTH attenuated OA bone destruction and ameliorated synovitis and progression of OA in DMM-induced mice. The chondroprotective effects of DLTH were mediated by decreased expressions of MMP-9, MMP-13, and ADAMTS-5. The results showed that IA-DLTH exerted pain-relieving effects in OA mice. Upregulation of nociceptive response time (NRT) and downregulations of serum PGE2, inflammatory factors, and pain-related mediators in DRGs of mice in the DLTH group were recorded.ConclusionsData presented in this study elucidated that DLTH exhibited a long and lasting Dex release and it is a potential sustainable drug delivery system (DDS) to treat OA locally. IA-DLTH injection exerted chondroprotective and pain-relieving effects in DMM-induced arthritis. The involvement of MMP-9, MMP-13, ADAMTS-5, and inflammatory and pain-related factors, may account for the suppression of OA progression and pain.

Green Synthesis of Thermo-Responsive Hydrogel from Oil Palm Empty Fruit Bunches Cellulose for Sustained Drug Delivery.

Drug delivery is a difficult task in the field of dermal therapeutics, particularly in the treatment of burns, wounds, and skin diseases. Conventional drug delivery mediums have some limitations, including poor retention on skin/wound, inconvenience in administration, and uncontrolled drug release profile. Hydrogels able to absorb large amount of water and give a spontaneous response to stimuli imposed on them are an attractive solution to overcome the limitations of conventional drug delivery media. The objective of this study is to explore a green synthesis method for the development of thermo-responsive cellulose hydrogel using cellulose extracted from oil palm empty fruit bunches (OPEFB). A cold method was employed to prepare thermo-responsive cellulose hydrogels by incorporating OPEFB-extracted cellulose and Pluronic F127 (PF127) polymer. The performance of the synthesized thermo-responsive cellulose hydrogels were evaluated in terms of their swelling ratio, percentage of degradation, and in-vitro silver sulfadiazine (SSD) drug release. H8 thermo-responsive cellulose hydrogel with 20 w/v% PF127 and 3 w/v% OPEFB extracted cellulose content was the best formulation, given its high storage modulus and complex viscosity (81 kPa and 9.6 kPa.s, respectively), high swelling ratio (4.22 ± 0.70), and low degradation rate (31.3 ± 5.9%), in addition to high t50% value of 24 h in SSD in-vitro drug release to accomplish sustained drug release. The exploration of thermo-responsive cellulose hydrogel from OPEFB would promote cost-effective and sustainable drug delivery system with using abundantly available agricultural biomass.

Ultrasound Triggered Drug Release from Affinity-Based β-Cyclodextrin Polymers for Infection Control.

This work demonstrates a slow, sustained drug delivery system that provides on-demand delivery bursts through the application of pulsed therapeutic ultrasound (TUS). Insoluble β-cyclodextrin-polymer (pCD) disks were loaded with a saturated antibiotic solution of rifampicin (RIF) and used for drug delivery studies. To obtain on-demand release from the implants, TUS was applied at an intensity of 1.8 W/cm2. The therapeutic efficacy of the combination treatment was assessed in bacterial culture via an in vitro Staphylococcus aureus bioluminescence assay. The results demonstrated that the application of pulsed TUS at 3 MHz and 1.8 W/cm2 to pCD implants leads to a significantly higher short-term burst in the drug release rate compared to samples not treated with TUS. The addition of TUS increased the drug release by 100% within 4 days. The pCD disk + RIF stimulated with TUS showed a comparatively higher bacterial eradication with CFU/mL of 4.277E+09, and 8.00E+08 at 1 and 24 h compared with control treated bacteria at 1.48E+10. Overall, these results suggest that the addition of pulsed TUS could be an effective technology to noninvasively expedite antibiotic release on demand at desired intervals.

Sustained Release Matrix Tablet: An Overview

Sustained Release is also a promising method for reducing medication side effects by preventing the therapeutic concentration of the drug from fluctuating in the body.The basic rationale of a sustained drug delivery system is to optimise a drug's biopharmaceutical, pharmacokinetic, and pharmacodynamic properties in order to maximise utility, minimise side effects, and cure the disease. The drug release rate is regulated by the matrix. HPMC and other release retardants can help with sustained release, so they are used as a key excipient in the formulation.The method entails compressing a mixture of medication, retardant material, and additives directly to shape a tablet with the drug embedded in a retardant matrix core; instead, granulation may be done prior to compression. Hydrophilic, hydrophobic, mineral, and biodegradable matrices may be used.To assess the drug release rate, in-vitro dissolution tests may be used. The primary goal of continuous release types is to improve drug therapy, which is determined by the relationship between the advantages and disadvantages of using one.