Drug Delivery Systems Research Articles

Dextran-based Drug Delivery Approaches for Lung Diseases: A Review.

Respiratory disorders, such as tuberculosis, cystic fibrosis, chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary inflammation, are among the most prevalent ailments in today's world. Dextran, an exopolysaccharide formed by Leuconostoc mesenteroides (slimeproducing bacteria), and its derivatives are investigated for several therapeutic utilities. Dextranbased drug delivery system can become an innovative strategy in the treatment of several respiratory ailments as it offers numerous advantages, such as mucolytic action, airway hydration, antiinflammatory properties, and radioprotective effect as compared to other polysaccharides. Being biocompatible, flexible hydrophilic nature, biodegradable, tasteless, odourless, non-mutagenic, watersoluble and non-toxic edible polymer, dextran-based drug delivery systems have been explored for a wide range of therapeutic applications, especially in lungs and respiratory diseases. The present article comprehensively discusses various derivatives of dextran with their attributes to be considered for drug delivery and extensive therapeutic benefits, with a special emphasis on the armamentarium of dextran-based formulations for the treatment of respiratory disorders and associated pathological conditions. The information provided will act as a platform for formulation scientists as important considerations in designing therapeutic approaches for lung and respiratory diseases. With an emphasis on lung illnesses, this article will offer an in-depth understanding of dextran-based delivery systems in respiratory illnesses.

Necroptosis and autophagy in cisplatinum-triggered nephrotoxicity: Novel insights regarding their prognostic and diagnostic potential

Necroptosis is an innovative class of programmed autophagy (Atg) and necrosis; considered as a type of homeostatic housekeeping machinery that have observed an escalating concern due to its power in alleviating Cisplatinum-induced nephrotoxicity. This article elucidated in details the prospective role of both autophagy and necroptosis on Cisplatinum-triggered nephrotoxicity and investigating more potent therapy via lactoferrin and Ti-NPS conjugation. Cisplatinum is a commonly used chemotherapeutic drug; one of the limiting adverse actions of cisplatinum is renal toxicity. Upon cisplatinum administration, autophagy is highly stimulated in the kidney to shield against nephrotoxicity. Atg is a lysosomal degradation process which discards detorirated proteins to retain cell homeostasis. This article summarizes necroptosis progress in reconizing cisplatinum nephrotoxicity and debates how this progress can help in discovering more potent therapy via lactoferrin and Ti-NPS conjugation via monitoring autophagy and apoptotic biomarkers X-box-binding protein 1 (XBP), C/EBP homologous protein (CHOP), hypoxanthine phosphoribosyltransferase-1 (HPRT), FKBP prolyl isomerase 1B (FKBP), Cellular myelocytomatosis oncogene (C-myc), tumor suppressor gene (P53) and tumor necrosis factor (TNF-α). Cisplatinum nephrotoxicity was conducted in rat model via an oral dose of (2mg/kg BW) for one month furthermore a comparative study was conducted among TiNPs-loaded Cisplatinum and Lactoferrin loaded Cisplatinum. Loaded drug delivery system counteracted Cisplatinum triggered nephrotoxicity via controlling autophagy and apoptotic XBP, CHOP, HPRT, FKBP, C-myc, P53 and TNF-α signaling pathway.

In Situ Photo Responsive Biodegradable Nanoparticle Forming Intrauterine Implant for Drug Delivery to Treat Ovarian Diseases: A Rationale-based Review.

Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases.

Synthesis and Biological Evaluation of Gold Nanoparticles Drug Delivery System as Anti-Rheumatoid Arthritis Agents

Synthesis and Biological Evaluation of Gold Nanoparticles Drug Delivery System as Anti-Rheumatoid Arthritis Agents

ROS responsive nanozyme loaded with STING silencing for the treatment of sepsis-induced acute lung injury

Acute lung injury (ALI) is a common complication of sepsis and a leading cause of mortality in septic patients. Studies indicate that STING may play a crucial role in the pathogenesis of sepsis-induced ALI by interacting with the PARP-1/NLRP3 pathway. Therefore, targeting STING inhibition has potential as a novel therapeutic strategy for ALI. However, effective inhibition remains challenging due to the widespread expression of STING across various tissues. In this study, we developed a nanozyme-based drug delivery system, DSPE-TK-mPEG-MnO2@siSTING (abbreviated as DTmM@siSTING), using DSPE-TK-mPEG-MnO2 as the carrier, and characterized it via scanning electron microscopy, dynamic light scattering, nanoparticle size analysis, and gel electrophoresis. To evaluate the therapeutic effects of DTmM@siSTING, an in vitro ALI cell model and an in vivo ALI mouse model were established, assessing the nanozyme's impact on ROS levels, inflammatory responses, and the PARP-1/NLRP3 pathway in sepsis-induced ALI. Results demonstrated that DTmM@siSTING exhibited good physiological stability. In vitro, DTmM@siSTING significantly reduced ROS levels, myeloperoxidase activity, and expression of inflammatory cytokines, while also inhibiting PARP-1/NLRP3 pathway activation. In vivo experiments further revealed that DTmM@siSTING effectively delivered siSTING to the lungs, mitigating sepsis-induced ALI and associated inflammatory responses. Additionally, DTmM@siSTING displayed excellent biocompatibility. In summary, our findings suggest that DTmM@siSTING significantly enhances the therapeutic efficacy of siSTING, alleviating ALI by inhibiting ROS production, inflammatory responses, and activation of the PARP-1/NLRP3 pathway. This novel approach presents a promising therapeutic avenue for sepsis-induced ALI.

Review on Oral Osmotic Tablet

Traditional oral medication delivery methods provide the drug with an immediate release and an efficient concentration at the intended location. Such a dosage regimen could lead to unexpected, ever-changing plasma concentrations. As a result, numerous regulated medication delivery systems are created. Among these, osmotic drug delivery systems (ODDS) and pulsatile drug delivery systems (PDDS) are becoming more and more significant because they improve patient treatment efficacy and compliance by delivering the medicine at precise times based on the course and physiological requirements of the disease. They regulate the drug’s delivery by using the osmotic pressure theory.To a significant extent, the drug’s release is unaffected by GIT physiological variables. Both targeted and systemic medication delivery are possible with these methods. The theoretical idea of drug delivery, various oral osmotic drug delivery system types, factors influencing the drug delivery system, benefits and drawbacks of these delivery systems, fundamental osmotic system components, evaluation parameters, difficulties, and emerging technologies in oral controlled drug delivery are all “highlighted” in this review.

Medicated herbal chewing Gum to treat ulcers in mouth using Licorice and Capsicum annuum

This study explores the formulation and evaluation of herbal chewing gum containing extracts from Licorice (Glycyrrhiza glabra) and Capsicum Annuum, aimed at treating mouth ulcers. Licorice derived from roots. are known for their medicinal properties, it contains glycyrrhizin which is responsible for its sweet taste, including effects on sore throats, reduce inflammation and aid digestion. They contain various chemical compounds flavonoids such as such as liquirtin, rhamnoliquirilin, liquiritigenin, prenyllicoflavone A, glucoliquiritin apioside, metho-xyphaseolin, shinpterocarpin, shinflavanone, licopyranocoumarin, glisoflavone, licoarylcoumarin, coumarin-GU-12 and saponins namely glycyrrhizin flavonoids. While Capscicum annuum is recognized for its anti-oxidant, analgesic, insecticidal and anti ulcer properties, containing phytochemicals like carotenoids, flavonoids, capsaicinoids, phenolic compounds, vitamins and minerals. The preparation of the herbal chewing gum involved incorporating these extracts along with other necessary ingredients. Triethanolamine was added to adjust the pH to a suitable range (6.7-7.2) for oral mucosa compatibility. The study emphasizes that chewing gums serve as mobile drug delivery systems, allowing for the incorporation of herbal medicines for treating mouth ulcers. The convenience of chewing gum enables self-medication without the need for water, with active substances being released during chewing. This method facilitates local treatment of mouth diseases and systemic delivery through absorption via the buccal mucosa the herbal chewing gum represents an effective drug delivery system.

Nanoparticle-enhanced near-infrared fluorescence probes as a new frontier in cancer imaging

Recent advancements in nanotechnology have significantly enhanced the development of near-infrared fluorescence (NIRF) probes, positioning them as powerful tools in cancer imaging. This paper explores the unique advantages of nanoparticles incorporating NIR dyes, such as indocyanine green (ICG) and DiR, which exhibit deep tissue penetration and minimal background autofluorescence. The enhanced permeability and retention (EPR) effect facilitates selective accumulation in tumor tissues, enabling sophisticated imaging and precision-targeted drug delivery systems. This review highlights the remarkable potential of NIRF imaging techniques in molecular diagnostics, emphasizing their ability to differentiate malignant tissues at a molecular level. Additionally, we discuss various NIRF dye classifications, including cyanine and BODIPY-based probes, along with the development of multifunctional agents that enhance imaging specificity and therapeutic effectiveness. The integration of advanced targeting capabilities, including the use of antibodies and small molecules, further improves the precision of these imaging agents. While challenges remain regarding the pharmacokinetics and potential toxicity of nanoparticle-based probes, their capacity for real-time tumor tracking and the promise of multimodal imaging approaches underscore their transformative role in cancer diagnostics and treatment. By advancing the field of theranostics, nanoparticle-enhanced NIRF probes pave the way for personalized medicine and improved patient outcomes in oncology.

Design and development of minoxidil-loaded nano carrier-based transdermal gel of trans-ethosomes for transdermal delivery system: Invitro evaluation studies

The present aim of the study was to develop a transdermal drug delivery system of the Nano-carrier-based Minoxidil-loaded transethosomal gel. In this study, we used Soyaphopshotidylcholine as a vesicle-forming agent and Sodium deoxycholate as a surfactant, and vesicle stabilizer as excipients. The Minoxidil transethosomes were prepared by thin film hydration technique. The prepared Minoxidil-loaded transethosomes (MTE) were evaluated and the particle size (189.83nm and 206.18nm), PDI(0.292 and 0.263), Zeta potential(-29.1mv and-28.2mv) and the entrapment efficiency (89.16±3.16 and 81.65±2.74) of MTE5 and MTE6. The MTE dispersion was further used to prepare gel, the gel base was prepared by using Carbopol, Xanthan gum, and HPMC K15. The optimized MTE-gel formulation was further evaluated, and the cumulative percentage of drug release was 98%, the 3 months stability studies show satisfactory results indicating good gel stability.

Development, characterization, and assessment of PLAROsomal vesicular system of curcumin for enhanced stability and therapeutic efficacy

Abstract Background Curcumin (CUR) is a natural polyphenol and one of the key phytoconstituents found in the rhizomes of Curcuma Longa. It exhibits various pharmacological properties, encompassing antioxidant, anticancer effects, antiseptic, and anti-inflammatory, among several others. A significant drawback of using CUR is its limited bioavailability, which primarily depends on gut microorganisms responsible for converting it into its bioavailable form. Therefore, the contemporary study intended to formulate a novel PLAROsomal vesicular delivery of CUR, i.e., CUR-PLAROsomes employing a design of experiments approach to examine the influence of various process parameters, such as particle size and drug percentage release. Result The prepared CUR-PLAROsomes were characterized for their physicochemical properties using various hyphenated tools. The CUR-PLAROsomes exhibited sizes ranging from 40 to 300 nm, and the optimized batch demonstrated a drug entrapment of 86.38 ± 0.22%. In-vitro anticancer studies were conducted using human colorectal adenocarcinoma cells (COLO320DM) and human breast adenocarcinoma (MCF-7). CUR-PLAROsomes exhibited significant in-vivo anti-inflammatory potential against carrageenan-induced paw edema. CUR-PLAROsomes were more potent against COLO320DM and MCF-7 cell lines, even at lower concentrations, than pure CUR. Conclusion Furthermore, based on the observations, it exhibits potential as an anti-inflammatory agent, suggesting that PLAROsomes are an effective vesicular drug delivery system. Highlights Newly introduced PLARosome is a next generation of Liposomes which have gain popularity owing to its better adaptability to overcome leakage problem of vesicular drug delivery system. This is the pioneer attempt to prepare Curcumin-loaded PLARosome as an anti-cancer and anti-inflammatory activity. Nano size of the PLAROsomes may contribute to enhance the efficacy of Curcumin as a target specific drug delivery system. Site specific delivery of phytoconstituents is possible by use of PLAROsomes as a novel drug delivery system. Graphical abstract

Physical, biochemical, and biological characterization of olive-derived lipid nanovesicles for drug delivery applications

AbstractExtracellular vesicles (EVs) have shown great promise as drug delivery system (DDS). However, their complex and costly production limit their development for clinical use. Interestingly, the plant kingdom can also produce EV-like nanovesicles that can easily be isolated and purified from a large quantity of raw material at a high yield. In this study, olive-derived nanovesicles (ODNVs) were isolated from raw fruits using serial centrifugations and their physical and biological features characterized to demonstrate their promising potential to be used as a DDS. Nanotracking particle analysis indicated an average size of 109.5 ± 3.0 nm and yield of 1012 ODNVs/mL for the purest fraction. Microscopy imaging, membrane fluidity assay and lipidomics analysis showed the presence of a rich lipid bilayer that significantly varied between different sources of ODNVs but showed a distinct signature compared to human EVs. Moreover, ODNVs were enriched in PEN1 and TET8 compared to raw fruits, suggesting an extracellular origin. Interestingly, ODNVs size and yield stayed unchanged after exposure to high temperature (70 °C for 1 h), wide pH range (5–10), and 50–100 nm extrusion, demonstrating high resistance to physical and chemical stresses. This high resistance allowed ODNVs to stay stable in water at 4 °C for a month, or with the addition of 25 mM trehalose for long-term freezing storage. Finally, ODNVs were internalized by both 2D and 3D cell culture without triggering significant cytotoxicity and immunogenicity. Importantly, the anticancer drug doxorubicin (dox) could be loaded by passive incubation within ODNVs and dox-loaded ODNVs decreased cell viability by 90% compared to only 70% for free dox at the same concentration, indicating a higher efficiency of drug delivery by ODNVs. In addition, this high cytotoxicity effect of dox-loaded ODNVs was shown to be stable after a 2-week storage at 4 °C. Together, these findings suggested that ODNVs represent a promising candidate as drug nanocarrier for various DDS clinical applications, as demonstrated by their biocompatibility, high resistance to stress, good stability in harsh environment, and improvement of anticancer drug efficacy.

Correction: Jin et al. A pH-Responsive DNA Tetrahedron/Methotrexate Drug Delivery System Used for Rheumatoid Arthritis Treatment. J. Funct. Biomater. 2023, 14, 541

In the original publication [...]

Tripolar Bolalipids as Key Components of Sustained-Release Drug Delivery Systems

Tripolar Bolalipids as Key Components of Sustained-Release Drug Delivery Systems

Formulation development, characterization, and mechanistic PBPK modeling of metoclopramide loaded halloysite nanotube (HNT) based drug-in-adhesive type transdermal drug delivery system

Formulation development, characterization, and mechanistic PBPK modeling of metoclopramide loaded halloysite nanotube (HNT) based drug-in-adhesive type transdermal drug delivery system

Production of Polylactide Nanoparticles Loaded With Isoniazid and Vitamin C: A Promising Candidate for the Treatment of Resistant Forms of Tuberculosis

ABSTRACTNowadays, the method of directed transport of drugs is becoming increasingly important in medicine and pharmacology. It allows for increasing the concentration of delivered substances in a certain place and blocking or severely limiting their accumulation in healthy organs and tissues. One of the promising drug carriers used in the development of controlled drug delivery systems is polylactic acid (PLA). We were interested in using biodegradable polymeric nanoparticles (NPs) loaded with isoniazid (INH) and vitamin C (VC) which have sustained action, targeted delivery, high efficacy, and low toxicity. It will help to expand the use of these simple drugs for the rapid treatment of multidrug‐resistant forms of tuberculosis. Thus, in this work, PLA‐INH‐VC NPs were prepared by double emulsion method where several factors affecting particle size were investigated. TGA/DSC and IR spectroscopy studies identified the presence of molecularly dispersed drugs (INH and VC) in polylactide nanoparticles. VC was found to reduce the degradation of the polymer and thus prolonged the release of the drug from the polymer matrix. PLA‐INH‐VC nanoparticles were analyzed for mycobacterial activity and the nanoparticles were found to inhibit the growth of INH‐resistant mycobacteria.

FeS2@COF based nanocarrier for photothermal-enhanced chemodynamic/thermodynamic tumor therapy and immunotherapy via reprograming tumor-associated macrophages.

Developing high-performance nanomedicines to enhance antitumor efficacy remains a hot point in the field of biomedicine. In this study, we designed a versatile nanocomposite (FeS₂@COF-HA/AIPH) integrating covalent organic frameworks (COF) functionalized with pyrite (FeS₂) for synergistic photothermal (PTT), chemodynamic (CDT), thermodynamic (TDT) therapies, and immunotherapy. The superior photothermal effects and catalytic capabilities of FeS₂@COF enabled a minimally invasive PTT/CDT combination. The nanoplatform, with its mesoporous structure, also served as a drug delivery system, encapsulating the thermos-decomposable initiator AIPH. The hyaluronic acid (HA) coating not only improved tumor-targeting efficiency but also prevented nonspecific AIPH release. Under near-infrared (NIR) irradiation, the localized hyperthermia triggered AIPH decomposition, generating toxic alkyl radicals (•R) for TDT, further enhancing CDT efficiency. The combination of PTT, CDT, TDT, and immunotherapy led to potent antitumor effects with minimal systemic toxicity, both in vitro and in vivo. Notably, the nanoplatform effectively reprogrammed tumor-associated macrophages (TAMs) from an M2 to M1 phenotype, boosting antitumor immunity. This multifunctional platform thus offers a promising strategy for integrated PTT, CDT, TDT, and immune activation in tumor therapy.

Rg3-lipo biomimetic delivery of paclitaxel enhances targeting of tumors and myeloid-derived suppressor cells.

Liposomal drug delivery systems have revolutionized traditional cytotoxic drugs. However, the relative instability and toxicity of the existing liposomal drug delivery systems compromised their efficacy. Herein, we present Rg3-lipo, an innovative drug delivery system using a glycosyl moiety-enriched ginsenoside (Rg3). This system is distinguished by its glycosyl moieties exposed on the liposomal surface. These moieties imitate human cell membranes to stabilize and evade phagocytic clearance. The Rg3-lipo system loaded with paclitaxel (PTX-Rg3-lipo) demonstrated favorable bioavailability and safety in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys. With its glycosyl moieties recognizing tumor cells via the glucose transporter Glut1, PTX-Rg3-lipo inhibited gastric, breast, and esophageal cancers in human cancer cell lines, tumor-bearing mice, and patient-derived xenograft models. These glycosyl moieties selectively targeted myeloid-derived suppressor cells (MDSCs) through the glucose transporter Glut3 to attenuate their immunosuppressive effect. The mechanism study revealed that Rg3-lipo suppressed glycolysis and downregulated the transcription factors c-Maf and Mafb overcoming the MDSC-mediated immunosuppressive microenvironment and enhancing PTX-Rg3-lipo's antitumor effect. Taken together, we supply substantial evidence for its advantageous bioavailability and safety in multiple animal models, including nonhuman primates, and Rg3-lipo's dual targeting of cancer cells and MDSCs. Further investigation regarding Rg3-lipo's druggability will be conducted in clinical trials.

Double-crosslinked hydrogels and hydrogel beads formed by garlic protein hydrolysates for bioactive encapsulation and gastrointestinal delivery.

Garlic protein is one of the main components of garlic. It has several beneficial characteristics. This study aimed to characterize a double crosslinked hydrogel formed with alginate, calcium ions (Ca2+), and garlic protein hydrolysates (GPH), and to develop hydrogel beads for targeted delivery of bioactive constituents to the gastrointestinal tract. The results indicated that the degree of GPH hydrolysis was approximately 3% following trypsin treatment. The inner structure of the double crosslinked hydrogel showed a honeycomb pattern, with solid-like gel rheology and improved texture properties at a 4% (w/v) GPH concentration. The GPH-based hydrogel beads demonstrated pH sensitivity, swelling in near-neutral and alkaline environments, and the encapsulated paclitaxel (PTX) exhibited an amorphous phase with preferential release in intestinal conditions. The GPH group also achieved greater drug encapsulation efficiency than a soy protein hydrolysate (SPH) group, and proteomic analysis suggested that lower molecular weight and peptide charge favored the formation of peptide-integrated double crosslinking hydrogels. This work indicated that GPH was helpful and could inspire the development of drug delivery systems involving GPH with the required mechanical strength and target-release properties. © 2024 Society of Chemical Industry.

Formulation, Development and Evaluation of Pulsatile Tablets of Etoricoxib

Aim: This research aimed to develop a pulsatile drug delivery system (PDDS) for etoricoxib, selective COX-2 inhibitor analgesic, to address the limitations of conventional formulations by releasing the drug at specific intervals aligned with the circadian rhythm of pain. Method: Core tablets containing Etoricoxib were prepared by direct compression with varied concentrations of croscarmellose sodium as a superdisintegrant. The optimized core tablets were coated using hydrophilic (HPMC K4M) and hydrophobic (ethyl cellulose) polymers in different ratios to create press-coated pulsatile tablets with varying lag times. Physical properties hardness, thickness, friability, and disintegration, drug content uniformity, and in vitro release were evaluated. Results: The core tablets exhibited rapid drug release, with batch C3 showing 98.61% release within 60 minutes. Press-coated formulations with different polymer ratios exhibited varying lag times, with batch F3 achieving the optimal balance—providing a 4-hour lag time and 96.6% drug release over 8 hours. Stability studies confirmed the physical and chemical stability of the optimized formulation (F3) over 6 months under accelerated conditions. Conclusion: The developed press-coated pulsatile tablets of etoricoxib successfully achieved a controlled lag time and sustained drug release profile, making them suitable for chronopharmacological management of pain. Keywords: Etoricoxib, Pulsatile Drug Delivery System, Chronopharmacology, Press-Coated Tablets. etc

Timolol Maleate Microspheres: An Ingenious Carrier for Sustained Release Antihypertensive Formulation

Background: Timolol maleate is classified as a BCS Class I drug and functions as a non-selective β-adrenergic receptor blocker. Its ability to lower heart rate and cardiac output has led to its widespread use in the treatment of hypertension. Objective: Timolol maleate has a short half-life and is rapidly cleared from the body, which limits its therapeutic effectiveness, requiring frequent dosing and potentially affecting patient adherence. To overcome these challenges, sustained-release microspheres of Timolol maleate were developed using the ion gelation method. Method: The ion gelation technique was employed to create the microspheres due to its various advantages, including ease of use, scalability and gentle processing conditions. Results: All batches exhibited a comparatively lower swelling index in 0.1M HCl (pH 1.2) than in SIF (pH 6.8). It was observed that increasing the concentration of sodium alginate resulted in higher drug content. The microspheres were sized between 400 and 900 μm and demonstrated excellent flow characteristics. An optimized batch achieved an entrapment efficiency of 88.83% and released 92.15% of the drug over 7 hrs. Furthermore, stability studies conducted according to ICH Q1A(R2) for 3 months at 5±3°C and 25±2°C/60±5% RH indicated no significant changes in evaluation parameters. Conclusion: The optimized Timolol maleate-loaded microspheres effectively provided sustained drug release through the membrane over 7 hrs. This study contributes to the development of improved drug delivery systems for better hypertension management, addressing the unmet needs in patient compliance. Keywords: Timolol Maleate, Microspheres, Ion gelation method, Sodium alginate, Calcium chloride, Sustained release, Hypertension