Sustained Drug Delivery System Research Articles

Chlorogenic acid sustained-release gel for treatment of glioma and hepatocellular carcinoma

Chlorogenic acid (CGA) may provide an effective and safe option for tumor treatment. However, its application is limited because of short residence time in vivo and repeated administration required. A phospholipid-based in situ gel containing chlorogenic acid (CGA PG) was prepared via a simple way. The CGA PG exhibited good fluidity, easy injectability, high-drug-loading capacity, and suitable sustained-release behavior whether in vitro or in vivo. Furthermore, CGA PG could suppress tumor growth with no significant side effects. Overall, CGA PG may be a promising sustained drug delivery system with excellent therapeutic effect on glioma and hepatocellular carcinoma.

Role of WNT Agonists, BMP and VEGF Antagonists in Rescuing Osteoarthritic Knee Cartilage in a Rat Model.

The superficial zone of articular cartilage (AC) is vital for its function and biomechanics. The damaged AC gets vascularized and undergoes hypertrophy and ossification. Studies have highlighted these two as the major causative factors in osteoarthritis (OA). We aimed at preventing the OA progression in a rat knee instability model by inhibiting the vascular ingrowth and ossification using VEGF and BMP antagonist. A WNT agonist was also used to promote AC regeneration because of its protective effect on the superficial layer. Rat knee OA was created by surgical excision of the medial meniscus and medial collateral ligament. Forty rats were divided into two groups of twenty each for surgical control and tests (surgery + intra-articular injection of drugs every two weeks). Ten animals from each group were sacrificed at four and eight weeks. Histology was mainly used to evaluate the outcome. A surgical OA model was successfully created with higher histological scores for operated knees, both in short- (P = 0.0001) and long-term (P = 0.001). Modified Mankin score was lesser in the test animals as compared to control (P = 0.17) in the short-term, but the trend was reversed in the long-term (P = 0.13). Subgroup analysis revealed that repeated injections in the anterolateral compartment contributed to higher scores in the lateral (P = 0.03) and anterior (P = 0.03) compartment of the knee in the long-term. The combinatorial approach was effective in controlling the OA in short-term. Further studies are needed to test the sustained drug delivery system to improve the outcome.

Theoretical study of diffusional release of a dispersed solute from a hollow cylindrical polymeric matrix

An exact solution for the release kinetic of a solute from inside a hollow cylindrical polymeric matrix into an infinite medium has been developed, when the initial concentration of the solute (A) is greater than the solubility limit (Cs). A combination of analytical and numerical methods was used to calculate the solute concentration profile and the release rate. The model was developed for two different strategies: 1) the release medium is flowing through the hollow cylinder in which boundary layer may be neglected, 2) the release medium inside the hollow cylinder is stagnant and the boundary layer should be considered. The results indicated that the release profiles were close to the constant release rate after a typical burst release. Also, the release profile from a solid cylindrical matrix and a hollow cylinder was compared. The results indicated that the hollow cylindrical matrix is a promising carrier when zero-order release is desirable. The present model demonstrates the potential of the hollow cylindrical matrix as a suitable geometry for sustained drug delivery systems.

Preparation and Physical Properties of PCL-Metoprolol Tartrate Electrospun Nanofibers as Drug Delivery System

Electrospinning is considered a promising technology for encapsulating and loading various drugs into nanofibers. Metoprolol tartrate (MPT), hydrophilic therapy, was used as model drug. Metoprolol tartrate was loaded into poly(ɛ-caprolactone) (PCL) via blend and emulsion electospinning. The preparation processes, morphology, chemical structure thermal properties were evaluated. FESEM showed that emulsion electospinning produce larger fiber diameters(301.775nm) when compared to fibers produced by blend electrospinning(112.463, 249.34)nm, the PCL/ span 80 and MPT-PCL by emulsion method which have high fiber diameter than pure PCL and MPT-PCL by blend method and the Tm of pure PCL nanofibers and all drug loaded scaffolds are around 60°C from DSC test, water contact angle to pure PCL electrospun mats hydrophobic character (126.2°), while PCL/span 80, and PCL-drug nanofiber mats showed hydrophilic character. Our study demonstrated the possibility of using electrospinning with a promising good potential toward sustained and controlled drug delivery system.

Biocompatible thermo-responsive N-vinylcaprolactam based hydrogels for controlled drug delivery systems

The treatment of several diseases requires drugs commonly administered orally or intravenously. Said administration has several drawbacks, such as low control of the necessary drug levels in plasma, making the treatment ineffective and, furthermore, side effects and low compatibility with the patient. Recently, the use of stimuli-responsive hydrogels in controlled Drug Delivery Systems (DDSs) has been considered an excellent alternative because of its inherent biocompatibility, responsiveness to physiological changes in the body, and diversity of both natural and synthetic material options. The present work focuses mainly on the synthesis, characterization, and drug release capacity of poly (N-vinyl caprolactam) (PVCL) and poly (N-vinyl caprolactam) microgels crosslinked with various concentrations of poly (ethylene glycol) diacrylate (PEGDA), which show temperature stimuli-responsiveness near the physiological temperature of the human body. For that reason, changes in the average hydrodynamic particle diameter at different temperatures are estimated and correlated with the drug release rate. The model drug chosen for releasing studies is colchicine, a potential drug for gout disease treatment, currently in disuse because of its low therapeutic index. It is expected that the use of the control release procedure by drug encapsulation in this polymer overcomes this drawback. The synthesis of PVCL homopolymer and three VCL-co-PEGDA hydrogels varying the PEGDA crosslinker concentration was successfully carried out by emulsion polymerization. Their characterization was performed by DLS and FTIR spectroscopy. Polymerization yields were estimated by total solids analysis, and UV-VIS determined the cloud points. Finally, the drug loading and release over time were monitored by HPLC and UV-VIS spectroscopy showing that drug release profiles obtained corresponded to a sustained drug delivery system.

Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines.

Cancer vaccines represent among the most promising strategies in the battle against cancers. However, the clinical efficacy of current cancer vaccines is largely limited by the lack of optimized delivery systems to generate strong and persistent antitumor immune responses. Moreover, most cancer vaccines require multiple injections to boost the immune responses, leading to poor patient compliance. Controlled-release drug delivery systems are able to address these issues by presenting drugs in a controlled spatiotemporal manner, which allows co-delivery of multiple drugs, reduction of dosing frequency and avoidance of significant systemic toxicities. In this review, we outline the recent progress in cancer vaccines including subunit vaccines, genetic vaccines, dendritic cell-based vaccines, tumor cell-based vaccines and in situ vaccines. Furthermore, we highlight the efforts and challenges of controlled or sustained release drug delivery systems (e.g., microparticles, scaffolds, injectable gels, and microneedles) in ameliorating the safety, effectiveness and operability of cancer vaccines. Finally, we briefly discuss the correlations of vaccine release kinetics and the immune responses to enlighten the rational design of the next-generation platforms for cancer therapy.

Mucoadhesive microspheres of glutaraldehyde crosslinked mucilage of Isabgol husk for sustained release of gliclazide

Mucoadhesive microspheres have their own significant amongst the various sustained release drug delivery systems. The prolonged residence time of these delivery devices at drug absorption site results in steep concentration gradient and enhanced bioavailability. In this study, the mucilage of Isabgol husk was applied as polymeric backbone to develop gliclazide loaded microspheres by crosslinking with glutaraldehyde. The formulations were studied for surface morphology, swelling behavior, particle size, in vitro release, release kinetics, in vitro mucoadhesion and gamma scintigraphy in rabbits. The release of gliclazide from microspheres was controlled by swelling of crosslinked microspheres followed by diffusion. Gamma scintigraphic images acquired for microspheres retention in (GIT) of rabbits indicated the residence of formulation upto 24 h after oral administration. Gliclazide retained its integrity in polymeric matrix of microspheres as observed by Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometry. The sustained release of gliclazide and prolonged retention of microspheres in gastrointestinal track disclosed the rationality of mucoadhesive Isabgol husk microspheres in controlling the hyperglycemia in diabetes.

Development and evaluation of dexamethasone loaded cubosomes for the treatment of vitiligo

Liquid crystalline nanoparticles (Cubosomes) are unique structures for the effective delivery of many pharmaceutical drugs. The present study is aimed to develop and characterize novel cubosomal formulation containing dexamethasone (DMS). The cubosomes were incorporated into hydrogel for prolonged delivery of DMS to treat vitiligo. The cubosomes were prepared via top-down technique using different concentrations of glyceryl monooleate (GMO) (lipid phase), poloxamer 407 (P 407) (non-ionic surfactant), oleic acid (fatty acid) and water (aqueous phase). The formulated cubosomal formulations were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta size analyzer for their surface morphology, particle size and zeta potential. Further, they were evaluated for % entrapment efficiency and in-vitro drug release. The optimized F-12 formulation exhibited a particle size of 250.40 nm and a zeta potential of −36.10 ± 2.56 mV. The in-vitro drug release of 88.12% was achieved at 12th h. The F-12 formulation was incorporated into 1% carbopol 940 to form cubogel (CG). The F-12 loaded CG was evaluated for physical characteristics, pH, drug content, viscosity, spreadability, and in-vitro drug release studies. All the evaluation parameters for the CG formulation were said to be within the standard limits. The in-vitro drug release for DMS loaded CG was found to be 83.58% at end of 12 h, thus indicating its potential as a better sustained drug delivery system for vitiligo.

Sustained and targeted delivery of siRNA/DP7-C nanoparticles from injectable thermosensitive hydrogel for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers in humans. The inhibition of peptidyl‐prolyl cis/trans isomerase (Pin1) gene expression may have great potential in the treatment of HCC. N‐Acetylgalactosamine (GalNAc) was used to target the liver. Cholesterol‐modified antimicrobial peptide DP7 (DP7‐C) acts as a carrier, the GalNAc‐siRNA/DP7‐C complex increases the uptake of GalNAc‐siRNA and the escape of endosomes in hepatocytes. In addition, DP7‐C nanoparticles and hydrogel‐assisted GalNAc‐Pin1 siRNA delivery can effectively enhance the stability and prolong the silencing effects of Pin1 siRNA. In an orthotopic liver cancer model, the GalNAc‐Pin1 siRNA/DP7‐C/hydrogel complex can potentially regulate Pin1 expression in hepatocellular carcinoma cells and effectively inhibit tumor progression. Our study proves that Pin1 siRNA is an efficient method for the treatment of HCC and provides a sustainable and effective drug delivery system for the suppression of liver cancer.

A double-layer hydrogel based on alginate-carboxymethyl cellulose and synthetic polymer as sustained drug delivery system

A new double-layer, pH-sensitive, composite hydrogel sustained-release system based on polysaccharides and synthetic polymers with combined functions of different inner/outer hydrogels was prepared. The polysaccharides inner core based on sodium alginate (SA) and carboxymethyl cellulose (CMC), was formed by physical crosslinking with pH-sensitive property. The synthetic polymer out-layer with enhanced stability was introduced by chemical crosslinking to eliminate the expansion of inner core and the diffusion of inner content. The physicochemical structure of the double-layer hydrogels was characterized. The drug-release results demonstrated that the sustained-release effect of the hydrogels for different model drugs could be regulated by changing the composition or thickness of the hydrogel layer. The significant sustained-release effect for BSA and indomethacin indicated that the bilayer hydrogel can be developed into a novel sustained delivery system for bioactive substance or drugs with potential applications in drugs and functional foods.

Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research.

Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution–gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.

The Role of Matrix Tablet in Oral Drug Delivery System

Matrix tablet is an important tool for controlled and sustained release dosage forms. The important route of drug administered by oral route. The oral dosage forms developed and improvedthe patient compliance. The oral controlled release system has been developed by change to formulation scientist, due to the inability to restrain and localized of a system at target area of the gastrointestinal tract. The hydrophilic polymers are becomes product of choice for important ingredients formulation of sustained release dosage forms.The benefit of sustained release dosage forms are compared to the conventional dosage forms and uniform therapeutic effects and drug plasma concentration. The matrices used of various class of hydrophilic, hydrophobic, mineral or biodegradabletypes of polymers and their degradation product have been focused. The drug have less half-life and eliminated from the body with in short period of time. The formulation of drug matrix types have been avoided by difficult sustained release drug delivery system. The mechanism of matrix tablets include the both dissolution and diffusion controlled. It produce the therapeutic efficacy. The goal of this review article is to discuss the release mechanism of the drug dosage form of various polymers and a matrix system used in preparation of matrix tablets.

A New Bevacizumab Carrier for Intravitreal Administration: Focus on Stability.

Bevacizumab (BVZ) is a monoclonal antibody that binds to human vascular endothelial growth factor A (VEGF-A) and inhibits the interaction between VEGF-A and VEGF receptors, thus blocking the angiogenesis. Repeated intravitreal injections of BVZ for the treatment of ocular pathologies that present an excessive proliferation results in a low patience compliance. BVZ is specially indicated for the treatment of diabetic and degenerative retinopathy. In the present study, we designed lipid nanoparticles (NPs) as a BVZ sustained drug delivery system for reducing the frequency of administration. We used a simple and highly efficient procedure, “Cold dilution of microemulsions”, to obtain spherical NPs with mean diameters of 280–430 nm, Zeta potentials between −17 and −31 mV, and drug entrapment efficiencies between 50 to 90%. This study focused on the biochemical and biophysical stabilities of BVZ after entrapment in NPs. SDS-PAGE electrophoretic analysis and circular dichroism, dynamic light scattering, and scanning electron microscopy were used to characterize BVZ-loaded NPs. The biocompatibility was assessed by in vitro cell compatibility studies using the ARPE-19 cell line. Thus, in this work, a stable BVZ-loaded system was obtained. In addition, several studies have shown that BVZ is released slowly from the lipid matrix and that this system is biocompatible. The results are promising and the developed NPs could be exploited to create a new, potentially effective and minimally invasive treatment of intraocular diseases.

A Novel Approach on Role of Polymers Used In Sustained Release Drug Delivery System- A Review

A Novel Approach on Role of Polymers Used In Sustained Release Drug Delivery System- A Review

Rapid Electrochemical Quantification for In Vitro Release Trait of Ophthalmic Drug Loaded within Mucoadhesive Metal Organic Framework (MOF)

AbstractLimited residence time of drugs in the ocular surface, poor bioavailability and side effects are the major challenges in ophthalmic treatment. From the last decade, the pharmaceutical industry is in search of a reliable ophthalmic drug delivery system. In the present study, we demonstrate amine‐functionalized mucoadhesive MIL88B(FeMOF) as a drug delivery cargo to encapsulate ophthalmic drug Timolol (TM) at a rate of 195 μg/mg. Invitro release of TM (only upto 63 %) from loaded FeMOF (TM@FeMOF) within 10 h without burst effect was a noticeable feature that anticipates enhanced preocular retention by the sustained release of TM through extensive H‐bonding of the amine group of MOFs with mucin. A novel and facile approach using Differential Pulse Voltammetry (DPV) were harnessed for rapid quantification of TM during in‐vitro release studies, further validated by HPLC measurement(<10 % deviation). The encouraging results from in‐vitro studies forecast the success story of TM@FeMOF as a biocompatible, biodegradable, and sustainable ophthalmic drug delivery system.

Potential of Exosomes for Diagnosis and Treatment of Joint Disease: Towards a Point-of-Care Therapy for Osteoarthritis of the Knee.

In the knee joint, articular cartilage injury can often lead to osteoarthritis of the knee (OAK). Currently, no point-of-care treatment can completely address OAK symptoms and regenerate articular cartilage to restore original functions. While various cell-based therapies are being developed to address OAK, exosomes containing various components derived from their cells of origin have attracted attention as a cell-free alternative. The potential for exosomes as a novel point-of-care treatment for OAK has been studied extensively, especially in the context of intra-articular treatments. Specific exosomal microRNAs have been identified as possibly effective in treating cartilage defects. Additionally, exosomes have been studied as biomarkers through their differences in body fluid composition between joint disease patients and healthy subjects. Exosomes themselves can be utilized as a drug delivery system through their manipulation and encapsulation of specific contents to be delivered to specific cells. Through the combination of exosomes with tissue engineering, novel sustained release drug delivery systems are being developed. On the other hand, many of the functions and activities of exosomes are unknown and challenges remain for clinical applications. In this review, the possibilities of intra-articular treatments utilizing exosomes and the challenges in using exosomes in therapy are discussed.

A carboxymethyl lentinan layer by layer self-assembly system as a promising drug chemotherapeutic platform

Surface functionalization of mesoporous silica nanoparticles (MSNs) has been proposed as an efficient strategy for enhancing the biocompatibility and efficiency of an MSN-based carrier platform. Herein, natural polyelectrolyte multilayers composed of poly-l-ornithine (PLO) and carboxymethyl lentinan (LC) were coated on the surface of MSNs through a layer-by-layer (LbL) self-assembly technique, and were characterized by ζ-potential, FTIR, 13C NMR, SEM, TEM, XRD, and TG. The prepared carrier presented alternating positive and negative potentials when coated with the polyelectrolytes, and the surface of MSN-PLO/LC was rougher compared to the naked MSNs. The biocompatibility tests, including cytocompatibility, hemocompatibility, and histocompatibility, showed that MSNs biocompatibility could be improved by modifying LC. A high loading and sustained release drug delivery system was constructed after loading doxorubicin (DOX) into the prepared MSN-PLO/LC, which exhibited significant anti-proliferative efficiency in human cervical cancer cell lines (Hela). Therefore, the PLO/LC LbL NPs (layer-by-layer self-assembled nanoparticles coated with PLO/LC layers) based on MSNs, which is easily prepared by electrostatic interactions, can be considered a promising drug chemotherapeutic platform and delivery technique for future human cervical cancer therapy.

Synthesis and characterization of hydrogels based on carboxymethyl chitosan and poly(vinylpyrrolidone) blends prepared by electron beam irradiation having anticancer efficacy, and applications as drug carrier for controlled release of drug

Herein, carboxymethyl chitosan and poly(vinylpyrrolidone) based hydrogels were synthesized by electron beam irradiation with dose variations (15 kGy, 30 kGy, and 45 kGy) for drug delivery applications. Irradiation crosslinked hydrogels were characterized for swellings in different medias, chemical, thermal, cell cytotoxicity, and drug release aspects. Swelling analysis was evaluated in distilled water, buffer, and saline solutions. Fourier transform infrared analysis revealed the establishment of physical interactions and confirmed the presence of functional groups present in the drug carriers. Scanning electron microscopy depicted the porous structure, which is responsible for swelling, drug loading, and release. Cell cytotoxicity assays indicated good cell viability on RAW 264.7 cells and anticancer activity on cancerous AGS cell lines. Cumulative drug release (%) of kanamycin in PBS at pH 7.4 was more than 90 % at 168 h. These drug carriers show promise to be developed as a sustained drug delivery system.

Sustained-release drug delivery systems for the treatment of glaucoma.

Glaucoma, a leading cause of irreversible blindness, affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection. Although topical therapies are often effective when used as prescribed, the drawbacks of current medical management methods include poor patient adherence, local and systemic side effects, and in some cases, limited therapeutic efficacy. Novel ocular drug delivery platforms promise to deliver differentiated drug formulations with targeted delivery leveraging patient-independent administration. Several platforms are in various stages of development with promising pre-clinical and clinical data. The Bimatoprost Sustained Release (SR) intracameral implant was approved in the United States in March of 2020, making it the first long-term injectable therapy available for the treatment of glaucoma. This review aims to provide an update on novel sustained release drug delivery systems that are available today as well as those that might be commercialized in coming years.

Electrospinning, Preparation and Characterization of Polyvinylidene Fluoride / Pectin Electrospun Loaded with Benzalkonium Chloride as a Drug Reservoirs

Porous nanofiber electrospun of polyvinylidene fluoride (PVDF)/pectin was successfully developed using electrospinning method containing benzalkonium chloride (BAC) as a drug model for the controlled drug delivery system assessment. The electrospun was tested for its mechanical, morphological, and wettability properties. Scanning electron microscope (SEM) micrograph demonstrated that the smooth surfaces of nanofibers morphology had achieved up to 2 wt% pectin inclusion with optimum fiber diameter, 143 ± 1.4 nm. The optimized scaffold PVDF/Pectin showed that the reduction of mechanical integrity and the optimum value of tensile strength, modulus strength, and elongation at break were 5.98 ± 0.17 MPa, 16.82 ± 0.10 MPa, and 79.3 ± 1.3% MPa. Water contact angle analysis and degree of swelling suggested that the inclusion of pectin had enhanced the wettability properties of hydrophobic PVDF electrospun with the highest swelling capacity achieved of 78.9 ± 1.7%. The in vitro drug release tests using BAC, which was released from the hybrid electrospun nanofibers, achieved prolonged release profile due to the elimination of the uncontrollable initial burst release. Kinetic release study from Higuchi Model and Korsmeyer-Peppas further validates that the drug release mechanism is only influenced by the diffusion factor. The present study indicates the potential of PVDF/pectin electrospun nanofibers to be exploited as a tool for a sustainable drug delivery system.