Drug Delivery System For Administration Research Articles

The Comprehensive Review: Exploring Future Potential of Nasopulmonary Drug Delivery Systems for Nasal Route Drug Administration

This comprehensive review aims to explore the future potential of nasopulmonary drug delivery systems for the administration of drugs through the nasal route. Nasal drug delivery has gained significant attention due to its numerous advantages, including rapid absorption, avoidance of first-pass metabolism, and non-invasive administration. This review provides an overview of the nasal anatomy and physiology, highlighting the factors influencing drug absorption and bioavailability. Additionally, it discusses the various types of nasopulmonary drug delivery systems, such as nasal sprays, powders, and gels, along with their advantages and limitations. Furthermore, the review delves into the challenges associated with nasal drug delivery, including mucociliary clearance, nasal irritation, and formulation issues. The potential applications of nasopulmonary drug delivery systems in the treatment of various diseases, such as allergies, respiratory disorders, and systemic conditions, are also discussed. Finally, the review concludes with an outlook on the future prospects of nasopulmonary drug delivery systems, emphasising the need for further research and development to optimise their efficacy and safety.
 Keywords: nasal pulmonary; nasal spray; nasal mucosa; gels; drops; nasal approaches; nasal route; nasal delivery.

Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies

Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose,improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of −20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC0–24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.

Oral Modified Drug Release Solid Dosage Form with Special Reference to Design; An Overview.

Oral drug delivery is the most widely utilized route of administration among all the routes that have been explored for systemic delivery of drugs via pharmaceutical products of different dosage form and this oral route provides maximum active surface area among all drug delivery system for administration of various drugs. The attractiveness of these dosage forms is due to awareness of toxicity and ineffectiveness of drugs when administered by oral conventional method in the form of tablets and capsules. Usually, conventional dosage form produces wide range of fluctuation in drug concentration in the bloodstream and tissues with consequent undesirable toxicity and poor efficiency. The maintenance of concentration of drug in plasma within therapeutic index is very critical for effective treatment. These factors as well as factors such as repetitive dosing and unpredictable absorption lead to the concept of oral modified drug delivery systems like Sustained release, prolonged release, modified release, extended release. These formulations are used to identify drug delivery systems that are designed to achieve or extend therapeutic effect by continuously releasing medication over an extended period of time after administration of a single dose. This review describes the basic information regarding modified release dosage form like designed to release their medication in controlled manner, criteria for selecting modified release dosage form and factors influencing the dosage and release pattern.

Advanced trends in protein and peptide drug delivery: a special emphasis on aquasomes and microneedles techniques.

Proteins and peptides have a great potential as therapeutic agents; they have higher efficiency and lower toxicity, compared to chemical drugs. However, their oral bioavailability is very low; also, the transdermal peptide delivery faces absorption limitations. Accordingly, most of proteins and peptides are administered by parenteral route, but there are many problems associated with this route such as patient discomfort, especially for pediatric use. Thus, it is a great challenge to develop drug delivery systems for administration of proteins and peptides by routes other than parenteral one. This review provides an overview on recent advances adopted for protein and peptide drug delivery, focusing on oral and transdermal routes. This is followed by an emphasis on two recent approaches adopted as delivery systems for protein and peptide drugs, namely aquasomes and microneedles. Aquasomes are nanoparticles fabricated from ceramics developed to enhance proteins and peptides stability, providing an adequate residence time in circulation. It consists of ceramic core coated with poly hydroxyl oligomer, on which protein and peptide drug can be adsorbed. Aquasomes preparation, characterization, and application in protein and peptide drug delivery are discussed. Microneedles are promising transdermal approach; it involves creation of micron-sized pores in the skin for enhancing the drug delivery across the skin, as their length ranged between 150 and 1500μm. Types of microneedles with different drug delivery mechanisms, characterization, and application in protein and peptide drug delivery are discussed. Graphical abstract.

HEMA based pH-sensitive semi IPN microgels for oral delivery; a rationale approach for ketoprofen

Objectives: The study aimed to develop safe, effective, and targeted drug delivery system for administration of nonsteroidal anti-inflammatory drugs (NSAIDs) in the form of microgels. We developed pH responsive microgels to overcome the mucosal damage caused by traditional immediate release dosage forms. Colon targeting and controlled release formulations have the potential to improve efficacy and reduce undesirable effects associated with NSAIDs.Methods: The pH sensitive oral hydrogel demonstrates the potential to target the colon. Cellulose acetate phthalate (CAP) and hydroxyethyl methacrylate (HEMA) based microgel particles were produced using a free radical polymerization technique using ammonium persulfate (APS) initiator and methylenebisacrylamide (MBA) as the crosslinking agent. Swelling and in-vitro drug release studies were performed at a range of pH conditions. The produced formulations were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy (SEM), and X-ray diffraction. Biocompatibility of the microgels was analyzed in cytotoxicity studies.Key findings: The swelling and release rate were negligible at pH 1.2, which confirmed the pH-responsiveness of CAP-co-poly(HEMA). The co-polymeric system prevents the release of ketoprofen sodium in the stomach owing to limited swelling at gastric pH, whilst promoting release at the basic pH observed in the colon. SEM images confirmed porous nature of the microgels that facilitate effective drug diffusion through the polymeric matrix. Cytotoxicity studies revealed biocompatibility of hydrogels.Conclusion: These investigations showed that that the controlled drug release and gastro-protective drug delivery of NSAIDS was achieved using CAP-co-poly(HEMA) microgel particles.

Effects of thermosensitive chitosan-gelatin based hydrogel containing glutathione on Cisd2-deficient chondrocytes under oxidative stress

Aging is considered as a primary risk factor in the development of osteoarthritis (OA) which associated with mitochondrial dysfunction and oxidative stress. CDGSH iron sulfur domain 2 (Cisd2) deficiency causes mitochondrial dysfunction and drive premature aging. In the present study, thermosensitive chitosan-gelatin based hydrogel containing glutathione was developed as injectable drug delivery system for administration by minimal invasive surgery for the treatment of OA. Cisd2 deficiency (Cisd2−/−) mouse induced pluripotent stem cells-derived chondrocytes were established and characterized. The results suggested that 100μM of glutathione may be an optimal concentration to treat Cisd2−/− chondrocytes without cytotoxicity. The developed hydrogel showed sustained release profile of the glutathione and could decrease the reactive oxygen species level. Post-treatment of glutathione-loaded hydrogel could rescue Cisd2−/− chondrocytes from oxidative damage via increasing catalase activity, down-regulation of inflammation, and decreasing apoptosis. These results suggest that thermosensitive glutathione-loaded hydrogel may be a potential antioxidant therapeutic strategy for treating Cisd2−/− chondrocytes in the near future.

Nanoparticle-facilitated autophagy inhibition promotes the efficacy of chemotherapeutics against breast cancer stem cells.

Cancer stem cells (CSCs) have garnered increasing attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced 'stemness' and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ)-mediated autophagy inhibition in sorted ALDH(hi) cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH(hi) MDA-MB-231cells invitro. Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH(hi) cells. More importantly, compared with single treatment, the combined delivery systems NPCQ/NPDOX and NPCQ/DOX (NPCQ/NPDTXL and NPCQ/DTXL) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs (p<0.01) in an MDA-MB-231 orthotopic tumor murine model. Therefore, our research provides new insights into the nanoparticle-facilitated combination of autophagy inhibition and chemotherapy for effective therapy of breast cancer.

A Drug Delivery System for Administration of Anti-TNF-α Antibody.

PurposeTo describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti–TNF-α antibody administration.MethodsA DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100–300 μm in diameter porosity) loaded with 10% polyvinyl alcohol hydrogel carrying 5 mg/ml (weight/volume) of anti–TNF-α antibody. Drug-loaded DDS was sterilized with 25 kGy of gamma irradiation. Long-term in vitro antibody affinity and release was evaluated at room temperature or 37°C using enzyme-linked immunosorbent assay (ELISA) and protein fluorescence. In vivo clinical and histolopathological assessment was performed by subcutaneous implantation in BALB/c mice for 3 months.ResultsGamma irradiation, repeated dry/wet cycles, and storage at room temperature for 1 year or 37°C for 1 month had no deleterious effects on antibody affinity. Anti–TNF-α release was high during the first minutes of aqueous exposure, followed by stabilization and gradual, low-dose, antibody release over the next 30 days. Histopathologic evaluation of explanted DDS showed a fibrous pseudocapsule and a myxoid acute/chronic inflammation without granuloma formation surrounding the implants.ConclusionsSustained local delivery of anti–TNF-α antibody is feasible using the described DDS, which provides stability of the enclosed antibody for up to 1 year of storage. Preliminary results show good in vivo tolerance following subcutaneous placement for 3 months. The proposed fabrication and sterilization process opens new possibilities for the delivery of biologic agents to the anterior surface of the eye.Translational RelevanceThe described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy.

ORAL CONTROLLED RELEASE DRUG DELIVERY SYSTEM: AN OVERVIEW

Oral drug delivery is the most preferred and con venient option as the oral route provides maximum active surface area among all drug delivery system for administration of various drugs. The attractiveness of these dosage forms is due to awareness to toxicity and ineffectiveness of drugs when administere d by oral conventional method in the form of tablets and capsules. Usually conventional dosage form produces wide range of fluctuation in drug concentration in the bloodstream and tissues with consequent undesirable toxicity and poor efficiency. The mainte nance of concentration of drug in plasma within therapeutic index is very critical for effective treatment. These factors as well as factors such as repetitive dosing and unpredictable absorption lead to the concept of oral controlled release drug delivery systems. Controlled release drug delivery system works on many different mechanisms to control the release rate of drugs. Various mechanisms like osmotic pressure, matrix system, reservoir system, altered density system etc. have been utilized as formulat ion approaches. The present article contains brief review on various formulation approaches for controlled release drug delivery system.

Preparation and evaluation of bioactive and compatible starch based superabsorbent for oral drug delivery systems

Novel types of highly swelling hydrogels (superabsorbent) were prepared by grafting crosslinked poly acrylic acid-co-2-hydroxyethylmetacrylate (PAA-co-HEMA) chains onto starch through a free radical polymerization method. The effect of grafting variables (i.e., concentration of methylenebisacrylamide (MBA), acrylic acid/2-hydroxy methymetacrylate (AA/HEMA) weight ratio, ammonium persulfate (APS), starch, neutralization percent, were systematically optimized to achieve a hydrogel with a maximum swelling capacity. The superabsorbent (SAP) formation was confirmed by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The controlled-release behavior of diclofenac sodium (DS) from SAP was investigated and showed that the release profiles of DS from superabsorbent polymer were slow (less than 6 %) in simulated gastric fluid (SGF, pH1.6) over 3h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH7.4) within 8h after changing media. Overall, the results demonstrated that biodegradable superabsorbent could successfully deliver a drug to the intestine without losing the drug in the stomach, and could be potential candidates for an orally administrated drug delivery system.

Novel nano-porous hydrogel as a carrier matrix for oral delivery of tetracycline hydrochloride

A novel nano-porous hydrogel (NPH) was synthesized via graft copolymerization of sodium acrylate (Na-AA) and acrylamide (AAm) onto salep backbones and its application as a carrier matrix for oral delivery of tetracycline hydrochloride (TH) was investigated. The Taguchi method as a strong experimental design tool was used for synthesis optimization. The swelling behavior of optimum hydrogel was measured in various media. The hydrogel formation was confirmed by Fourier transform infrared spectroscopy (FT-IR) and thermogravimetrical analysis (TGA). The study of the surface morphology of the hydrogels using SEM and AFM showed a nanoporous (average pore size: 180 nm) structure for the sample obtained under optimized conditions. The drug delivery results demonstrated that this NPH could successfully deliver a drug to the intestine without losing the drug in the stomach, and could be a good candidate as an orally administrated drug delivery system.

UV-prepared salep-based nanoporous hydrogel for controlled release of tetracycline hydrochloride in colon

A highly swelling nanoporous hydrogel (NPH) was synthesized via UV-irradiation graft copolymerization of acrylic acid (AA) onto salep backbone and its application as a carrier matrix for colonic delivery of tetracycline hydrochloride (TH) was investigated. Optimized synthesis of the hydrogel was performed by the classic method. The swelling behavior of optimum hydrogel was measured in different media. The hydrogel formation was confirmed by Fourier transform infrared spectroscopy (FTIR) and thermo-gravimetric analysis (TGA/DTG/DTA). The study of the surface morphology of hydrogels using SEM showed a nanoporous (average pore size: about 350 nm) structure for the sample obtained under optimized conditions. The drug delivery results demonstrated that this NPH could successfully deliver a drug to the colon without losing the drug in the stomach, and could be a good candidate as an orally administrated drug delivery system.

Alginate‐based biodegradable superabsorbents as candidates for diclofenac sodium delivery systems

AbstractNovel types of highly swelling hydrogels were prepared by grafting crosslinked polyacrylamide‐co‐poly‐2‐acrylamido‐2‐methylpropane sulfonic acid (PAAm‐co‐PAMPS) chains onto sodium alginate (Na‐Alg) through a free radical polymerization method. The superabsorbent formation was confirmed by Fourier transform infrared spectroscopic (FTIR). The controlled release behavior of diclofenac sodium (DS) from superabsorbent polymer was factinvestigated, and shown that the release profiles of DS from superabsorbent polymer were slow in simulated gastric fluid (SGF, pH 1.2) over 3 h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 7.4) within 21 h after changing media. Overall the results demonstrated that biodegradable superabsorbent could successfully deliver a drug to the intestine without losing the drug in the stomach, and could be potential candidates as an orally administrated drug delivery system. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Synthesis and Evaluation of pH and Thermosensitive Pectin‐Based Superabsorbent Hydrogel for Oral Drug Delivery Systems

AbstractThe purpose of this study was to produce intelligent pectin‐based superabsorbent polymers (SAP) to be used as pH‐ and thermosensitive carriers for the controlled delivery of non‐steroidal anti‐inflammatory drugs (NSAIDs). The superabsorbent formation was confirmed by Fourier transform infrared spectroscopic (FT‐IR) and scanning electron microscopy (SEM).The effects of pH, ionic strength, temperature, porosity, particle size and levels of loaded drug on drug release profile in various surrounding media were investigated. Each sample was well characterized through swelling studies. The molecular weight between crosslinks $\displaystyle (\overline {{\tf="PS_HENI"M}}_C) $, crosslinking density (ve) polymer–solvent interaction parameter (χ), and the shear modulus of the superabsorbents (G) were calculated. The results revealed that the release profiles of IBU from the superabsorbent polymer were low (lower than 14%) in simulated gastric fluid (SGF, pH 1.2) over 3 h, but nearly all of the initial drug content (more than 79%) was released in simulated intestinal fluid (SIF, pH 7.4) within 6 h after changing media. Overall the results demonstrated that biodegradable superabsorbents could successfully deliver a drug to the intestine without losing the drug in the stomach, and could be potential candidates for an orally administrated drug delivery system.

Smart Pectin‐based Superabsorbent Hydrogel as a Matrix for Ibuprofen as an Oral Non‐steroidal Anti‐inflammatory Drug Delivery

AbstractThe purpose of this study was to produce an intelligent superabsorbent polymer (SAP) to be used as a pH sensitive matrix for the controlled delivery of drugs. Novel types of highly swelling SAPs were prepared by grafting crosslinked acrylic acid‐co‐acrylamide (AA‐co‐AAm) chains onto pectin by free‐radical polymerization. The superabsorbent formation was confirmed by Fourier transform infrared spectroscopic (FT‐IR) and scanning electron microscopy (SEM). The controlled release behavior of ibuprofen (IBU) from the superabsorbent polymer was investigated. SAP structural‐property relationships that affect its controlled release behavior were determined. Analysis of the results indicated that it is possible to optimize ibuprofen (IBU) controlled release by adjusting the SAP composition and the crosslinking degree of the copolymer. The results revealed that the release profiles of IBU from the superabsorbent polymer were slow (lower than 2%) in simulated gastric fluid (SGF, pH 1.2) over 3 h, but nearly all of the initial drug content (more than 84%) was released in simulated intestinal fluid (SIF, pH 7.4) within 85 h after changing media. Overall the results demonstrated that biodegradable superabsorbents could successfully deliver a drug to the intestine without losing the drug in the stomach, and could be potential candidates as an orally administrated drug delivery system.

Immunological Risk of Injectable Drug Delivery Systems

Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications are associated with administration of DDS. These immunological events can compromise the efficacy and safety of these systems by changing the pharmacokinetics, biodistribution and targeting capability of DDS, and by inducing hypersensitivity reactions. Antibodies induced by administration of DDS can be directed against the carrier material, the drug and/or targeting ligands associated with the DDS. Complement activation and opsonization of DDS, which may or may not be associated with antibody formation, may lead to accelerated clearance, hypersensitivity reactions and formation of membrane attack complexes resulting in premature release of the drug. Also platelets have been reported to play a role in DDS immunogenicity. Despite our curtailed understanding of the relationships between physicochemical characteristics and immunogenicity of DDS, several risk factors have been identified. Insight into these factors should be employed in the development of novel DDS with low immunological risk.

Induction of immune tolerance by oral administration of drug delivery system “antigen plus immunosuppressant”

Induction of immune tolerance by oral administration of drug delivery system “antigen plus immunosuppressant”

Induction of immune tolerance by oral administration of drug delivery system “antigen plus immunosuppressant”

Induction of immune tolerance by oral administration of drug delivery system “antigen plus immunosuppressant”