Improved Drug Loading Capacity Research Articles

Recent Advances in Development of Vesicular Carrier for Transdermal Drug Delivery: A Review

Transdermal drug delivery has gained significant attention as a non-invasive and convenient method for administering drugs. However, the stratum corneum, the outermost layer of the skin, poses a significant barrier to drug permeation. To overcome this challenge, vesicular carriers have emerged as promising systems for enhancing drug delivery through the skin. This review highlights recent advances in the development of vesicular carriers for transdermal drug delivery. Liposomes, niosomes, transfersomes, ethosomes, and solid lipid nanoparticles are among the commonly used vesicular carriers. These carriers offer advantages such as improved drug solubility, prolonged drug release, and enhanced drug stability. Additionally, they can encapsulate a wide range of drugs, including hydrophilic and lipophilic compounds. Various strategies have been employed to optimize vesicular carriers for transdermal drug delivery. These include modifying the vesicle composition, size, and surface charge to enhance skin penetration. The incorporation of penetration enhancers, such as surfactants, has also been explored to improve drug permeation across the skin. Furthermore, advancements in nanotechnology have led to the development of novel vesicular carriers, such as nanostructured lipid carriers and elastic liposomes. These carriers offer improved drug loading capacity, sustained release profiles, and enhanced skin penetration. Moreover, the use of vesicular carriers has shown promise in delivering a wide range of therapeutic agents, including small molecules, peptides, proteins, and genetic material. The ability to encapsulate and deliver these diverse drug entities opens new possibilities for transdermal drug delivery in various therapeutic areas.

TPGS/soluplus® blended micelles: an effective strategy for improving loading capacity of ferroptosis inducer erastin

Erastin is the most classical small molecular ferroptosis inducer but its clinical application is hindered due to its poor solubility. Nanotechnology has been used to improve ferroptosis inducer erastin’s solubility. The recently reported erastin-incorporated nanosystems (e.g., nanoparticulate ferritin, poly(ethylene glycol) methyl ether-blockpoly(lactide-co-glycolide) (mPEG-PLGA) nanoparticle, exosome, and liposome) could to some degree elevate its solubility, but were still poor in loading capacity. To be specific, the maximum entrapment efficiency and drug loading in previous studies were approximately 36% and 3.7%, respectively. In order to improve drug loading capacity, we constructed a novel carrier based on Vitamin E d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) blended micelles. The erastin@TPGS/Soluplus® micelles were prepared by thin film hydration method, and formulation details including dosage of Soluplus®, the weight ratio of TPGS to Soluplus®, the weight ratio of erastin to TPGS/Soluplus® were optimized. The physicochemical properties of the erastin micelles were measured by DLS, TEM, FTIR, and TG-DSC analysis. The products exhibited a nanoscale and uniform particle size (78.11 ± 0.54 nm) and neutral surface charge (-0.43 ± 0.32 mV). Significantly improved entrapment efficiency (89.63 ± 1.81%) and drug loading rate (10.03 ± 0.14%) were obtained, which was over 2-fold of current reports. The in vitro release study demonstrated that erastin could release in a sustained yet complete manner, and the drug release might be governed by multiple mechanisms including anomalous diffusion of non-Fickian diffusion, matrix erosion and sustained release. In summary, this proposed erastin nanosystem provides a new strategy for improving loading capacity, and may probably augment ferroptosis-inducing therapy for cancer treatment.

A universal powder-laden crosslinked chitosan microneedle patch for high-dose controllable drug delivery

In this study, we constructed a novel powder-laden core–shell crosslinked chitosan microneedle patch for high-dose and controllable delivery of various drugs, including both macromolecular biological drugs and small-molecule chemical drugs. Direct loading of drug powders greatly improved drug loading capacity and minimized degradation. The results of the in vitro drug release study suggested that the release behaviors of the most tested drugs (both macromolecular drugs and small-molecule drugs) can be tuned by adjusting the crosslink density of the microneedle shell to achieve either rapid or sustained release of the loaded drug. The in vivo hypoglycemic efficacy test in streptozotocin-induced diabetic mice further proved that the onset and duration of the insulin-laden patch can be customized by adjusting the crosslink density. Furthermore, a combination of microneedle patches with different crosslink densities not only rapidly reduced blood glucose levels to normoglycemic levels (within 1 h) but also maintained normoglycemia for up to 36 h. The insulin loaded in the patch also showed good stability during storage at 40 °C for 6 months. Our results suggest that this powder-laden patch represents a strong candidate for addressing the multiple challenges in the preparation and application of polymeric microneedles and shows promise in clinical applications.

Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment

This review evaluates the literature on nanoparticle-based drug delivery systems for cancer treatment and assesses their efficacy. Nanoparticles have shown potential for improving anticancer agent delivery, reducing systemic toxicity, and enhancing therapeutic outcomes. Extensive studies have shown promising results in preclinical and clinical trials. However, challenges such as limited drug loading capacity, stability issues, and potential side effects need to be addressed to enhance clinical translation. Researchers are exploring strategies to improve drug loading capacity, such as modifying nanoparticle surfaces or developing novel drug encapsulation techniques. By increasing drug loading, the therapeutic efficacy of these systems can be significantly enhanced. Stability issues also pose a hurdle in clinical translation. To overcome stability issues, researchers are investigating methods to enhance the stability of nanoparticles, such as using protective coatings or optimising the formulation. Additionally, efforts are being made to minimise potential side effects by carefully selecting biocompatible materials for nanoparticle synthesis and conducting rigorous toxicity studies before moving forward with clinical trials.

Amelioration of Cancer Employing Chitosan, Its Derivatives, and Chitosan-Based Nanoparticles: Recent Updates.

The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility. The characteristics of chitosan and its chemically tailored derivatives, as well as their use in cancer therapy, will be examined in this review.

Ligand Installation to Polymeric Micelles for Pediatric Brain Tumor Targeting.

Medulloblastoma is a life-threatening disease with poor therapeutic outcomes. In chemotherapy, low drug accumulation has been a cause of these outcomes. Such inadequate response to treatments has been associated with low drug accumulation, particularly with a limited cellular uptake of drugs. Recently, the conjugation of drugs to ligand molecules with high affinity to tumor cells has attracted much attention for enhancing drug internalization into target cells. Moreover, combining tumor-targeting ligands with nano-scaled drug carriers can potentially improve drug loading capacity and the versatility of the delivery. Herein, we focused on the possibility of targeting CD276/B7-H3, which is highly expressed on the medulloblastoma cell membrane, as a strategy for enhancing the cellular uptake of ligand-installed nanocarriers. Thus, anti-CD276 antibodies were conjugated on the surface of model nanocarriers based on polyion complex micelles (PIC/m) via click chemistry. The results showed that the anti-CD276 antibody-installed PIC/m improved intracellular delivery into CD276-expressing medulloblastoma cells in a CD276-dependent manner. Moreover, increasing the number of antibodies on the surface of micelles improved the cellular uptake efficiency. These observations indicate the potential of anti-CD276 antibody-installed nanocarriers for promoting drug delivery in medulloblastoma.

Macrocyclic Supramolecular Assemblies Based on Hyaluronic Acid and Their Biological Applications.

Hyaluronic acid (HA), which contains multiple carboxyl, hydroxyl, and acetylamino groups and is an agent that targets tumors, has drawn great attention in supramolecular diagnosis and treatment research. It can not only assemble directly with macrocyclic host-guest complexes through hydrogen bonding and electrostatic interactions but also can be modified with macrocyclic compounds or functional guest molecules by an amidation reaction and used for further assembly. Macrocycles play a main role in the construction of supramolecular drug carriers, targeted imaging agents, and hydrogels, such as cyclodextrins and cucurbit[n]urils, which can encapsulate photosensitizers, drugs, or other functional guest molecules via host-guest interactions. Therefore, the formed supramolecular assemblies can respond to various stimuli, such as enzymes, light, electricity, and magnetism for controlled drug delivery, enhance the luminescence intensity of the assembly, and improve drug loading capacity. In addition, the nanosupramolecular assembly formed with HA can also improve the biocompatibility of drugs, reduce drug toxicity and side effects, and enhance cell permeability; thus, the assembly has extensive application value in biomedical research. This Account mainly focuses on macrocyclic supramolecular assemblies based on HA, especially their biological applications and progress in the field, and these assemblies include (i) guest-modified HA, such as pyridinium-, adamantane-, peptide-, and other functional-group-modified HA, along with their cyclodextrin and cucurbit[n]uril assemblies; (ii) macrocycle-modified HA, such as HA modified with cyclodextrins and cucurbit[n]uril derivatives and their assembly with various guests; (iii) direct assembly between unmodified HA and cyclodextrin- or cucurbit[n]uril-based host-guest complexes. Particularly, we discussed the important role of macrocyclic host-guest complexes in HA-based supramolecular assembly, and the roles included improving the water solubility and efficacy of hydrophobic drugs, enhancing the luminescent intensity of assemblies, inducing room temperature phosphorescence and providing energy transfer systems, constructing multi-stimulus-responsive supramolecular assemblies, and in situ formation of hydrogels. Additionally, we believe that obtaining in-depth knowledge of these HA-based macrocyclic supramolecular assemblies and their biological applications encompasses many challenges regarding drug carriers, targeted imaging agents, wound healing, and biomedical soft materials and would certainly contribute to the rapid development of supramolecular diagnosis and treatment.

Recent Development of Nano-Carbon Material in Pharmaceutical Application: A Review.

Carbon nanomaterials have attracted researchers in pharmaceutical applications due to their outstanding properties and flexible dimensional structures. Carbon nanomaterials (CNMs) have electrical properties, high thermal surface area, and high cellular internalization, making them suitable for drug and gene delivery, antioxidants, bioimaging, biosensing, and tissue engineering applications. There are various types of carbon nanomaterials including graphene, carbon nanotubes, fullerenes, nanodiamond, quantum dots and many more that have interesting applications in the future. The functionalization of the carbon nanomaterial surface could modify its chemical and physical properties, as well as improve drug loading capacity, biocompatibility, suppress immune response and have the ability to direct drug delivery to the targeted site. Carbon nanomaterials could also be fabricated into composites with proteins and drugs to reduce toxicity and increase effectiveness in the pharmaceutical field. Thus, carbon nanomaterials are very effective for applications in pharmaceutical or biomedical systems. This review will demonstrate the extraordinary properties of nanocarbon materials that can be used in pharmaceutical applications.

Porous Silicon Carrier Endowed with Photothermal and Therapeutic Effects for Synergistic Wound Disinfection.

Drug carriers endowed with photothermal effects will allow the drug delivery system to release drugs in a thermal-stimuli manner. In addition, the photothermal therapy (PTT) will also interplay with therapeutic drugs loaded in the carrier to exhibit synergistic bioactivity for various disease treatment. However, endowing the drug carrier with photothermal and synergistic therapeutic effects still has challenge. Herein, we demonstrate that surface modification of porous silicon (PSi) with polydopamine (PDA) could endow the classical drug carrier with a significant photothermal effect for advanced antibacterial therapy and wound disinfection. Specifically, the PSi surface interacts with a Cu2+/PDA complex via a simple and fast surface reduction-induced deposition method, forming the unique CuPDA coated PSi microcarrier (CuPPSi) without blocking the mesoporous structure. The CuPPSi carrier generates a higher near-infrared (NIR) photothermal efficiency and improved drug loading capacity owing to the abundant functional groups of PDA. Stimuli-responsive release of antibacterial Cu2+ and loaded curcumin (Cur) from CuPPSi can be realized under multiple stimuli including pH, reactive oxygen species and NIR laser irradition. Benefited from the carrier's intrinsic multimodal therapy, the CuPPSi-Cur platform exhibits amplified, broad-spectrum, and synergistic antibacterial effect, killing more than 98% for both Staphylococcus aureus and Escherichia coli at a mild PTT temperature (∼45 °C). Notably, the combined therapy promotes migration of fibroblasts with no significant cytotoxicity as revealed through cell experiments in vitro. In bacteria-infected mice model, efficient bacterial ablation and wound healing are further demonstrated with negligible side effects in vivo. Overall, the rational design of a drug carrier with photothermal and therapeutic effects provides a novel intervention for amplifing wound disinfection clinically.

Development and Invitro Evaluation of Solid Lipid Nano Particles Loaded Topical Gel Containing Combination of Drugs Used In The Better Therapy of Psoriasis

The present research work was aimed to develop a Solid lipid nanoparticles (SLNs) based topical gel for the treatment of psoriasis. SLNs were prepared and then incorporated in a topical gel as a carrier. High-Pressure Homogenization method was used to improved drug loading capacity and drug release properties. Excipients like Compritol 888 ATO, Tween 80,Precirol ATO5, Poloxamer407, Cremophor RH40, Carpobol 934, Methyl Paraben, TEA, Distilled water were used. The optimized formulations were based on Zeta potential, analysis of particle size, differential scanning Colorimetery, scanning electron microscopy and study of Invitro drug release. The present research study revealed that the SLNs based Gel containing F4 formulation could potentially exploit as a carrier with improved drug loading capacity and drug release properties. Thus, tacrolimus loaded SLNs formulation can be beneficial in the treatment of psoriasis. It was concluded that the prepared formulation can be used for treatment of psoriasis by using the topical therapy of nanogel and this will attempt to increase the efficacy of the drug at the site of action.

Green synthesis of DOX-loaded hollow MIL-100 (Fe) nanoparticles for anticancer treatment by targeting mitochondria

Fe-based metal-organic frameworks (MOFs) are promising drug delivery materials due to their large surface area, high stability, and biocompatibility. However, their drug loading capacity is constrained by their small pore size, and a further improvement in their drug capacity is needed. In this work, we report an effective and green structural modification strategy to improve drug loading capacity for Fe-based MOFs. Our strategy is to grow MIL-100 (Fe) on carboxylate-terminated polystyrene (PS-COOH) via a sustainable route, which creates a large inner cavity as well as exposure to more functional groups that benefit drug loading capacity. We employ the scanning electron microscope and transmission electron microscope to confirm the hollow structure of MIL-100 (Fe). Up to 30% of drug loading capacity has been demonstrated in our study. We also conduct cell viability tests to investigate its therapeutic effects on breast cancer cells (MDA-MB-231). Confocal laser scanning microscopy imaging confirms cellular uptake and mitochondrial targeting function of doxorubicin-loaded H-M (DOX@H-M) nanoparticles. JC-1 staining of cancer cells reveals a significant change in the mitochondrial membrane potential, indicating the mitochondrial dysfunction and apoptosis of tumor cells. Our study paves the way for the facile synthesis of hollow structural MOFs and demonstrates the potential of applying Fe-based MOFs in breast cancer treatment.

Mission impossible for cellular internalization: When porphyrin alliance with UiO-66-NH2 MOF gives the cell lines a ride

Is it possible to accelerate cell internalization by hybridization of nanomaterials? Herein we support the realization of using metal-organic frameworks (MOFs) with the assistance of rigid porphyrin structure (H2TMP) aimed at drug loading, drug release, relative cell viability, and targeted in vitro drug delivery. There are several MOFs, i.e., UiO-66-NH2 (125 ± 12.5 nm), UiO-66-NH2 @H2TMP (160 ± 14 nm), UiO-66-NH2 @H2TMP@DOX, and UiO-66-NH2 @H2TMP@DOX@RO were synthesized and characterized applying HEK-293, HT-29, MCF-7, and MCF-10A cell lines. MTT investigations proved a significantly higher relative cell viability for H2TMP-aided leaf-extract-coated nanocarriers (above 62 % relative cell viability). Furthermore, the rigid H2TMP structure improved drug loading capacity by 24 % through an enhanced hydrogen bond, van der Waals, and π-π interactions. The in vitro targeted drug delivery experiments were conducted on HT-29 and MCF-7 cell lines. First, nanocarriers were treated with HT-29 cells, where UiO-66-NH2 @H2TMP@DOX@RO appeared as the best nanocarrier. Then, the selected nanocarrier was extracted from the HT-29 cell line and treated with the MCF-7 cell line. For the first time, the DOX remained inside the UiO-66-NH2 @H2TMP@DOX@RO after successful delivery to the HT-29 cell lines was observed on the MCF-7 cell line, and the second targeted drug delivery was performed. The results of this survey can enlighten the future ahead of cell internalization in MOF-based hybrid nanostructures.

Cytochalasin B Treatment and Osmotic Pressure Enhance the Production of Extracellular Vesicles (EVs) with Improved Drug Loading Capacity.

Extracellular vesicles (EVs) have been highlighted as novel drug carriers due to their unique structural properties and intrinsic features, including high stability, biocompatibility, and cell-targeting properties. Although many efforts have been made to harness these features to develop a clinically effective EV-based therapeutic system, the clinical translation of EV-based nano-drugs is hindered by their low yield and loading capacity. Herein, we present an engineering strategy that enables upscaled EV production with increased loading capacity through the secretion of EVs from cells via cytochalasin-B (CB) treatment and reduction of EV intravesicular contents through hypo-osmotic stimulation. CB (10 µg/mL) promotes cells to extrude EVs, producing ~three-fold more particles than through natural EV secretion. When CB is induced in hypotonic conditions (223 mOsm/kg), the produced EVs (hypo-CIMVs) exhibit ~68% less intravesicular protein, giving 3.4-fold enhanced drug loading capacity compared to naturally secreted EVs. By loading doxorubicin (DOX) into hypo-CIMVs, we found that hypo-CIMVs efficiently deliver their drug cargos to their target and induce up to ~1.5-fold more cell death than the free DOX. Thus, our EV engineering offers the potential for leveraging EVs as an effective drug delivery vehicle for cancer treatment.

Facile fabrication of hollow mesoporous bioactive glass spheres: From structural behaviour to in vitro biology evaluation

Bone defects accompanied by infection or inflammation can significantly delay the healing process. To simultaneously achieve controlled release of local antibiotics for infection control and bone healing, bone-implantable delivery systems have been considered as a promising strategy. This study aims to improve drug loading capacity of bone-implantable delivery systems by introducing hollow structure mesoporous bioactive glass nanospheres (HMBGs) through a sol–gel process. Particularly, such core–shell bimodal-porous structured nanoparticles were prepared through a sacrificing template using cetyltrimethylammonium bromide (CTAB) as surfactant. It was found that varying the amount of CTAB during the synthesis process is a simple and effective approach for tuning the particle size, morphology, and structure of HMBGs. For in vitro drug release, HMBGs could sustain storage and release of vancomycin hydrochloride (VAN) via diffusion-controlled mechanism, thereby inhibiting the bacteria growth in the subsequent bacterial study. Moreover, HMBGs incorporated with VAN provided a biomimetic microenvironment favored by cell adhesion and proliferation. These findings support the compatibility of HMBG nanoparticles with antibiotics and their potential application in the treatment of infectious bone defects.

Antibacterial and osteogenic activities of clindamycin-releasing mesoporous silica/carboxymethyl chitosan composite hydrogels.

Conventional treatment of jaw bone infection is often ineffective at controlling bacterial infection and enhancing bone regeneration. Biodegradable composite hydrogels comprised of carboxymethyl chitosan (CMCS) and clindamycin (CDM)-loaded mesoporous silica nanoparticles (MCM-41), possessing dual antibacterial activity and osteogenic potency, were developed in the present study. CDM was successfully loaded into both untreated and plasma-treated MCM-41 nanoparticles, denoted as (p)-MCM-41, followed by the incorporation of each of CDM-loaded (p)-MCM-41 into CMCS. The resulting CDM-loaded composite hydrogels, (p)-MCM-41-CDM-CMCS, demonstrated slow degradation rates (about 70% remaining weight after 14-day immersion), while the CDM-free composite hydrogel entirely disintegrated after 4-day immersion. The plasma treatment was found to improve drug loading capacity and slow down initial drug burst effect. The prolonged releases of CDM from both (p)-MCM-41-CDM-CMCS retained their antibacterial effect against Streptococcus sanguinis for at least 14 days in vitro. In vitro assessment of osteogenic activity showed that the CDM-incorporated composite hydrogel was cytocompatible to human mesenchymal stem cells (hMSCs) and induced hMSC mineralization via p38-dependent upregulated alkaline phosphatase activity. In conclusion, novel (p)-MCM-41-CDM-CMCS hydrogels with combined controlled release of CDM and osteogenic potency were successfully developed for the first time, suggesting their potential clinical benefit for treatment of intraoral bone infection.

Covalent organic framework-engineered polydopamine nanoplatform for multimodal imaging-guided tumor photothermal-chemotherapy.

A covalent organic framework (COF)-engineered polydopamine core-shell nanoplatform (PDA@COF) was developed. The ultrasmall pores and abundant functional sites of the COF endowed the nanoplatform with enhanced drug loading capacity and diminished drug leakage effect. Multimodal imaging-guided photothermal chemo-synergistic tumor-targeted therapy was realized after rational functionalization. This work offers new insights for developing COF-based multifunctional theranostic systems.

Proficiency of nanostructured lipid carriers for the formulation of amphiphilic bile acid oligomers

Biocompatible nanostructured lipid carriers (NLCs) are promising drug delivery vehicles for the formulation of hydrophobic drugs. These nanocarriers comprising liquid lipid inside solid core provide improved drug loading capacity compared to other existing lipid-based nanocarriers such as solid lipid nanoparticles or liquid emulsions. In the present report, we successfully employed D12DAB based NLCs for the formulation of bile acid-derived amphipathic oligomers. The prepared nano-formulation rendered adequate aqueous solubility to these bioactive bile acid oligomers. Hydrodynamic diameter, viscosity, surface tension, conductivity and zeta potential of the prepared NLCs were determined by dynamic light scattering, viscometer, tensiometer, conductivity meter, and zeta analyzer and was found to be in the range of 122−147 nm, 2.07–2.15 mPa.s, 29.7–30.2 mN/m, 540−550 mS/m, and 15.7−16 mV, respectively. In addition, Field Emission Scanning Electron Microscopy and Transmission Electron Microscopy analysis were performed to understand the external morphology and internal structure of synthesized NLCs. The applications of the synthesized NLCs to encapsulate dapsone and its release kinetics were studied in detail. The results conferred the formation of bile acid-enriched stable NLCs which could be a promising system to formulate and/or deliver several combinations of antibiotics or other bioactive agents to treat undesired physiological conditions.

Hyaluronic Acid Scaffolds and Injectable Gels for Healing of Induced Arthritis in Rat Knee: Effect of Prednisolone Revisited

Considering the absence of a definite cure for osteoarthritis and problems of existing approaches, designing scaffolds for cartilage regeneration by tissue engineering methods seems necessary. Optimization of scaffolds properties is one of the biggest challenges in this area. Due to contradicting reports regarding efficacy and safety of intra-articular injections of corticosteroids, further evaluation of these agents by their incorporation into a designed scaffold could be beneficial. On this basis, a hyaluronic acid (HA) scaffold was designed in two forms: shear-thinning injectable gel and lyophilized implantable disk. Polyethylene glycol diglycidyl ether (PEGDGE) was used as cross-linker. After optimization of scaffolds properties, in vivo efficacy of the most optimum formulation (HA 2%, PEGDGE 0.5%) in the presence and absence of prednisolone (0.1% W/V) was evaluated. In vivo studies in rats showed that after 10 weeks, HA scaffolds, in both forms, repaired damaged articular cartilage to some extent but incorporation of prednisolone into the scaffold showed no additional benefit. Overall it seems that implantable scaffolds of HA could be a potential therapeutic choice for cartilage regeneration and corticosteroids in long term may also reverse these beneficial effects. Hyaluronic acid (HA) is one of the major components of the extracellular matrix and cartilage tissue. There are numerous reports on the efficacy of different scaffolds of HA for cartilage regeneration. New engineering methods focus on retaining the scaffolds in the site for long time as well as loading therapeutic agents to accelerate the healing process. In situ injection of corticosteroids is one of the routine interventions for osteoarthritis. Here, the effect of loading prednisolone as an anti-inflammatory agent into the shear thinning gels and implantable disks of HA for treatment of an induced arthritis in rat knee was revisited. In future studies we will upgrade the scaffold by mixing HA with some other biopolymers to increase the strength and retention of the system and to improve drug loading capacity. It seems that loading specific growth factors would be an alternative to corticosteroids with higher efficacy and lower side effects.

A Novel Technique to Improve Drug Loading Capacity of Fast/Extended Release Orally Dissolving Films with Potential for Paediatric and Geriatric Drug Delivery.

Orally dissolving films (ODFs) have received much attention as potential oral drug delivery systems for paediatric and geriatric patients, particularly those suffering from dysphagia. With their unique properties and advantages, the technology offers improved patient compliance and wider acceptability, eliminates the fear of choking, enables ease of administration and offers dosing convenience, without the requirement of water. However, adequate drug loading remains a challenge. The aim of this study was to mechanistically design and evaluate fast and extended release ODF formulations with high drug loading capacity, displaying good physicochemical and mechanical properties, as a potential dosage form for paediatric and geriatric use employing a slightly soluble model drug-ibuprofen. Different polymers (0.6-10% HPMC, 0.6-1.5% guar gum), plasticisers (0.1-0.5% glycerine, 0.1% sorbitol) and processing conditions (40-60°C drying temperatures, 8-16h drying times) were investigated to produce films using the solvent casting method. Molecular compatibility was assessed using TGA, XRD and FTIR whereas film topography was assessed using SEM. Maximum ibuprofen load in single films was 20.7mg/film (54.4%) and released 100% drug content in 5min, while triple layered ibuprofen-loaded films contained 62.2mg/film and released 100% drug release in 1h. The ODFs demonstrated good disintegration time using low volume artificial saliva media and high dosage from uniformity. This study provides a mechanistic insight to the design and evaluation of fast and extended release ODFs with high drug loading, suitable for administration to paediatric and geriatricpatients.

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review.

The efficacy of current standard chemotherapy is suboptimal due to the poor solubility and short half-lives of chemotherapeutic agents, as well as their high toxicity and lack of specificity which may result in severe side effects, noncompliance and patient inconvenience. The application of nanotechnology has revolutionized the pharmaceutical industry and attracted increasing attention as a significant means for optimizing the delivery of chemotherapeutic agents and enhancing their efficiency and safety profiles. Nanostructured lipid carriers (NLCs) are lipid-based formulations that have been broadly studied as drug delivery systems. They have a solid matrix at room temperature and are considered superior to many other traditional lipid-based nanocarriers such as nanoemulsions, liposomes and solid lipid nanoparticles (SLNs) due to their enhanced physical stability, improved drug loading capacity, and biocompatibility. This review focuses on the latest advances in the use of NLCs as drug delivery systems and their preparation and characterization techniques with special emphasis on their applications as delivery systems for chemotherapeutic agents and different strategies for their use in tumor targeting.