Alendronate Research Articles

Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs) are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery of BPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolving and hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawley rats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkaline phosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls. Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVX controls and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. In the distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21 % in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. This proof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternative for weekly osteoporosis management.

Airway consequences of alendronic acid aspiration.

Bisphosphonates are commonly prescribed medications to prevent and treat osteoporosis. Although possessing low side effect profiles, the potential for severe topical effects is rare but important. Irritation of the upper gastrointestinal tract is well documented; however, the risk and effects of accidental aspiration are rarely reported.Attention is drawn to a case recently managed at a tertiary head and neck centre where a patient in their 70s was admitted in respiratory distress 3 days after aspirating alendronic acid. This case highlights the potential risk of topical chemical injury posed to the airway by bisphosphonates.Bisphosphonates should be prescribed with detailed and specific counselling regarding this risk. Pharmacological product literature should be updated to reflect the risk. Clinical teams should be aware of and vigilant for the delayed presentation and prolonged symptom course of such injuries. Prompt airway intervention and techniques to minimise further mucosal trauma ensure optimal outcomes.

Predictors of discontinuation of osteoporosis treatment: sub-analysis of the Japanese osteoporosis intervention trial-05 (JOINT-05).

To identify predictors of discontinuing treatment with teriparatide (TPTD) and alendronate (ALN), data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high risk of fracture were re-analyzed. Participants received sequential therapy with once-weekly TPTD for 72weeks followed by ALN for 48weeks (TPTD-ALN group) or monotherapy with ALN for 120weeks (ALN group). Background data including comorbidities, fracture prevalence, cognitive function, quality of life, activities of daily living, bone metabolism parameters, and nutrient intake were collected. The endpoints were 3 types of discontinuations by the reason: a poor compliance, adverse events (AEs), or any reason including those unrelated to AEs or poor compliance. Odds ratios (ORs) of baseline predictors of discontinuation were evaluated by single or multiple regression analysis. A total of 234 (49.0%) patients in the TPTD-ALN group and 167 (34.2%) patients in the ALN group discontinued. In the TPTD-ALN group, a lower serum calcium level was a significant predictor of compliance-related discontinuation. Serum 25-hydroxyvitamin D levels were lower in patients with lower serum calcium levels than with higher serum calcium levels. In the ALN group, poor cognitive function was significantly associated with compliance-related discontinuation, and higher body mass index and alcohol intake were predictors of AE-related discontinuation. Predictors of discontinuation were drug-specific. Lower serum calcium levels and poor cognitive function were predictors of discontinuing once-weekly TPTD and ALN, respectively. When starting TPTD and ALN treatment, careful attention to patients with lower serum calcium levels and poor cognitive function, respectively, may be needed for better treatment continuity.

Controlled release in sodium alendronate/halloysite/hydroxyapatite/gelatin nanocomposite scaffolds: A new insight into bone tissue engineering

The use of smart scaffolds with drug release capabilities is now widely recognized as a key approach in designing hard tissue substitutes. In this study, alendronate sodium (AL) was bound to halloysite nanotube (HNT) sheets through ionic and π-π interactions. Hydroxyapatite (HA) powder was synthesized using the co-precipitation method, and the drug/carrier complex was subsequently incorporated into a hydroxyapatite/gelatin (GEL) matrix. Composite scaffolds of GEL/HA/HNT/AL were then created using a freeze-drying technique. Different concentrations of HNT (0.5 %, 1 %, and 2 %) were tested to determine the optimal formulation. The scaffolds were subjected to extensive physical, chemical, and mechanical evaluations using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), compressive stress tests, and measurements of density and porosity. The release profile of alendronate sodium, scaffold swelling behavior in water, bioactivity, and in vitro performance were thoroughly assessed. Cell viability was tested using the MTT assay, while alkaline phosphatase (ALP) activity and cell adhesion studies were performed to evaluate osteogenic potential. The results revealed that the GEL/HA/1 % HNT/AL nanocomposite scaffold exhibited excellent properties, including efficient drug release, optimal swelling rates, and enhanced bioactivity. The MTT assay confirmed high cell viability, and both ALP activity and cell adhesion studies indicated strong potential for bone cell differentiation and repair. Thus, the GEL/HA/1 % HNT/AL nanocomposite scaffold is a highly promising platform for bone tissue engineering.

Defect-Engineered Metal-Organic Frameworks as Nanocarriers for Pharmacotherapy: Insights into Intracellular Dynamics at The Single Particle Level.

Nanoscale Metal-Organic Frameworks (nanoMOFs) are widely implemented in a host of assays involving drug delivery, biosensing catalysis, and bioimaging. However, the cell pathways and cell fate remain poorly understood. Here, a new fluorescent nanoMOF integrating ATTO 655 into surface defects of colloidal UiO-66 is synthesized, allowing to track the spatiotemporal localization of Single nanoMOF in live cells. Density functional theory reveals the stronger binding of ATTO 655 to the Zr6 cluster nodes compared with phosphate and Alendronate Sodium. Parallelized tracking of the spatiotemporal localization of thousands of nanoMOFs and analysis using machine learning platforms reveals whether nanoMOFs remain outside as well as their cellular internalization pathways. To quantitatively assess their colocalization with endo/lysosomal compartments, a colocalization proxy approach relying on the nanoMOF detection of particles in one channel to the signal in the corresponding endo/lysosomal compartments channel, considering signal versus local background intensity ratio and signal-to-noise ratio is developed. This strategy mitigates colocalization value inflation from high or low signal expression in endo/lysosomal compartments. The results accurately measure the nanoMOFs' colocalization from early to late endosomes and lysosomes and emphasize the importance of understanding their intracellular dynamics based on single-particle tracking for optimal and safe drug delivery.

The hyaluronic acid-gelatin hierarchical hydrogel for osteoporotic bone defect repairment

Osteoporotic bone defects are serious medical problems due to their sparse bone structure, difficulty in restoration and reconstruction, and high recurrence rates, which also result in heavy economic and social burdens. Herein, we developed a hierarchical hydrogel composed of alendronate sodium (AS)/Mg2+-loaded inverse opal methylpropenylated gelatin (GelMA) hydrogel microspheres (IOHM-AS-Mgs) within methylpropenylated poly(hyaluronic acid) (HAMA) for osteoporotic bone defect treatment. The IOHM-AS-Mgs displayed good cytocompatibility and cell adhesion and strongly stimulated osteogenesis at the transcriptomic and protein levels. When this treatment was applied to the osteoporotic bone defect area, HAMA was used to fix the microspheres. The results of the microcomputed tomography (micro-CT) and histological analyses indicated that the hierarchical hydrogel had the best therapeutic effect. Therefore, this hydrogel is a new candidate for osteoporotic bone defect treatment.

Study on the Condensation of 2-((4-Aminophenyl)sulfonyl)ethyl Hydrogen Sulfate with Alendronic Acid: Mechanism, Kinetics, and Reactor Modeling

Study on the Condensation of 2-((4-Aminophenyl)sulfonyl)ethyl Hydrogen Sulfate with Alendronic Acid: Mechanism, Kinetics, and Reactor Modeling

Alendronic acid

Alendronic acid

Onion (Allium cepa L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells.

Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis.

Construction of Tough Hydrogel Cross-Linked via Ionic Interaction by Protection Effect of Hydrophobic Domains.

Most hydrogels have poor mechanical properties, severely limiting their potential applications, and numerous approaches have been introduced to fabricate more robust and durable examples. However, these systems consist of nonbiodegradable polymers which limit their application in tissue engineering. Herein, we focus on the fabrication and investigate the influence of hydrophobic segments on ionic cross-linking properties for the construction of a tough, biodegradable hydrogel. A biodegradable, poly(γ-glutamic acid) polymer conjugated with a hydrophobic amino acid, l-phenylalanine ethyl ester (Phe), together with an ionic cross-linking group, alendronic acid (Aln) resulting in γ-PGA-Aln-Phe, was initially synthesized. Rheological assessments through time sweep oscillation testing revealed that the presence of hydrophobic domains accelerated gelation. Comparing gels with and without hydrophobic domains, the compressive strength of γ-PGA-Aln-Phe was found to be six times higher and exhibited longer stability properties in ethylenediaminetetraacetic acid solution, lasting for up to a month. Significantly, the contribution of the hydrophobic domains to the mechanical strength and stability of ionic cross-linking properties of the gel was found to be the dominant factor for the fabrication of a tough hydrogel. As a result, this study provides a new strategy for mechanical enhancement and preserves ionic cross-linked sites by the addition of hydrophobic domains. The development of tough, biodegradable hydrogels reported herein will open up new possibilities for applications in the field of biomaterials.

Poloxamer 407 modified collagen/β-tricalcium phosphate scaffold for localized delivery of alendronate.

Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/β-tricalcium phosphate (β-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications.

A hydrogel containing Mg2+ with improved osteogenesis, enhanced endochondral ossification, and modulated inflammation for bone-repair applications

In this study, an injectable, porous, and Mg2+-loaded hydrogel with the ability to scavenge local reactive oxygen species was developed for bone-repair applications. Alendronate sodium with a specific binding affinity to Mg2+ was incorporated into the hydrogel through a Schiff’s base reaction with oxidized dextran. The porous hydrogel, which was cross-linked by catechol-modified chitosan to maintain its mechanical properties, showed enhanced cell viability, proliferation, differentiation of human bone marrow stromal cells in vitro, and osteogenic property in a rat-femur defect model. The hydrogel promoted the regeneration of bone tissue including ossification and particularly endochondral ossification, indicating a progressive healing process. The formed bone tissue exhibited a dense and layered structure, substantiating its effectiveness in osteogenic differentiation. The hydrogel also affected the polarization of macrophages and inhibited the M1 phenotype associated with tissue repair and regeneration, exhibiting the potential to reduce local inflammatory response and benefit bone repair. Overall, the hydrogel can be anticipated as a promising biomaterial for bone repair because of its multiple biofunctions including enhanced osteogenesis and endochondral ossification, and modulation of inflammation.

Fluffy hybrid nanoadjuvants for reversing the imbalance of osteoclastic and osteogenic niches in osteoporosis

Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivo results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.

Evaluating the impact of COVID-19 on DXA waiting lists and osteoporosis prescription trends in England 2019-2023.

This study investigates the impact of COVID-19 on DXA scan waiting lists, service recovery and osteoporosis medication prescriptions in the NHS following the March 2020 national lockdowns and staff redeployment. Data from March 2019 to June 2023, including NHS digital diagnostics waiting times (DM01) and osteoporosis medication prescriptions from the English Prescribing Dataset (EPD), were analysed. This encompassed total waiting list data across England's seven regions and prescribing patterns for various osteoporosis medications. Analyses included total activity figures and regression analysis to estimate expected activity without COVID-19, using R for all data analysis. In England, DXA waiting lists have grown significantly, with the yearly mean waiting list length increasing from 31,851 in 2019 to 65,757 in 2023. The percentage of patients waiting over 6 weeks for DXA scans rose from 0.9% in 2019 to 40% in 2020, and those waiting over 13 weeks increased from 0.1% in 2019 to 16.7% in 2020. Prescription trends varied, with increases in denosumab, ibandronic acid and risedronate sodium and decreases in alendronic acid, raloxifene hydrochloride and teriparatide. A notable overall prescription decrease occurred in the second quarter of 2020. COVID-19 has significantly increased DXA scan waiting lists with ongoing recovery challenges. There is a noticeable disparity in DXA service access across England. Osteoporosis care, indicated by medication prescriptions, also declined during the pandemic. Addressing these issues requires focused investment and effort to improve DXA scan waiting times and overall access to osteoporosis care in England.

Injectable and high-strength PLGA/CPC loaded ALN/MgO bone cement for bone regeneration by facilitating osteogenesis and inhibiting osteoclastogenesis in osteoporotic bone defects

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to the imbalance between osteogenesis and osteoclastogenesis, making osteoporotic bone defects healing a significant clinical challenge. Calcium phosphate cement (CPC) is a promising bone substitute material due to its good osteoinductive activity, however, the drawbacks such as fragility, slow degradation rate and incapability to control bone loss restrict its application in osteoporotic bone defects treatment. Currently, we developed the PLGA electrospun nanofiber sheets to carry alendronate (ALN) and magnesium oxide nanoparticle (nMgO) into CPC, therefore, to obtain a high-strength bone cement (C/AM-PL/C). The C/AM-PL/C bone cement had high mechanical strength, anti-washout ability, good injection performance and drug sustained release capacity. More importantly, the C/AM-PL/C cement promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and neovascularization via the release of Mg2+ (from nMgO) and Ca2+ (during the degradation of CPC), and inhibited osteoclastogenesis via the release of ALN in vitro. Moreover, the injection of C/AM-PL/C cement significantly improved bone healing in an OP model with femur condyle defects in vivo. Altogether, the injectable C/AM-PL/C cement could facilitate osteoporotic bone regeneration, demonstrating its capacity as a promising candidate for treatment of osteoporotic bone defects.

#1273 Rapidly progressive glomerulonephritis with anti-neutrophil cytoplasmic antibodies, in a patient on golimumab

Abstract Background 73-year-old Chinese lady presented with fever, gross hematuria, and dysuria of 1-week duration. She has seronegative arthritis and was treated with human anti-tumor necrosis factor alpha monoclonal antibody (TNF-alpha inhibitor), golimumab injection 50 mg monthly, as she had previous adverse reaction with sulfasalazine and methotrexate. She suffered from severe osteoporosis and was treated with oral alendronic acid. At presentation, her blood pressure was 172/76 mmHg and pulse rate 100 beats per minute. The highest recorded temperature was 38.1 degrees Celsius. Clinical examination was unremarkable. She was diagnosed with rapidly progressive glomerulonephritis (RPGN). Creatinine at presentation was 252 µmol/L, estimated glomerular filtration rate (eGFR) 16 mL/min/1.73 m2. Two months ago, her creatinine was 68 µmol/L, eGFR 66 mL/min/1.73 m2. Urinalysis showed dysmorphic red blood cells of more than 2250 per high power field, few white blood cells, and no epithelial cells. Urine protein/creatine ratio (UPCR) was 2.3 g/g and serum albumin level was 30 g/L. ANA was borderline raised at 1:160 titer with homogeneous pattern. Anti-double stranded DNA (anti-dsDNA) was indeterminate at 29.34 IU. Anti-myeloperoxidase (MPO) antibody was positive at 162 RU/mL (Normal < 20 RU/mL). Anti-proteinase-3 (PR3) antibody was negative. Serum complement levels (C3 and C4) were normal. Screening for hepatitis B, hepatitis C, and HIV was negative. Ultrasound imaging of the kidneys showed raised renal echoes and resistive index. Percutaneous kidney biopsy was performed. On light microscopy, 19 glomeruli were seen. Some displayed segmental increase in mesangial cells and expansion of mesangial matrix. 4 glomeruli showed cellular crescents (Fig. 1). Immunofluorescence showed dominant 2+ staining for Immunoglobulin A (IgA) in the mesangium and electron microscopy revealed electron dense deposits in the mesangial and para-mesangial region. An occasional tubuloreticular structure was found. Diagnosis of IgA nephropathy was made and Oxford classification was M0 E1 S0 T0 C1. Results Our patient presented with rapidly progressive glomerulonephritis (RPGN) with positive MPO antibody, as well as ANA and anti-dsDNA at indeterminate levels. TNF-alpha inhibitors may lead to autoantibody formation and kidney biopsy was the key in clinching the diagnosis for our patient. Diagnosis of IgA nephropathy was made on the basis of dominant mesangial IgA on immunofluorescence and ultrastructural electron dense deposits within the mesangial and para-mesangial area. To our best knowledge, there has been only one case of IgA nephropathy reported with golimumab that occurred after 3 years and with mild albuminuria and no decline in renal function. Golimumab was promptly discontinued for our patient and she was inducted with pulsed methylprednisolone and high dose oral prednisolone 1 mg/kg/day. As she had history of severe osteoporosis, oral mycophenolate mofetil at 750 mg twice a day was commenced as steroid sparing agent. Prednisolone dose was then tapered to 0.5 mg/kg/day. She achieved full clinical remission after 3 months of immunosuppressive therapy. MPO antibody level decreased to normal after 5 months. Arthritis activity remained quiescent and she was maintained on low dose prednisolone. Conclusion We report a case of IgA nephropathy with crescents associated with golimumab. Treatment was successful with withdrawal of drug, oral prednisolone and mycophenolate mofetil.

Farnesyl Diphosphate Synthase Gene Associated with Loss of Bone Mass Density and Alendronate Treatment Failure in Patients with Primary Osteoporosis.

Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the FDPS gene, is associated with reduced gene transcription. This study evaluates the FDPS variant rs2297480 (A > C) association with OP patients' response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) (n = 20) and non-responders (OP-NR) (n = 40). We observed an association of CC genotype with treatment failure (p = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = -2.21% ± 2.56; p = 0.026) and TH (CC = -2.06% ± 1.84; p = 0.015) after two years of alendronate sodium treatment. Relative expression of the FDPS gene was also evaluated in OP-R and OP-NR patients. Higher expression of the FDPS gene was also observed in OP-NR group (FC = 1.84 ± 0.77; p = 0.006) when compared to OP-R. In conclusion, the influence observed of FDPS expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis.

Alendronate carbon dots targeting bone immune microenvironment for the treatment of osteoporosis

Bisphosphonates (BPs) are some of the most widely used drugs in osteoporosis (OP) treatment, but they can cause severe side effects such as bisphosphonate-related osteonecrosis of the jaw (BRONJ), causing great pain in patients. It is necessary to develop a novel drug for treating OP with fewer side effects. In this study, novel carbon dots, ALEN-CDs, derived from polyethylene glycol (PEG) and alendronate (ALEN) are developed. ALEN-CDs have good biocompatibility, photoluminescence (PL) properties, and bone-targeting ability. They can inhibit the differentiation and maturation of osteoclasts, play an immunoregulatory role by inhibiting macrophage polarization to the pro-inflammatory M1 phenotype, and promote polarization to the anti-inflammatory M2 phenotype. It is worth noting that compared with ALEN, high-dose applications of ALEN-CDs do not lead to BRONJ, which may be related to the regulatory effect on M2 macrophage polarization. Moreover, in vivo studies show that ALEN-CDs significantly reduce bone loss and improve OP in ovariectomized mice (OVX). And a proteomic analysis suggestes that ALEN-CDs regulate the bone immune microenvironment by affecting mitochondrial metabolism, especially oxidative phosphorylation (OXPHOS). In conclusion, ALEN-CDs could directly inhibit osteoclast differentiation and regulate the bone immune microenvironment and may be a promising drug for OP treatment.

Luminescent Alendronic Acid-Conjugated Micellar Nanostructures for Potential Application in the Bone-Targeted Delivery of Cholecalciferol

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV–visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.

Fabrication and evaluation of dual-function nanofiber membrane for guided periodontal tissue and bone regeneration with controlled release of alendronate sodium

Bone defect is one of the most common complications arising from more severe forms of periodontitis and occurring mainly because of the accumulation of osteoclasts at the inflamed site. Bisphosphonates inhibit this process by promoting apoptosis of the osteoclasts. The present study aimed to fabricate nanofibrous membranes for both guided periodontal regeneration and controlled release of alendronate sodium (ALN) in the management of periodontitis. The membranes were developed by electrospinning polyvinyl alcohol, polycaprolactone, or a blend of them. Then, they were evaluated for in vivo performance and biocompatibility by an alternative method in rats. Uniform and randomly aligned nanofibers with a mean diameter lower than 600 nm were successfully obtained by electrospinning. The formulation indicated suitable mechanical strength and elasticity. A controlled in vitro release profile over 168 h was observed for each formulation, and the optimized one showed acceptable cell toxicity to be considered non-cytotoxic. The in vivo evaluation showed a sustained release of ALN during 28 days to the surrounding tissues without causing any irritation or damage. The ALN-loaded nanofibrous membrane showed suitable characteristics to be used as a dual-function periodontal membrane with space-maintaining properties and modified release of ALN for promoting bone regeneration during the recovery process.