Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis.

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (- 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.

Emerging Advances in Nanocarriers Approaches in the Effective Therapy of Pain Related Disorders: Recent Evidence and Futuristic Needs.

Pain disorders are the primary cause of disability nowadays. These disorders, such as rheumatoid arthritis (RA) and osteoarthritis (OA), cause loss of function, joint pain and inflammation and deteriorate the quality of life. The treatment of these inflammatory diseases includes anti-inflammatory drugs administered via intra-articular, topical or oral routes, physical rehabilitation or surgery. Owing to the various side effects these drugs could offer, the novel approaches and nanomaterials have shown potential to manage inflammatory diseases, prolonged half-life of anti-inflammatory drugs, reduced systemic toxicity, provide specific targeting, and refined their bioavailability. This review discusses in brief about the pain pathophysiology and its types. The review summarizes the conventional therapies used to treat pain disorders and the need for novel strategies to overcome the adverse effects of conventional therapies. The review describes the recent advancements in nanotherapeutics for inflammatory diseases using several lipids, polymers and other materials and their excellent efficiency in improving the treatment over conventional therapies. The results of the nanotherapeutic studies inferred that the necessity to use nanocarriers is due to their controlled release, targeting drug delivery to inflamed tissues, low toxicity and biocompatibility. Therefore, it is possible to assert that nanotechnology will emerge as a great tool for advancing the treatment of pain disorders in the near future.

Efficacy and Safety of Pregabalin Prolonged Release-Etoricoxib Combination Compared to Etoricoxib for Chronic Low Back Pain: Phase 3, Randomized Study.

INTRODUCTION: Currently available treatments for chronic lower back pain (CLBP) do not adequately address both nociceptive and neuropathic components of pain. We evaluated efficacy and safety of fixed-dose combination (FDC) of low-dose pregabalin prolonged release 75 mg-etoricoxib 60 mg to address both pain components. METHODS: This randomized phase 3 trial conducted at 12 centres across India evaluated efficacy (based on mean change in numeric rating scale [NRS], Roland-Morris disability questionnaire [RDQ], visual analogue scale [VAS], patient global impression of improvement [PGI-I], clinical global impression of improvement [CGI-I] and rescue medication consumption) and safety of FDC in comparison to etoricoxib alone in adult patients with CLBP. Treatment duration was 8 weeks. RESULTS: Of the 371 patients screened, 319 were randomized and considered for efficacy and safety analysis. Both treatment groups had no significant difference in terms of demography and baseline disease characteristics. Significantly better outcomes with FDC compared to etoricoxib were observed at week 4 onwards. At week 8, both groups showed significant reduction in mean NRS score from baseline (- 4.00 ± 1.65 in FDC; - 2.92 ± 1.59 in etoricoxib) with mean NRS score being significantly less in the FDC group compared to etoricoxib group (3.26 ± 1.56 vs 4.31 ± 1.56; p < 0.0001). The FDC was more effective than etoricoxib in terms of significantly greater reduction in RDQ score (- 9.28 ± 4.48 vs - 6.78 ± 4.34; p < 0.0001) and VAS score (- 37.66 ± 18.7 vs - 28.50 ± 16.31; p < 0.0001) at week 8. The FDC was also better in terms of significantly more patients reporting their condition as 'very much better' (36.9% vs 5.0%; p < 0.0001) and clinicians reporting patient's condition as 'very much improved' (36.3% vs 5.7%; p < 0.0001). Overall, study medications were well tolerated. CONCLUSION: FDC of pregabalin and etoricoxib provided significant benefits in reducing pain and improving functional status compared with etoricoxib alone in patients with CLBP. Pregabalin prolonged release-etoricoxib FDC could be one of the treatment options for early and sustained pain relief and improvement in quality-of-life in treating CLBP as it addresses both neuropathic and nociceptive components of pain. TRIAL REGISTRATION: CTRI/2018/10/015886.

Low back pain is one of the most common causes of loss of productivity worldwide. About 60% of Indians suffer from low back pain at some point. Low back pain that persists for more than 3 months is classified as chronic low back pain which mostly includes both nociceptive and neuropathic components. Monotherapies, if prescribed, are not completely effective, as they generally only target either nociceptive or neuropathic components of pain. Multiple drugs are usually needed at multiple times a day, at higher doses for optimal effectiveness, and in most cases they have significant side effects if taken over prolonged periods and also add to the pill burden. To minimize treatment-associated adverse effects, and to increase treatment compliance, while addressing both the components of pain, we developed a fixed-dose combination of low-dose pregabalin prolonged release and etoricoxib. A phase 3 trial was designed to assess the efficacy and safety of the fixed-dose combination in comparison with etoricoxib alone in treating chronic low back pain. The combination demonstrated statistically and clinically significant improvement in patient-reported outcomes­pain, functionality and quality of life­as early as 4 weeks after starting the medication. No severe or serious adverse effects were reported. Thus, the combination of low-dose pregabalin prolonged release and etoricoxib could provide an option for optimal management of chronic low back pain. This would provide multiple benefits, such as addressing both nociceptive and neuropathic components of chronic low back pain, reducing drug-related adverse effects because of low dose, reducing pill burden and thereby increasing drug compliance.

Is modified reverse step-cut osteotomy better than Yun's reverse V osteotomy in paediatric cubitus varus deformity correction? A prospective, double-blinded, randomized controlled trial.

BACKGROUND: Various corrective osteotomy techniques have been described in the literature for correcting paediatric cubitus varus. But we are still in search of the perfect technique that gives maximum possible deformity correction and cosmetic appearance that satisfies parents with minimal complications. We compared the outcomes of two technically sound osteotomy techniques having minimal postoperative lateral condyle prominence described in the literature. RESEARCH QUESTION: Is modified reverse step-cut osteotomy (MRSO) better in terms of clinical, radiological, and cosmetic outcomes than Yun's reverse V osteotomy (RVO) in pediatric cubitus varus deformity correction? METHODS: In total, 20 children with unilateral cubitus varus resulting from malunited supracondylar humerus fractures were included. Randomization was done by computer-generated random slips. A total of ten cases each were operated by MRSO and RVO techniques, respectively. Clinical, radiological, and cosmetic appearance assessments were done at the final two year follow-up and compared between the two groups. RESULTS: The mean age of children in the MRSO and RVO groups is 9.9 years (3-16) and 8.6 years (3-16), respectively. The mean pre-operative carrying angle in the deformed elbow of MRSO and RVO group was - 20.5° and - 19.5°, respectively, and the mean pos-toperative carrying angle in the corrected elbow of MRSO and RVO group was + 6.8° and + 6.5°, respectively. Regarding the lateral prominence index (LPI), a positive correlation was noted between pre-operative and post-operative periods with a value of 0.855 and 0.844 (p value: 0.001 and 0.03, respectively) in both MRSO and RVO groups, respectively. However, the change was statistically not significant when compared between the two groups (p = 0.63). There was no statistically significant difference (p > 0.05) when the clinical, radiological, and cosmetic outcomes were compared between the groups at final follow-up. CONCLUSION: The surgeon can choose either one of these techniques based on their expertise since the results of both the techniques are comparable in terms of clinical, radiological, and cosmetic outcomes.

Effects of type 2 diabetes on the viscoelastic behavior of human trabecular bone.

Type 2 diabetes (T2D) is a well-known disease that impaired bone mechanical properties and increases the risk of fragility fracture. The bone tissue is a viscoelastic material that means the loading rate determines its mechanical properties. This study investigates the impact of T2D on the viscoelastic properties of human bone and its association with microstructure and biochemical properties. INTRODUCTION: Viscoelasticity is an important mechanical property of bone and for this the interaction of individual constituents of bone plays an important role. The viscoelastic nature of bone can be affected by aging and diseases, which can further influence its deformation and damage behavior. METHODS: The present study investigated the effects of T2D on the viscoelastic behavior of trabecular bone. The femoral heads of T2D (n = 26) and non-T2D (n = 40) individuals with hip fragility fractures were collected for this investigation. Following the micro-CT scanning of all bone samples, the stress relaxation and dynamic mechanical analysis (DMA) tests were performed to quantify the viscoelasticity of bone. Further, a correlation analysis was performed to investigate the effects of alteration in bone microstructural and biochemical parameters on viscoelasticity. RESULTS: The stress relaxation and frequency sweep responses of T2D and non-T2D trabecular bone specimens were not found significantly different. However, the storage modulus, initial stiffness, and initial stress were found lower in T2D bone. The significant correlation of percentage stress relaxed is obtained between the mineral content (r= - 0.52, p-value = 0.003), organic content (r = 0.40, p-value = 0.02), and mineral-to-matrix ratio (r = - 0.43, p-value = 0.009). Further, storage and loss modulus were correlated with bone volume fraction (BV/TV) for both groups. The stress relaxation and frequency sweep characteristics were not found significantly connected with the other chemical, structural, or clinical parameters. CONCLUSION: This study suggests that T2D does not affect the time-dependent response of human femoral trabecular bone. The viscoelastic properties are positively correlated with organic content and negatively correlated with mineral content.

A Prospective Study Evaluating Factors Affecting Functional Outcome in Patients with Floating Elbow Injury.

BACKGROUND: Floating elbow injuries are complex injuries. Due to frequent association with severe soft tissue injuries and polytrauma, they have unpredictable functional outcome. This prospective study is aimed to evaluate the factors affecting functional outcome. METHODS: Thirty patients with floating elbow injuries were treated at a level 1 trauma center from July 2018 to June 2019 with minimum follow-up of 9 months. The outcome was assessed by disability for arm shoulder and hand score (DASH) and mayo elbow performance score (MEPS). RESULTS: The overall incidence was 16.09 per 1000, mostly caused by road traffic accidents and all cases were managed surgically. Age, gender, education, occupation, arm dominance, and mechanism of injury did not significantly affect the outcomes. Open fractures and patients requiring staged procedure were associated with poorer outcomes (p < 0.05); however, delay in surgery for more than 24 h significantly increased the rate of complications. There was no statistical difference in the proportion of patients who had nerve injury pre operatively and post operatively on the final outcome. CONCLUSION: Floating elbow injuries are relatively rare but nowadays the numbers are on the rise. Timely intervention with a multimodal approach and well-supervised rehabilitation can assure better final outcome.

Can fingernail quality predict bone damage in Type 2 diabetes mellitus? a pilot study.

Type 2 diabetes mellitus (T2DM) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, including bone. It is well known that the clinical utility of areal bone mineral density (aBMD) is limited to assess bone strength in individuals with T2DM. Therefore, there is a need to explore new diagnostic techniques that can better assist and improve the accuracy of assessment of bone tissue quality. The present study investigated the link between bone and fingernail material/compositional properties in type 2 diabetes mellitus (T2DM). For that, femoral head and fingernail samples were obtained from twenty-five adult female patients (with/without T2DM) with fragility femoral neck fractures undergoing hemi/total hip arthroplasty. Cylindrical cores of trabecular bone were subjected to micro-CT, and lower bone volume fraction was observed in the diabetic group than the non-diabetic group due to fewer and thinner trabeculae in individuals with T2DM. The material and compositional properties of bone/fingernail were estimated using nanoindentation and Fourier Transform Infrared Spectroscopy, respectively. Both bone/fingernails in T2DM had lower reduced modulus (Er), hardness (H), lower Amide I and Amide II area ratio (protein content), higher sugar-to-matrix ratio, and relatively high carboxymethyl-lysine (CML) content compared with non-diabetic patients. Sugar-to-matrix ratio and relative CML content were strongly and positively correlated with HbA1c for both bone/fingernail. There was a positive correlation between bone and fingernail glycation content. Our findings provide evidence that the degradation pattern of bone and fingernail properties go hand-in-hand in individuals with T2DM. Hence, the fingernail compositional/material properties might serve as a non-invasive surrogate marker of bone quality in T2DM; however, further large-scale studies need to be undertaken.

Effect of ageing on microstructure and fracture behavior of cortical bone as determined by experiment and Extended Finite Element Method (XFEM).

Bone fracture is a severe health concern; therefore, understanding the causes of bone fracture are crucial. This paper investigates the microstructure and fracture behaviour of cadaveric cortical bone of two different groups (Young, n= 6; Aged, n=7). The microstructure is obtained from µ-CT images, and the material parameters are measured with nanoindentation. Fracture behaviour in transverse and longitudinal orientations is investigated experimentally and numerically. The results show that the Haversian canal (HC) size increases and the osteon wall thickness (OWT) decreases significantly in the aged group, whereas a nonsignificant difference is found in tissue properties. The crack initiation (Jic) and crack growth (Jgrow) toughness of the aged group are found to be significantly lower (p<0.01) than the young group in the transverse orientation; however, for the longitudinal orientation, only the value of Jic in the aged group is found significantly lower. Further, a 4-phase XFEM (based on micro-CT image) model is developed to investigate the crack propagation behaviour in both orientations. For the transverse orientation, results show that in the aged group, the crack initially follows the cementline and then penetrates the osteon, whereas, in the young group, it propagates along the cementline. These results are in agreement with experimental results where the decrease in Jgrow is more significant than the Jic in the aged group. This study suggests that ageing leads to a larger HC and reduced OWT, which weakens the crack deflection ability and causes fragility fracture. Further, the XFEM results indicate that the presence of a small microcrack in the vicinity of a major crack tip causes an increase in the critical stress intensity factor.

Prediction of mechanical properties of trabecular bone in patients with type 2 diabetes using damage based finite element method.

Type-2 diabetic (T2D) and osteoporosis (OP) suffered patients are more prone to fragile fracture though the nature of alteration in areal bone mineral density (aBMD) in these two cases are completely different. Therefore, it becomes crucial to compare the effect of T2D and OP on alteration in mechanical and structural properties of femoral trabecular bone. This study investigated the effect of T2D, OP, and osteopenia on bone structural and mechanical properties using micro-CT, nanoindentation and compression test. Further, a nanoscale finite element model (FEM) was developed to predict the cause of alteration in mechanical properties. Finally, a damage-based FEM was proposed to predict the pathological related alteration of bone's mechanical response. The obtained results demonstrated that the T2D group had lower volume fraction (-18.25%, p = 0.023), young's modulus (-23.47%, p = 0.124), apparent modulus (-37.15%, p = 0.02), and toughness (-40%, p = 0.001) than the osteoporosis group. The damage-based FE results were found in good agreement with the compression experiment results for all three pathological conditions. Also, nanoscale FEM results demonstrated that the elastic and failure properties of mineralised collagen fibril decreases with increase in crystal size. This study reveals that T2D patients are more prone to fragile fracture in comparison to OP and osteopenia patients. Also, the proposed damage-based FEM can help to predict the risk of fragility fracture for different pathological conditions.

Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes.

CONTEXT: Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status. OBJECTIVE: To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture. METHODS: Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of 2 groups, nondiabetic (n = 40) and diabetic (n = 30), with a mean duration of disease 7.5 ± 2.8 years. RESULTS: No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications-higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness. CONCLUSION: The current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia's detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness indicative of increased propensity to bone fragility.

Can High-Sensitivity C-Reactive Protein Levels Predict Functional Outcome Following Epidural Steroid Injection in Patients with Lumbar Disc Disease?

STUDY DESIGN: Prospective cohort study. PURPOSE: Inflammatory cytokines produced at the site of disc herniation are considered as pain generators in patients with lumbar disc disease. Whether a high-sensitivity C-reactive protein (hs-CRP) assay can be used in order to predict the quantum of inflammation surrounding nerve roots is a matter of investigation. This study aimed to evaluate the association of hs-CRP level and functional outcomes measured by the Modified Oswestry Low Back Pain Disability Questionnaire (MODY) before and after epidural steroid injection (ESI) in patients with lumbar disc disease. OVERVIEW OF LITERATURE: Although many studies examining the role of hs-CRP levels and lumbar pain have been published previously, the results are equivocal, and there is no clear consensus regarding which patients will benefit from an ESI. METHODS: This was a prospective study, with 77 patients in the study group and 23 participants in the control group. Baseline hs-CRP levels were obtained for both groups. Study group patients received a single ESI and were subjected to detailed pre- and postprocedure evaluation using MODY scores. For this group, hs-CRP levels were measured at 1 and 2 months after injection. RESULTS: Out of 77 patients, 52 had acute and 25 had chronic low back pain. Thirty-six patients with acute pain obtained significant improvement, while 16 had an insignificant response to the ESI. None of the chronic cases had a significant response. The mean baseline hs-CRP (mg/L) among the study group (29.83±10.43) was significantly higher than for the controls (10.26±2.783). The baseline hs-CRP among acute cases, where post ESI MODY score at 2 months had significant reduction, was 32.19±5.126, and those with insignificant reduction was 18.13±7.949 (p<0.001). CONCLUSIONS: Baseline hs-CRP levels can be used to prognosticate the outcome following ESI in patients with acute lumbar disc disease, with radicular pain refractory to physiotherapy and analgesics.

Comparative evaluation of efficacy, pharmacodynamics, and safety of Hetero's adalimumab (Mabura®, Hetero Biopharma Ltd.) and reference adalimumab (Humira®, Abbvie Inc.) in patients with active rheumatoid arthritis on concomitant methotrexate therapy.

BACKGROUND: Our study aimed to compare efficacy and safety of Hetero's adalimumab (Mabura®, Hetero Biopharma Limited) versus reference adalimumab (Humira®, Abbvie Inc.) in Indian patients with active rheumatoid arthritis (RA) concomitant on methotrexate (MTX) therapy. METHODS: Patients (n = 168) were randomized (2:1) to receive either test or reference product for 24 weeks with concomitant MTX. Proportion of patients achieving American College of Rheumatology 20 (ACR20) criteria at week 12 was the primary endpoint. Changes in Disease Activity Score of 28 joints-C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), and patients achieving ACR20 at week 24, ACR50/70 at weeks 12 and 24 were secondary endpoints. RESULTS: Patients achieving ACR20 responses with test (96.43%) were similar to reference (96.43%) in intention-to-treat (ITT) analysis at week 12. Proportional difference (PD) between groups (PD [95% CI] 0.0 [- 6.0, 6.0], p = 1.000) for ACR20 at week 12 for ITT analysis showed lower limit of the two-sided 95% CI was above the pre-specified noninferiority margin of - 15%. Similar trend in PP analysis (PD [95% CI] 0.0 [- 0.03, 0.07], p = 1.000), confirmed therapeutic equivalence. No significant difference was noted between arms for patients attaining ACR20 at week 24 and ACR50/70 at weeks 12 and 24 (all p > 0.05). DAS28-CRP and HAQ-DI were similar between groups. Total of 54 patients reported 88 AEs during the study. Out of these, 60 AEs were reported in 34 patients with Hetero-Adalimumab and 28 AEs were reported in 20 patients with Reference-Adalimumab. Total two patients, one in each group reported two serious adverse events (Sinusitis and Viral infection) during the study and resolved completely. No deaths and no life threatening AEs were reported. CONCLUSION: Results demonstrated Hetero's adalimumab is as effective and well tolerated as reference adalimumab in patients with active RA concomitantly on MTX therapy. TRIAL REGISTRATION: CTRI/2016/04/006884, Registered on 28/04/2016.

Mimicking high strength lightweight novel structures inspired from the trabecular bone microarchitecture.

Nature's evolution of a billion years has advanced flawless functionality in limitless optimized structures like bone structural adaptation in various physiological behaviours. In this study, porous structures are designed and fabricated from the nature-inspired trabecular bone microarchitecture. A three-dimensional (3D) model of the porous trabecular architecture from the compressive proximal zone of the femoral head was constructed using the micro-computed tomography scanning tool. The model was modified to get porous structures of different volume fractions varying from 20 to 40% with an increment of 10%. The obtained porous structures were 3D printed and analysed for deformation-resistant behaviour. Quasi-static compressive loading was performed at different strain rates (0.001-1 s-1) to get an insight into lightweight, high strength structural behaviour. Mechanical parameters, such as specific modulus, specific strength and specific energy absorption, were analysed for the optimal volume fraction. The original volume fraction (30%) of the trabecular bone shows the highest value of mechanical parameters. This study can help engineers to select and design lightweight porous structures with high energy-absorbing capacity, mimicking the desired architecture and porosity available in nature. This article is part of the theme issue 'Bioinspired materials and surfaces for green science and technology (part 3)'.

Preclinical Explorative Assessment of Celecoxib-Based Biocompatible Lipidic Nanocarriers for the Management of CFA-Induced Rheumatoid Arthritis in Wistar Rats.

Celecoxib (CXB), a COX-2 inhibitor, is primarily indicated for long-term treatment of rheumatoid arthritis (RA). The effective therapeutic efficacy of CXB on RA via oral administration shows adverse systemic complications, and therefore, local application of CXB has been recommended. The aim of the present study was to develop and characterize solid lipid nanoparticles (SLNs) with enhanced skin permeation potential of CXB. The particle size, polydispersity index (PDI), and percentage drug entrapment (PDE) of the developed SLNs (CXB-SLNs) were found to be 240 nm, < 0.3, and ~ 86% respectively. The developed SLNs exhibited sustained release up to 70% at the end of 48 h. Drug permeation was found to be 45% for SLN gel and 31% for conventional gel. The dermatokinetic studies also confirmed enhanced permeation of CXB in the epidermis and dermis and revealed superiority of the developed SLN gel vis-à-vis the conventional gel. Further, in the CFA-induced arthritis rat model, % arthritis index (AI) of the CXB-SLN gel formulation was found to be very less (18.54%) as compared to untreated (187.34%) and conventional gel-treated (91.61%) animals. In conclusion, the current study can provide a suitable alternative for the development of an effective topical formulation of CXB in lipid nanocarriers.

Aceclofenac cocrystal nanoliposomes for rheumatoid arthritis with better dermatokinetic attributes: a preclinical study.

AIM: The aim of present research was to complex aceclofenac with lysine (LYS) and the developed aceclofenac-LYS cocrystal was encapsulated in lipid bilayers of liposomes by employing dual carrier approach for the treatment of pain-related disorders in rheumatoid arthritis (RA). MATERIALS & METHODS: The developed carriers were characterized for particle size, drug release, ex vivo and in vivo studies, dermatokinetic modeling, complete freund's adjuvant (CFA)-induced RA rat model, radiant heat tail-flick method, formalin-induced paw-licking model, paw edema model and xylene-induced ear edema model in mice. RESULTS: The developed nanoliposomes offered nanometric size, controlled drug release and enhanced drug permeation. Further, hydrogel incorporated nanoproduct was found to be rheologically acceptable and substantially compatible with rodent skin. CONCLUSION: The studies indicated the superiority of LYS-conjugated liposome-entrapped nanocarriers for improved management of conditions like RA over the marketed product.

Emerging Advances in Nanomedicine as a Nanoscale Pharmacotherapy in Rheumatoid Arthritis: State of the Art.

There are several significant setbacks including limited bioavailability, high clearance, and further current therapies require higher and frequent dosing to gain desired therapeutic effects. Nanomedicines have been widely investigated for rheumatoid arthritis (RA). Though, higher doses also increase the incidence of dreadful adverse effects. Further, nanocarrier properties are tuned by the use of different approaches like varied methods of loading, hydrophilic polymers and targeting ligands, to change the physicochemical properties including higher encapsulation, better penetrating ability to biological barriers, thus preventing the uptake of various nanocarriers by liver and spleen. Along with these they provide longer circulation which enhances drug localization at the inflamed site and selective targeting to enhance the therapeutic index of anti-rheumatic drugs. However, the optimal properties also depend on the route of administration and nanocarrier size, thus larger size show more retention upon local injection and smaller sized ones are more optimal for passive targeting. The present review discusses the emergence of nano-carriers for anti-rheumatic drugs, which delivers drug molecule to the inflamed site by topical, intra-articular (i.a) and intra-venous (i.v) administration to achieve therapeutic efficacy by passive and active drug targeting. Advancements have been made extensively but still better investigations are needed to optimize the risk-benefit ratio for the development of safe and stable targeting nanocarriers for the effective treatment of rheumatoid arthritis (RA).

Steroid vs. Platelet-Rich Plasma in Ultrasound-Guided Sacroiliac Joint Injection for Chronic Low Back Pain.

BACKGROUND: Despite widespread use of steroids to treat sacroiliac joint (SIJ) pain, their duration of pain reduction is short. Platelet-rich plasma (PRP) can potentially enhance tissue healing and may have a longer-lasting effect on pain. OBJECTIVES: To assess the efficacy and safety of PRP compared with methylprednisolone in ultrasound-guided SIJ injection for low back pain. STUDY DESIGN: Prospective randomized open blinded end point (PROBE) study. METHODS: Forty patients with chronic low back pain diagnosed with SIJ pathology were randomly allocated into 2 groups. Group S received 1.5 mL of methylprednisolone (40 mg/mL) and 1.5 mL of 2% lidocaine with 0.5 mL of saline, while Group P received 3 mL of leukocyte-free PRP with 0.5 mL of calcium chloride into ultrasound-guided SIJ injection. Visual analog scale (VAS) scores, Modified Oswestry Disability Questionnaire (MODQ) scores, Short Form (SF-12) Health Survey scores, and complications (if any) were evaluated at 2 weeks, 4 weeks, 6 weeks, and 3 months. RESULTS: Intensity of pain was significantly lower in Group P at 6 weeks (median [interquartile range (IQR)] = 1 [1 to 1] vs. 3.5 [2 to 5]; P = 0.0004) and 3 months (Median [IQR] = 1 [1 to 3] vs. 5 [3 to 5]; P = 0.0002) as compared to Group S. The efficacy of steroid injection was reduced to only 25% at 3 months in Group S, while it was 90% in Group P. A strong association was observed in patients receiving PRP and showing a reduction of VAS ≥ 50% from baseline when other factors were controlled. The MODQ and SF-12 scores were improved initially for up to 4 weeks but deteriorated further at 3 months in Group S, while both the scores improved gradually for up to 3 months in Group P. CONCLUSION: The intra-articular PRP injection is an effective treatment modality in low back pain involving SIJ.