Evidence of bioequivalence and positive patient user handling of a tocilizumab autoinjector

Background: The anti–interleukin-6 receptor antibody tocilizumab is approved for subcutaneous injection using a prefilled syringe (PFS). We report results from a bioequivalence study in healthy subjects and a user-handling study in patients with rheumatoid arthritis (RA) using an autoinjector (AI) for tocilizumab.

Methods: A randomized crossover study in healthy subjects (N = 161) examined the bioequivalence, safety, and tolerability of tocilizumab after a single subcutaneous injection by AI versus PFS. A nonrandomized observational, real-life human factors study in RA patients (N = 54) assessed user (RA patients, caregivers, health care providers) ability to administer tocilizumab effectively by AI.

Results: Bioequivalence criteria for tocilizumab AI versus PFS were met for key pharmacokinetic parameters. Safety was comparable between devices and consistent with the established tocilizumab profile. In the real-life human factors study, the proportion of users who successfully performed all essential tasks required to operate the AI to deliver the full dose was 92.3% at first assessment and 98.1% at second assessment, with no safety concerns.

Conclusions: Tocilizumab administration by AI was bioequivalent to administration by PFS. Intended users were successful in performing the tasks required to administer tocilizumab by AI. No new safety signals were observed in either study.

Clinical Trial Registration: NCT02678988, NCT02682823     

Optimisation of the microencapsulation of lavender oil by spray drying

Background: Lavender oil consists of around 100 components and is susceptible to volatilisation and degradation reactions.

Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated.

Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography–mass spectrometry.

Results: Lavender microparticles of size 12.42?±?1.79?µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12?mg w/w%), and encapsulation efficiency (77.89 w/w%).

Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend.     

Lidocaine medicated plaster,an additional potential treatment option for localized post-surgical neuropathic pain: efficacy and safety results of a randomized,placebo-controlled trial

Objective: To assess the efficacy and safety of lidocaine 700?mg medicated plaster (lidocaine plaster) compared to placebo in patients with moderate to severe chronic post-surgical neuropathic pain (PSNP).

Methods: Patients (n?=?363) with a diagnosis of PSNP for a minimum of 3?months to 36?months were randomized (1:1) to lidocaine plaster or placebo for a 12 week double-blind treatment period. Randomization was stratified as “plaster-only” (no concomitant medication for PSNP) or as “add-on” (stable systemic medication for PSNP). The primary efficacy endpoint was the change from baseline in 24?hour average pain intensity at Week 12, assessed by 11?point numerical rating scale (NRS). The trial was registered in ClinicalTrials.gov (NCT01752322) and EudraCT (2012-000347-28).

Results: Treatment with lidocaine or placebo plaster led to a clinically relevant reduction in average pain intensity. Pain reduction (least squares mean [LS mean] standard error [SE], [95% confidence interval, CI]) with lidocaine plaster (?1.70 [0.16], [?2.03, ?1.38]) was numerically higher than with placebo (?1.47 [0.16], [?1.78, ?1.15]) but the difference was not statistically significant (?0.23 [0.23], [?0.69, 0.22]). Pre-specified exploratory subgroup analyses showed the largest differentiation between lidocaine and placebo in patients without concomitant pain medication, and in patients with more than 1?year between surgery and enrollment. Many secondary outcomes showed a numerically larger improvement in favor of lidocaine. The most commonly reported adverse events were administration site reactions linked to topical administration.

Conclusions: A clinically relevant pain reduction was observed with lidocaine plaster in patients with PSNP. The safety and tolerability profile is consistent with current knowledge.     

Impact of cigarette smoking on kidney inflammation and fibrosis in diabetic rats

Background: Cigarette smoking is a very common habit worldwide contributing to risk of kidney dysfunction and diabetes (DM). However, the mechanisms are unclear.

Aim: The goal of the present study was to assess the effects of cigarette smoking on kidney oxidative stress, inflammation, and remodeling in streptozotocin (STZ) rat model of diabetes.

Methods: Rats were randomized into control (intraperitoneal (i.p.) citrate buffer injection and exposure to fresh air), cigarette smoking (1?h daily for 6?d/week, citrate buffer), DM (single dose STZ 35?mg/kg i.p. and exposure to fresh air), and DM?+?smoking groups for a period of 4?weeks. Kidney biomarkers of inflammation, oxidative stress, and remodeling were measured.

Results: A significant increase in kidney to body weight ratio was observed in diabetic groups. Diabetes but not smoking increased blood urea nitrogen levels without changes in creatinine levels. Kidney levels of thiobarbituric acid substances, nitrite, endothelin-1, and C-reactive protein were increased significantly in the DM?+?smoking groups. Smoking induced GSH expression and activity of superoxide dismutase. A significant increase in kidney fibrosis was observed in the DM?+?smoking group coupled with a similar increase in transforming growth factor beta. Protein levels of matrix metalloproteinase-2, (MMP-2), mitogen-activated protein kinases, and c-Jun N terminal kinase were elevated in Smoking and DM?+?smoking groups.

Conclusion: Cigarette smoke might promote risk of kidney dysfunction in DM by augmentation of renal inflammation, oxidant radicals and fibrosis. The kidney promotes compensatory increase in MMP-2 in response to smoking probably to prevent pro-fibrotic factors induced-fibrosis.     

QAPSA: post-marketing surveillance of capsaicin 8% patch for long-term use in patients with peripheral neuropathic pain in France

Objective: To describe the characteristics of patients treated with the capsaicin 8% patch, prescribing conditions, long-term effects of repeat treatment on pain intensity and perception, quality of life, and impact on concomitant medication.

Methods: A national, longitudinal, prospective, non-interventional, post-marketing open study was conducted in 50 French pain centers. Adult volunteer non-diabetic patients with peripheral neuropathic pain receiving capsaicin 8% patch treatment were consecutively enrolled. Treatment could be repeated over a 12-month period, with 6?months’ follow-up after last application.

Results: A total of 684 patients (age: 53.0?±?14.9?years, mean?±?standard deviation; post-traumatic/surgical peripheral neuropathic pain: 76.3%; pain intensity: 6.2?±?1.7; pain duration: 3.0?years, median) were treated with 1 to 5 patches at 3/4?month intervals; 70.3% were naive to capsaicin 8% patch treatment at inclusion. Six months after last application, treatment was considered as successful for 21.8% (95% confidence interval: 17.5%–26.7%) of patients by a stringent criterion combining improvement according to the patient’s global impression of change (PGIC) and at least 30% improvement on a numerical pain rating scale (NPRS). Clinically relevant improvement in health-related quality of life was observed at end-of-study. No unexpected safety concerns were observed with capsaicin 8% patch repeat treatment.

Conclusions: The data of this post-marketing study meets the request by the French authorities for additional data on conditions of use in everyday practice. They confirmed the tolerance and long-term effect of capsaicin 8% patch in patients with peripheral neuropathic pain in real-world conditions.     

A randomized,double-blind,placebo-controlled study of once weekly elcatonin in primary postmenopausal osteoporosis

Objective: Very few reports have described changes in bone mineral density (BMD) with long-term, once weekly administration of elcatonin, and its effects in reducing incident fractures remain unverified. Therefore, the efficacy and safety of once weekly elcatonin were examined over a 3?year period.

Methods: This was a multicenter, double-blinded, randomized, placebo-controlled study. Postmenopausal women with primary osteoporosis received either 20?units of elcatonin (EL group, n?=?433) or placebo (P group, n?=?436) once a week for 144?weeks (3?years) intramuscularly. The primary endpoint was the incidence of new vertebral fractures at 24, 48, 72, 96, 120, and 144?weeks after the start. Secondary endpoints were the incidence of non-vertebral fractures, changes in lumbar, hip total and femoral neck BMD, and the incidence of adverse drug reactions (ADRs).

Results: No significant reduction in the incidence of new vertebral fractures was found in the EL group. The percentage increase in lumbar BMD was significantly higher in the EL group from 24?weeks to the last administration. Although the EL group showed tendencies toward smaller decreased hip total and femoral neck BMD, no significant differences were observed between groups. The incidence of ADRs was significantly greater in the EL group, although these have all been previously reported and no new safety concerns were identified.

Conclusions: Once weekly injection of 20?units of elcatonin significantly increased lumbar BMD over a 3?year period and did not cause any safety problems, but no significant reduction in the incidence of vertebral or non-vertebral fractures was demonstrated.     

Efficacy and safety of CKD-11101 (darbepoetin-alfa proposed biosimilar) compared with NESP in anaemic chronic kidney disease patients not on dialysis

Objective: To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP® in treatment of anaemia in patients with chronic kidney disease not on dialysis. Clinical Trial Registration: NCT03431623.

Method: In this multi-centre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24?weeks, during which patients were treated every 2?weeks. All patients who completed the EEP were treated with CKD-11101 every 2?weeks for the first 4 weeks and every 4?weeks for the safety evaluation period (SEP), which was from 24?weeks to 52?weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb.

Results: The mean Hb level was increased in both groups during the EEP (both p?<?0.001). The difference in mean Hb level change between the two groups was 0.01?g/dL (95% CI = –0.213–0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was –1.40?mcg (95% CI = –6.859–4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group).

Conclusion: CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.     

Study description and baseline characteristics of the population enrolled in a multinational,observational study of teriparatide in postmenopausal women with osteoporosis: the Asia and Latin America Fracture Observational Study (ALAFOS)

Objective: To describe the study design and baseline patient characteristics of the Asia and Latin America Fracture Observational Study (ALAFOS) to better understand the profile of patients receiving teriparatide during the course of routine clinical practice in Asia, Latin America, the Middle East and Russia.

Methods: Prospective, observational, non-interventional study in postmenopausal women with osteoporosis who are prescribed teriparatide for up to 24?months, according to local medical standards, with a 12?month post-treatment follow-up.

Measures: Demographics, risk factors for osteoporosis and fractures, history of fracture, prior osteoporosis medications, comorbidities, physical function, back pain and quality of life (QoL).

Results: In total 3031 postmenopausal women (mean age 72.5?years) recruited at 152 sites in 20 countries were analyzed; 62.9% had a history of fragility fracture after age 40 (33.0% of patients with spinal, 14.2% with hip fractures). The mean (SD) bone mineral density T-scores at baseline were ?3.06 (1.40) and ?2.60 (1.05) at the lumbar spine and femoral neck, respectively. At entry, 43.7% of patients were naïve to prior osteoporosis treatments; 40.5% of patients reported ≥1 fall in the past year. The median (Q1; Q3) EuroQoL Visual Analog Scale (EQ-VAS) for perceived overall health status was 60 (50; 80). The mean (SD) worst back pain Numeric Rating Scale in the last 24?hours was 4.6 (3.3).

Conclusions: Our data indicates that patients who were prescribed teriparatide in the ALAFOS participant countries had severe osteoporosis, high prevalence of fractures, disabling back pain and poor QoL. The frequency of patients receiving prior osteoporosis medications was lower than in previous observational studies conducted in other locations.     

Comparative efficacy of first-line ceritinib and crizotinib in advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer: an adjusted indirect comparison with external controls

Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.

Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI])?=?0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value?=?0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.

Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC.     

An evaluation of peripapillar choroidal thickness in patients receiving systemic isotretinoin treatment

Purpose: Oral isotretinoin (13-cis retinoic acid, 13-cis RA) was approved for severe acne treatment by the FDA in 1982. The ocular side effects associated with oral isotretinoin use are mostly dose-dependent. Numerous ocular pathologies affect peripapillary choroidal layer primarily or indirectly.

Objective: Evaluation of the peripapillary choroidal layer in the patients receiving oral isotretinoin therapy may aid in explaining the pathophysiology of ocular side effects.

Methods: In this study, peripapillary choroidal thickness was assessed in the patients receiving oral isotretinoin treatment via optical coherent tomography technique.

Results: Significant difference was found in the superotemporal and temporal areas.

Conclusion: Oral isotretinoin treatment may affect the thickness of the peripapillary choroidal layer.     

A review of dexketoprofen trometamol in acute pain

Objective: Dexketoprofen trometamol is a modified non-selective COX inhibitor with a rapid onset of action that is available as both oral and parenteral formulations. The aim of this narrative review was to assess the efficacy and tolerability/safety of dexketoprofen trometamol in acute pain states using the best available published scientific evidence (randomized controlled clinical trials and systematic reviews/meta-analyses).

Methods: Literature retrieval was performed via Medline, Embase and the Cochrane Library (from inception up to March 2017) using combinations of the terms “randomized controlled trials”, “dexketoprofen”, “celecoxib”, “etoricoxib”, “parecoxib” and “acute pain”.

Results: Single-dose dexketoprofen trometamol provides effective analgesia in the treatment of acute pain, such as postoperative pain (dental and non-dental surgery), renal colic, acute musculoskeletal disorders and dysmenorrhea, and reduces opioid consumption in the postoperative setting. It has a rapid onset of action (within 30?minutes) and is well tolerated during short-term treatment. Direct comparisons with COX-2 inhibitors are lacking; however, the efficacy and tolerability of single-dose dexketoprofen trometamol appears to be consistent with that seen with celecoxib, etoricoxib and parecoxib in the acute pain setting.

Conclusion: In conclusion, dexketoprofen trometamol appears to provide similar analgesic efficacy to COX-2 inhibitors when used to treat acute pain, has a rapid onset of action, is well tolerated, and has an opioid-sparing effect when used as part of a multimodal regimen in the acute pain setting.     

Effectiveness and safety of micronized purified flavonoid fraction for the treatment of concomitant varicose veins of the pelvis and lower extremities

Objective: Concomitant varicose veins of the pelvis (VVP) and lower extremities (VVLE) frequently coexist. This study evaluated the effectiveness and safety of micronized purified flavonoid fraction (MPFF) in the treatment of patients with both conditions.

Methods: Female outpatients with concomitant VVP and VVLE received MPFF 1000?mg once daily for 2 months (Group 1), or 1000?mg twice daily for 1 month followed by 1000?mg once daily for 1 month (Group 2), based on pelvic pain intensity. Change in pain intensity during treatment was evaluated on a 10?cm visual analog scale. All patients underwent transvaginal and transabdominal duplex ultrasound scanning, radionuclide phlebography of the lower extremities, and emission computer tomography of the pelvic veins at inclusion and end of treatment.

Results: In Group 1 (N?=?35), MPFF was associated with a twofold reduction in pain syndrome severity (pelvic, perineal and lower leg pain) in all patients after 1 month, and a reduction in chronic pelvic pain (CPP) from 3.4?±?1.2 to 0.83?±?0.18?cm at 2 months. Leg pain significantly decreased from 2.8?±?0.6 at baseline to 0.94?±?0.11 after 2 months. In Group 2 (N?=?30), MPFF decreased CPP severity from 6.3?±?0.8 to 1.2?±?0.12, perineal pain from 3.6?±?0.9 to 0.88?±?0.22 and leg pain from 4.6?±?0.5 to 0.9?±?0.1. Radionuclide phlebography confirmed the clinical improvement in both treatment groups, with a substantial increase in linear blood flow velocity in the internal iliac veins (～10% in Group 1 and 35% in Group 2) and a reduction in mean transit times of the radiopharmaceutical. MPFF also reduced blood stasis in the pelvic venous plexuses. Gastralgias were reported in two patients but resolved rapidly and did not lead to treatment withdrawal.

Conclusion: Phlebotropic treatment with MPFF is an effective and safe method of conservative therapy in patients with concomitant VVP and VVLE.     

Evaluation of the amount of nanoparticles emitted in LASER additive manufacture/welding

Objectives: The objective of this study was the evaluation of the professional exposure to nanoparticles during tasks performed in workstations for production of metallic parts by laser welding additive manufacturing.

Materials and methods: The study was developed in an installed additive manufacturing machine, having controlled temperature and humidity in an industrial unit where metal parts were being produced using stainless steel powders of granulometry of 10 to 35?μm.

Results and discussion: Monitoring of airborne nanoparticles emission was made using adequate equipment, which showed considerable number of nanoparticles over the baseline, having the same composition as the steel powder used.

Conclusion: It is concluded that the values of professional exposure to nanoparticles are high in these workstations and that the nanoparticles to which the workers are exposed are small in size (around 15?nm), thus having a strong capacity for alveolar penetration and, consequently, with a strong possibility of passing to the bloodstream, accumulating in the body.     

Comparative efficacy of brigatinib versus ceritinib and alectinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell lung cancer

Objective: Brigatinib, ceritinib, and alectinib are approved to treat crizotinib-refractory anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC), but no trial has compared them head-to-head. A matching-adjusted indirect comparison (MAIC) was conducted to estimate the relative efficacy of these agents in the crizotinib-refractory setting.

Methods: MAIC is a propensity score-type method that adjusts for differences in baseline characteristics between trials to estimate relative efficacy. Analyses were based on patient-level data from the ALTA trial for brigatinib and published summary-level trial data from ASCEND-1 and ASCEND-2 for ceritinib and NP28761 and NP28673 for alectinib. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared.

Results: After matching, all key baseline characteristics were balanced between trials. Compared with ceritinib, brigatinib was associated with longer PFS (ASCEND-1: median 15.7 vs 6.9 months, hazard ratio (HR) [95% confidence interval]?=?0.38 [0.26–0.57]; ASCEND-2: median?=?18.3 vs 7.2 months, HR?=?0.33 [0.20–0.56]) and OS (ASCEND-1: not available; ASCEND-2: median 27.6 vs 14.9 months, HR?=?0.33 [0.17–0.63]). Versus alectinib, brigatinib was associated with longer PFS (NP28761: median?=?17.6 vs 8.2 months, HR?=?0.56 [0.36–0.86]; NP28673: median?=?17.6 vs 8.9 months, HR?=?0.61 [0.40–0.93]); results for OS were inconclusive (NP28761: median?=?27.6 vs 22.7 months, HR?=?0.70 [0.42–1.16]; NP28673: median?=?27.6 vs 26.0 months, HR?=?0.66 [0.39–1.09]). ORR was similar.

Conclusion: In crizotinib-refractory ALK?+?NSCLC patients, relative efficacy estimates suggest brigatinib may have prolonged PFS and OS vs ceritinib and prolonged PFS vs alectinib.     

A randomized controlled trial comparing tapentadol with oxycodone in non-breastfeeding women post elective cesarean section

Background: Tapentadol may allow greater pain relief with reduced “opioid load” compared to oxycodone. Its use has not been studied in the obstetric population. The objective of this study was to compare the efficacy and side effect profile of tapentadol with oxycodone in patients who received spinal anesthesia for elective cesarean section. The trial was registered with EU Clinical Trials Register with CT number 2016-001621-33.

Methods: This was a multicenter, randomized controlled trial. Randomized patients (n?=?68) received either 50?mg tapentadol or oxycodone 10?mg 12 hourly postoperatively. The primary endpoint was the sum of pain intensity difference over the first 48?hours of treatment (SPID₄₈). Secondary outcomes included time to rescue medications, SPID₃₆, total pain relief (TOTPAR) scores, patient satisfaction scores, sum of total pain relief and pain intensity difference (SPRID) scores, time to rescue medications and side effects experienced. An analysis of covariance model with baseline pain intensity score as a covariate was used for statistical analysis.

Results: There was no significant difference in the primary endpoint of SPID₄₈ with adjusted mean difference -11.45 (95% CI -35.35, 12.45) p?=?.34). Oxycodone showed significantly greater SPID₃₆ scores compared to tapentadol with increased time to rescue medication. Side effects experienced were similar between groups.

Conclusion: Tapentadol did not provide superior pain control or improved tolerability compared to oxycodone post cesarean section. Results should be interpreted however with consideration of administration of intrathecal opioids to all patients in this study and debate over the optimal dose of tapentadol for acute pain.     

Greater occipital and supraorbital nerve blockade for the preventive treatment of migraine: a single-blind,randomized, placebo-controlled study

Objective: Nerve injections have been used for the acute and preventive treatment of migraine in recent decades. Most of these injections focused on greater occipital nerve (GON) blockade. However, few studies were placebo controlled, and only a few of them investigated GON and supraorbital nerve (SON) blockade together. This study aimed to evaluate the efficacy of GON and SON blockade with local anesthetics for the preventive treatment of migraine without aura.

Methods: Eighty-seven patients diagnosed with migraine without aura were included in the study. Patients were divided randomly. One group was injected with 1% lidocaine, the other group was injected with 0.9% saline. GON and SON injections were done bilaterally. The injections were repeated weekly for 3 weeks. Patients were followed up for 2 months to assess clinical response.

Results: Seventy-one patients completed the study. After 2 months, the number of headache days decreased significantly from 12.8?±?10.9 to 5.3?±?7.4, and VAS decreased from 8.3?±?1.0 to 5.5?±?1.9 in the blockade group. The number of headache days decreased from 12.4?±?10.3 to 7.5?±?7.2 and VAS decreased from 8.2?±?1.1 to 7.4?±?1.3 in the placebo group. Response was seen in 65.1% of the patients in the blockade group (65.4% for episodic migraine, 64.7% for chronic migraine) and 28.6% of the patients in the placebo group. The difference was significant.

Conclusions: The results suggest that GON and SON blockade with lidocaine was more effective than the placebo in the prophylactic treatment of both episodic and chronic migraine.     

Insulin-like growth factor-1 (IGF-1) poly (lactic-co-glycolic acid) (PLGA) microparticles – development,characterisation, and in vitro assessment of bioactivity for cardiac applications

Aim: The aim of this study was to evaluate the formulation of a synthetic IGF-1 (pIGF-1) in PLGA microparticles (MP).

Methods: Poly (lactic-co-glycolic acid) (PLGA) MPs loaded with pIGF-1 were prepared, characterised and evaluated using double emulsion solvent evaporation method.

Results: Spherical MPs showed an average particle size of 2?µm, encapsulation efficiency (EE) of 67% and 50% degradation over 15?days. With a view to enhancing retention in the myocardium, the MP formulation was encapsulated in a cross-linked hyaluronic acid hydrogel. pIGF-1 released from MPs and from MPs suspended in hyaluronic acid hydrogel remained bioactive, determined by a significant increase in cellular proliferation of c-kit⁺ cells.

Conclusion: This formulation has potential for loco-regional delivery to damaged myocardium to promote the survival of cardiomyocytes.     

Comparison of a twice daily injection of insulin aspart 50 with insulin aspart 30 in patients with poorly controlled type 2 diabetes

Objective: To compare the efficacy and safety of a twice daily injection of insulin aspart (BIAsp) 30 and BIAsp50 in patients with type 2 diabetes mellitus (T2DM) poorly controlled with oral hypoglycemic agents (OHAs).

Methods: In this 12 week prospective, randomized, parallel trial, a total of 80 T2DM patients, 59?±?10?years old with a disease duration of 9.3?±?6.6?years and HbA1c >7% despite large doses of metformin and sulfonylurea administration, were randomized to receive BIAsp30 (n?=?40) or BIAsp50 (n?=?40). The primary endpoint was a change in HbA1c at week 12.

Results: The changes in HbA1c from baseline were ?2.5%?±?1.0% in the BIAsp50 group and ?2.5%?±?1.2% in the BIAsp30 group (p?=?.897). No difference was observed in the rate of HbA1c target achievement (<7.0%) between BIAsp50 (42.5%) and BIAsp30 (32.5%) (p?=?.495). The change in fasting plasma glucose (FPG) in the BIAsp50 group was lower than that in the BIAsp30 group (p?<?.001), while the change in two-hour postprandial blood glucose (2hPBG) was higher and blood glucose excursion was lower in the BIAsp50 group than that in the BIAsp30 group (p?<?.001, p?<?.001). A significant improvement in HbA1c was observed with BIAsp50 in subgroups with baseline blood glucose excursion >7.8?mmol/L or 2hPBG >17.6?mmol/L compared with BIAsp30. There were no differences in hypoglycemia or body weight between groups.

Conclusions: Compared with BIAsp30, BIAsp50 showed greater efficacy in patients with baseline BG excursion >7.8?mmol/L or 2hPBG >17.6?mmol/L as well as good safety for hypoglycemia.

Clinical trial registration: ChiCTR-IIR-16008958.     

In vivo study of mPEG–PCL as a nanocarriers for anti-inflammatory drug delivery of simvastatin

Purpose: In this study, methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG–PCL) di-block copolymers were synthesized. The purpose of this work is to investigate the in vivo anti-inflammatory effects of simvastatin-loaded micelles.

Methods: The structure of synthesized copolymers was characterized by using HNMR, FTIR, and GPC techniques. Simvastatin was encapsulated in micelles through a single-step nano-precipitation method, leading to the formation of simvastatin-loaded mPEG–PCL (simvastatin-mPEG–PCL) micelles. In this study, the anti-inflammatory effects of simvastatin/mPEG–PCL micelles versus indomethacin were investigated in acute inflammation-induced rats. The paw edema thickness was measured 1, 2, 3, and 4?h after injection of formulation. The inhibition of edema in various groups were calculated and reported by percentages.

Results: The results showed that the zeta potential of micelles was about ?14.9?±?0.47?mV and the average size was in range of 66.10?±?0.34?nm. Simvastatin was encapsulated in mPEG–PCL micelles with a loading capacity of 9.63?±?0.87% and an encapsulation efficiency of 64.20?±?0.79%. Simvastatin and simvastatin-mPEG–PCL micelles showed significant anti-inflammatory activity in the present study.

Conclusions: This study revealed that simvastatin and simvastatin/mPEG–PCL micelles both have anti-inflammatory effects and suggested that statins have potential anti-inflammatory activity along with their lipid lowering properties.