Pilocarpine Research Articles

Hypothermia Reduces Mortality, Prevents the Calcium Plateau, and Is Neuroprotective Following Status Epilepticus in Rats.

Status Epilepticus (SE) is a major neurological emergency and is considered a leading cause of Acquired Epilepsy (AE). We have shown that SE produces neuronal injury and prolonged alterations in hippocampal calcium levels ([Ca2+]i) that may underlie the development of AE. Interventions preventing the SE-induced Ca2+ plateau could therefore prove to be beneficial in lowering the development of AE after SE. Hypothermia is used clinically to prevent neurological complications associated with Traumatic Brain Injury, cardiac arrest, and stroke. Here, we investigated whether hypothermia prevented the development of Ca2+ plateau following SE. SE was induced in hippocampal neuronal cultures (HNC) by exposing them to no added MgCl2 solution for 3 h. To terminate SE, low Mg2+ solution was washed off with 31°C (hypothermic) or 37°C (normothermic) physiological recording solution. [Ca2+]i was estimated with ratiometric Fura-2 imaging. HNCs washed with hypothermic solution exhibited [Ca2+]i ratios, which were significantly lower than ratios obtained from HNCs washed with normothermic solution. For in vivo SE, the rat pilocarpine (PILO) model was used. Moderate hypothermia (30–33°C) in rats was induced at 30-min post-SE using chilled ethanol spray in a cold room. Hypothermia following PILO-SE significantly reduced mortality. Hippocampal neurons isolated from hypothermia-treated PILO SE rats exhibited [Ca2+]i ratios which were significantly lower than ratios obtained from PILO SE rats. Hypothermia also provided significant neuroprotection against SE-induced delayed hippocampal injury as characterized by decreased FluoroJade C labeling in hypothermia-treated PILO SE rats. We previously demonstrated that hypothermia reduced Ca2+ entry via N-methyl-D-aspartate and ryanodine receptors in HNC. Together, our studies indicate that by targeting these two receptor systems hypothermia could interfere with epileptogenesis and prove to be an effective therapeutic intervention for reducing SE-induced AE.

The Synergistic Effect of Raloxifene, Fluoxetine, and Bromocriptine Protects Against Pilocarpine-Induced Status Epilepticus and Temporal Lobe Epilepsy.

The present antiepileptic drugs pose several problems in the management of seizures owing to their meager neuroprotective potential, adverse effects on bone, detrimental effects on cognitive function, chronic toxicity, drug interactions, side effects including aggression, agitation, and irritability and sometimes exacerbation of seizures. We followed up progressive preclinical investigation in mice against pilocarpine (PILO)-induced status epilepticus (SE) and temporal lobe epilepsy (TLE). To determine the response of raloxifene (RF) (4 and 8mg/kg), fluoxetine (FT) (14 and 22mg/kg), bromocriptine (BC) (6 and 10mg/kg), and their low-dose combinations, oral treatment was scheduled for 28days followed by PILO (300mg/kg, i.p). The response was stalked for intensive behavioral monitoring of convulsions, hippocampal neuropeptide Y (NPY), and oxidative stress discernment along with histomorphological studies. The resultant data confirmed the therapeutic potential of triple drug combination of raloxifene (4mg/kg) with fluoxetine (14mg/kg) and bromocriptine (6mg/kg) compared to monotherapy with raloxifene (4mg/kg), and bromocriptine (6mg/kg) as otherwise monotherapy with fluoxetine (14mg/kg) was ineffective to suppress convulsions; an effect better than sodium valproate (300mg/kg), a standard AED, was validated. Most profoundly, PILO-induced compensatory increases in hippocampal NPY levels (20.01%), which was escalated (100%) with the triple drug combination. The same pattern of results was superseded for oxidative stress indices and neuronal damage. The results for the first time demonstrate the propitious role of triple drug combination in the management of SE and TLE. Therapeutically, this enhancing profile of drugs fosters a safer and more effective drug-combination regimen. Graphical abstract.

Gamma-Decanolactone Improves Biochemical Parameters Associated with Pilocarpine-Induced Seizures in Male Mice.

Gamma-decanolactone (GD) is a monoterpene effective against seizures induced by pentylenetetrazole. The mechanism of action of GD is likely to be via glutamate antagonism. GD also inhibits intracellular reactive oxygen species (ROS) generation and the lipopolysaccharide-induced expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) in vitro. Considering the neuropharmacological profile of GD studied so far, we investigated the effect of intraperitoneal administration of GD 100 and 300 mg/kg on pilocarpine (PIL)-induced status epilepticus (SE) in mice. GD was administered 30 min before PIL. Behavioral (latency to first seizure and the percentage of clonic forelimb seizures), biochemical, and oxidative stress parameters were evaluated. DNA damage in the cerebral cortex of mice was assessed using the comet assay and mutagenic activity of GD was evaluated using Salmonella/microsome assay in TA100, TA98, TA97a, TA102, and TA1535 strains, with and without metabolic activation (S9 mix). The behavioral results showed that only the latency to the first clonic seizure increased in the groups treated with GD 300 mg/kg, but not when the animals received GD 100 mg/kg. Both GD doses were able to increase superoxide dismutase and catalase activities, inducing a decrease in ROS and nitrite production and in DNA damage in the cerebral cortex. GD was not able to induce base pair substitution and frameshift mutations in the absence or in the presence of metabolic activation. These findings demonstrate that GD does not improve behavioral parameters in the PIL model, but it was able to protect seizure-related oxidative stress and DNA damage in mice, without inducing gene mutations.

Safranal carried by nanostructured lipid vehicles inhibits generalized epilepsy in mice.

Safranal, a main component of Crocus sativus, is suggested to have neuroprotective effects. The aim of this study was to investigate the effect of safranal and nanostructured lipid vehicle (NLV) carried safranal in acute and chronic experimental mice models of epilepsy. In PILO acute seizure model, safranal dose-dependently extended latency to generalized seizure, decreased the highest seizure stages and the number of generalized seizures. Moreover, NLV carried safranal further enhanced the anti-seizure effect, which is comparable to the action of sodium valproate. Meanwhile, NLV carried safranal reduced and delayed the electroencephalogram spectra power after pilocarpine injection. In histological aspect, safranal dose-dependently reduced the loss of neurons induced by seizure and NLV system further improved this protection at the same dose. In MES acute model, safranal markedly increased the electroconvulsive threshold, where NLV further improved its effect. In PTZ chronic seizure model, NLV carried safranal significantly delayed the kindling rate of progress and the time it took to reach generalized seizures as compared to NLV control group. In conclusion, this study indicates that safranal inhibits generalized seizure in acute and chronic epilepsy models in mice and NLV can enhance this effect. So, NLV carried safranal may have potential value in treatment of generalized epilepsy.

Antiepileptic effect of uridine may be caused by regulating dopamine release and receptor expression in corpus striatum

Uridine is a potential endogenous neuromodulator studied for several decades for its antiepileptic effect, but the results were controversial. One remarkable feature of uridine is its regulatory action on the dopaminergic pathways. In this study, the changes in uridine and dopamine (DA) release were examined in the mouse corpus striatum after pilocarpine (PC) intraperitoneal injection. Then, the effect of uridine pre-treatment on DA release and expression of dopamine receptor (DR) was determined. The results revealed an increased uridine release initially, followed by a downward trend after an injection of 400-mg/kg PC. However, the DA release continuous increased significantly. The expression of dopamine receptor-1 (D1R) increased in a dose-dependent manner while that of dopamine receptor-2 (D2R) decreased significantly. Prophylactic administration of uridine significantly relieved the high-frequency and high-amplitude expression induced by PC as well as dose-dependently reversed the PC-induced changes in DA and DRs levels. These findings suggested that uridine produced an antiepileptic effect, which might have been mediated in part by interfering with the dopaminergic system.

New low-dose liquid pilocarpine formulation for treating dry mouth in Sj\xf6gren\u2019s syndrome: clinical efficacy, symptom relief, and improvement in quality of life

BackgroundPatients with Sjögren’s syndrome (SS) typically present clinically with xerostomia (dry mouth) because of progressive damage to the exocrine glands. We developed a new, low-dose pilocarpine/sodium alginate (LPA) solution with pilocarpine hydrochloride to inhibit systemic adverse effects by administering via the oral mucosa. The purpose of this study was to assess its stability, safety, and efficacy.MethodsThe pilocarpine concentration in an LPA liquid formulation was measured 3, 7, 14, and 28 days after preparation to assess its stability. A prospective clinical trial was undertaken to assess the efficacy and safety of the LPA solution as a symptomatic treatment for dry mouth in SS. Patients (n = 24) with clinically significant xerostomia were enrolled after providing written informed consent. Whole-mouth salivary flow rate was measured twice; immediately before and 60 min after LPA application. Symptoms were assessed by questionnaire with visual analog scales or checkboxes before the first application (baseline), and then once daily for 7 days.ResultsThe pilocarpine content 3, 7, 14, and 28 days after preparation showed no marked change, confirming its stability. Salivary flow was significantly increased from 0.076 ± 0.092 g/30 s to 0.122 ± 0.140 g/30 s 60 min after LPA administration (P < 0.001). Dry mouth and thirstiness showed significant improvement compared with that of baseline (P ≤ 0.01). The only adverse effect was sweating, and no serious drug-related adverse events were reported.ConclusionsThis new, low-dose pilocarpine formulation was well-tolerated and resulted in significant improvements in symptoms of dry mouth and other xerostomic conditions in patients with SS.Trial registrationThe study approval number in the institution; 08–068-2. Registered January 19, 2009. UMIN000029307. Registered 27 September 2017 (retrospectively registered).

Axial elongation measured by long scan depth optical coherence tomography during pilocarpine-induced accommodation in intraocular lens-implanted eyes

We used an ultra-long scan depth optical coherence tomography (UL-OCT) system to investigate changes in axial biometry of pseudophakic eyes during pilocarpine- induced accommodation. The right eyes from 25 healthy subjects (age range 49 to 84 years) with an intraocular lens (IOL) were imaged twice in the non-accommodative and the accommodative states. A custom-built UL-OCT instrument imaged the whole eye. Then accommodation was induced by two drops of 0.5% pilocarpine hydrochloride separated by a 5-minute interval. Following the same protocol, images were acquired again 30 minutes after the first drop. The central corneal thickness (CCT), anterior chamber depth (ACD), IOL thickness (IOLT), and vitreous length (VL) were obtained using custom automated software. The axial length (AL) was calculated by summing the CCT, ACD, IOLT, and VL. With accommodation, ACD increased by +0.08 ± 0.09 mm, while the VL decreased by −0.04 ± 0.09 mm (paired t-test each, P<0.05). CCT and IOLT remained constant during accommodation (P > 0.05). The non-accommodative AL was 23.47 ± 0.93 mm, and it increased by +0.04 ± 0.04 mm after accommodation (P<0.01). The AL increased and the IOL moved backward during pilocarpine-induced accommodation in pseudophakic eyes.

First HPLC method for the simultaneous quantification of levetiracetam, zonisamide, lamotrigine, pentylenetetrazole and pilocarpine in rat plasma and brain

A new HPLC-DAD method is herein reported for the first time for the simultaneous determination of three antiepileptic drugs [levetiracetam (LEV), zonisamide (ZNS) and lamotrigine (LTG)] and two convulsant agents [pentylenetetrazole (PTZ) and pilocarpine (PIL)] in rat plasma and brain matrices.

Effect of pilocarpine hydrochloride for the treatment of oral discomfort with decreased saliva production

Effect of pilocarpine hydrochloride for the treatment of oral discomfort with decreased saliva production

A Pilot Study on the Modified Multiple Divided Dosing of Pilocarpine Hydrochloride for Paient Suffered from Xerostomia Due to Sjögren’s Syndrome

A Pilot Study on the Modified Multiple Divided Dosing of Pilocarpine Hydrochloride for Paient Suffered from Xerostomia Due to Sjögren’s Syndrome

Preparation Pilocarpine Hydrochloride Selective Electrodes

New eight selective electrodes of pilocarpine hydrochloride deepened on complexes of (PCH) -molybdophosphoric acid and (PCH) – phosphotungstate were prepared with varied plasticizers. Electrode with complex (DBPH-MP) was used as an active material, gave linear range from 5.0×10-2 to 6.0×10-5 M, and slope was 62.01 mV/decade, with detection limit was 2.0×10-5M, lifetime was near to 60 days. Electrode,s membrane made with active material (DBP-MP), showed concentration range was 2.1×10-3-6.3×10-5M, the slope was near to 52.34 mV/decade. Detection limit was 1.0×10-5M, 55 days was the life time of this electrode. The parameters of electrode deepened on (DBPH-PT), concentration range was from 5.0×10-2 to 6.5×10-5 M with slope 50.41 mV/decade, 2.2×10-5 M was the detection limit.Life time was determined around to 52 days.

In Vivo Monitoring for Regional Changes of Metabotropic Glutamate Receptor Subtype 1 (mGluR1) in Pilocarpine-Induced Epileptic Rat Brain by Small-Animal PET

Metabotropic glutamate receptor subtype 1 (mGluR1) is a crucial pharmacological target for several central nervous system disorders. In this study, we aimed to monitor in vivo regional changes of mGluR1 related to neuroinflammation in the brains of rats after pilocarpine-induced status epilepticus (PISE) using longitudinal positron emission tomography (PET). PISE was induced in rats by administering lithium chloride, followed by repeated pilocarpine hydrochloride treatments. PET assessments were conducted using N-[4-[6-(isopropylamino)-pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[11C]methylbenzamide ([11C]ITDM), a selective radioligand for mGluR1, and N-benzyl-N-[11C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC), a selective translocator protein PET ligand for neuroinflammation monitoring. PET scans were conducted on PISE rats at 1 day (acute), 1 week (subacute) and 3 weeks (chronic) after repeated seizures. PET with [11C]ITDM showed significant decreases of mGluR1 availability (BPND) in the thalamus and hippocampus after PISE over the chronic period. Conversely, PET with [11C]DAC exhibited a significant increase of radioactive uptake in the forebrain after the acute period, especially in the thalamus. These conflicting changes in the thalamus indicated negative correlation. In conclusion, PET with [11C]ITDM could successfully visualize hippocampal and thalamic declines of mGluR1 related to neuroinflammation, which would help further understanding for mGluR1 functions in neuroexcitotoxicity.

Evaluation of metformin effects in the chronic phase of spontaneous seizures in pilocarpine model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360mg/kg to induce status epilepticus (SE). At 45day after induction of SE, metformin was injected intraperitoneally in dose of 250mg/kg/day for 5days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB). We have shown that this reduced expression pattern is mediated by the transcriptional co-repressor CtBP (C-terminal binding protein). Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway. Our findings have been shown that metformin has anticonvulsant and antiepileptic properties, and suggesting that antiglycolytic compounds such as metformin may represent a new class of drugs for treating epilepsy.

Anticonvulsant effects of Senna spectabilis on seizures induced by chemicals and maximal electroshock

Senna spectabilis (Fabaceae) is one of the medicinal plants used in Cameroon by traditional healers to treat epilepsy, constipation, insomnia, anxiety. The present study aimed to investigate the anticonvulsant effects of Senna spectabilis decoction on seizures induced by maximal electroshock (MES), pentylenetetrazole (PTZ), pilocarpine (PC) and its possible action mechanisms in animal models using flumazenil (FLU), methyl-ß-carboline-3-carboxylate (BC) and bicuculline (BIC). Senna spectabilis decoction (106.5 and 213.0mg/kg) antagonized completely tonic-clonic hind limbs of mice induced by MES. The lowest plant dose (42.6mg/kg) provided 100% of protection against seizures induced by PTZ (70mg/kg). Administration of different doses of the plant decoction antagonized seizures induced by PC up to 75%, causing a dose dependent protection and reduced significantly the mortality rate induced by this convulsant. Both FLU and BC antagonize strongly the anticonvulsant effects of this plant and are unable to reverse totally diazepam or the plant decoction effects on inhibiting seizures. The animals did not present any sign of acute toxicity even at higher doses of the plant decoction. In conclusion, Senna spectabilis possesses an anticonvulsant activity. We showed that its decoction protects significantly mice against seizures induced by chemicals and MES, delays the onset time and reduces mortality rate in seizures-induced. It also appears that the oral administration of the decoction of S. spectabilis is more active than the intraperitoneal administration of the ethanolic extract on inhibiting seizures induced by MES and PTZ. Moreover, the plant decoction could interact with GABAA complex receptor probably on the GABA and benzodiazepines sites.

Pure Glaucoma Drugs Are Toxic to Immortalized Human Corneal Epithelial Cells, but They Do Not Destabilize Lipid Membranes.

Most pure glaucoma drugs (pGDs) are hydrophobic substances intended to reduce elevated intraocular pressure. The aims of our study were to determine the toxicity of pGDs (brimonidine tartrate, brinzolamide, latanoprost, timolol maleate, and pilocarpine hydrochloride) on ocular surface cells and to establish whether their toxicity is subsequent to cellular membrane destabilization. The toxicity of clinically efficient doses of pGDs was measured at different time points in a cell culture of human corneal epithelial cells using a redox indicator. pGD interaction with the plasma membrane was analyzed using a hemolysis assay and liposome electrokinetic chromatography. The capacity of pGDs to induce endoplasmic reticulum stress was investigated by immunoblotting. The toxicity assay showed that all pGDs decrease the viability of the epithelial cells to variable degrees. Early toxicity was measured for 4% pilocarpine and 0.15% brimonidine with 60% cell death at 4 hours, whereas 2% pilocarpine and 0.005% latanoprost showed almost 100% toxicity but only after 16 hours. The hemolysis assay and liposome electrokinetic chromatography experiments suggested that interaction between pGDs and lipid membranes is weak and cannot explain cell death through lysis. Immunoblotting revealed that the drugs activate endoplasmic reticulum stress and, with the exception of pilocarpine, have the capacity to induce apoptosis through upregulation of C/EBP homologous protein. Our study indicates that all studied pGDs decrease the viability of the corneal epithelial cells, but none of the tested compounds were able to destabilize cellular membranes. The pGDs seem to be internalized and can induce apoptosis through C/EBP homologous protein recruitment.

Using Postmortem hippocampi tissue can interfere with differential gene expression analysis of the epileptogenic process.

Neuropathological studies often use autopsy brain tissue as controls to evaluate changes in protein or RNA levels in several diseases. In mesial temporal lobe epilepsy (MTLE), several genes are up or down regulated throughout the epileptogenic and chronic stages of the disease. Given that postmortem changes in several gene transcripts could impact the detection of changes in case-control studies, we evaluated the effect of using autopsy specimens with different postmortem intervals (PMI) on differential gene expression of the Pilocarpine (PILO)induced Status Epilepticus (SE) of MTLE. For this, we selected six genes (Gfap, Ppia, Gad65, Gad67, Npy, and Tnf-α) whose expression patterns in the hippocampus of PILO-injected rats are well known. Initially, we compared hippocampal expression of naïve rats whose hippocampi were harvested immediately after death (0h-PMI) with those harvested at 6h postmortem interval (6h-PMI): Npy and Ppia transcripts increased and Tnf-α transcripts decreased in the 6h-PMI group (p<0.05). We then investigated if these PMI-related changes in gene expression have the potential to adulterate or mask RT-qPCR results obtained with PILO-injected rats euthanized at acute or chronic phases. In the acute group, Npy transcript was significantly higher when compared with 0h-PMI rats, whereas Ppia transcript was lower than 6h-PMI group. When we used epileptic rats (chronic group), the RT-qPCR results showed higher Tnf-α only when compared to 6h-PMI group. In conclusion, our study demonstrates that PMI influences gene transcription and can mask changes in gene transcription seen during epileptogenesis in the PILO-SE model. Thus, to avoid erroneous conclusions, we strongly recommend that researchers account for changes in postmortem gene expression in their experimental design.

USE OF PILOCARPINE 2% ASSOCIATED WITH ARTIFICIAL SALIVA FOR THE TREATMENT OF XEROSTOMIA: RANDOMIZED CLINICAL TRIAL

This work aimed to evaluate a topical presentation (mouthwash) of pilocarpine hydrochloride 2% associated with artificial saliva for the treatment of xerostomia.

The Sustained Effects on Tear Volume of Pilocarpine Hydrochloride in Gelatin by Hydrogel Administered by An Implant-mediated Drug Delivery System.

Pilocarpine hydrochloride is commonly prescribed to patients with dry mouth and eye using a frequent dosing schedule. The aim of this study was to evaluate the sustained effects of this highly soluble drug carried by a gelatin hydrogel, which was administered by an implant mediated drug delivery system (IMDDS). The IMDDS was installed in a total of 24 rabbits. After complete healing, pilocarpine hydrochloride was administered as 30 mg as raw powder (Group 1; n = 8), 30 mg in gelatin hydrogel (Group 2; n = 8), and 60 mg in gelatin hydrogel (Group 3; n = 8). The effects were evaluated by tear volume measured using the Schirmer tear test for 2 weeks after administration. All 3 groups showed an increase in tear volume from the initial measurement at 1 hour. Group 1 exhibited this increase for 24 hours, while Groups 2 and 3 sustained this increase for 5 days and 7.5 days, respectively. When provided in gelatin hydrogel, highly water-soluble pilocarpine hydrochloride administered through IMDDS resulted in sustained effects with increased tear volume in normal rabbits.

Anticonvulsant Effect of Swertiamarin Against Pilocarpine-Induced Seizures in Adult Male Mice.

Epilepsy is one of the common and major neurological disorders, approximately a third of the individuals with epilepsy suffer from seizures and not able to successfully respond to available medications. Current study was designed to investigate whether Swertiamarin (Swe) had anticonvulsant activity in the pilocarpine (PILO)-treated mice. Thirty minutes prior to the PILO (280mg/kg) injection, the mice were administrated with Swe (50, 150, and 450mg/kg) and valproate sodium (VPA, 200mg/kg) once. Seizures and electroencephalography (EEG) were observed, and then the mice were killed for Nissl, Fluoro-jade B (FJB) staining. Astrocytic activation was examined in the hippocampus. Western blot analysis was used to examine the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). The results indicated that pretreatment with Swe (150, 450mg/kg) and VPA (200mg/kg) significantly delayed the onset of the first convulsion and reduced the incidence of status epilepticus and mortality. Analysis of EEG recordings demonstrated that Swe (150, 450mg/kg) and VPA (200mg/kg) sharply decreased epileptiform discharges. Furthermore, Nissl and FJB staining revealed that Swe (150, 450mg/kg) and VPA (200mg/kg) relieved the neuronal damage. Additionally, Swe (450mg/kg) dramatically inhibited astrocytic activation. Western blot analysis showed that Swe (450mg/kg) significantly decreased the expressions of IL-1β, IL-6, TNF-α and elevated the expression of IL-10. Taken together, these findings revealed that Swe exerted anticonvulsant effects on PILO-treated mice. Further studies are encouraged to investigate these beneficial effects of Swe as an adjuvant in epilepsy.

Synthesis and evaluation of mucoadhesive acryloyl-quaternized PDMAEMA nanogels for ocular drug delivery

Poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) nanogels were synthesized via surfactant-free free-radical polymerization technique in aqueous conditions utilizing N,N’-methylene-bis-acrylamide (MBA) as a crosslinking agent. The PDMAEMA nanogels were subsequently quaternized with acryloyl chloride in order to yield mucoadhesive materials which incorporate two mucoadhesive concepts; electrostatic interactions and covalent bond forming acrylate groups. The native PDMAEMA nanogels were found to exhibit good mucoadhesive properties on ex vivo bovine conjunctival tissues, which was found to increase proportionally with the degree of quaternization. With a view to determine the ocular drug delivery capabilities of the materials, both quaternized and native nanogels were loaded with pilocarpine hydrochloride via an absorption method, and their in vitro release profiles were analysed. The nanogels were found to exhibit a high loading capacity (>20% of total weight) and a sustained release over 6h.