Formulation Optimization and Characterization of Tizanidine Hydrochloride-Loaded Gold Nanoparticles Using Quality by Design Approach.

BACKGROUND: Gold nanoparticles (GNP) have been used extensively in cancer biologics and as drug carrier systems for improved pharmacokinetics and effective therapeutic action. GNPs also ensure reliable diagnosis with sensitive imaging. OBJECTIVE: This study aimed to synthesize tizanidine hydrochloride (TZN)-biodegradable gold (Au) nanoparticles by the reduction of chloroauric acid (HAuCl4) with trisodium citrate using a microwave synthesizer and quality by design approach. METHODS: The formulation method used was optimized using a 32 (two-factor, three-level design) factorial experiment. Temperature (X1) and concentration of gold salt (X2) were the two independent factors, and particle size (Y1), Percent drug entrapment efficiency (Y2), and polydispersity index (Y3) were the responses recorded for the study. RESULT: The results of the study revealed that the optimized nanoparticles (TGN8) had a particle size (Y1) of 195 ± 1.2 nm, a polydispersity index of 0.2, and entrapment efficiency of 99.0 ± 2.9% at an optimized concentration of 14 mM gold salt (X1) and 100 0C temperature (X2). Atomic Force Microscopy showed the spherical shape particles. In vitro drug release was found to be 62.1 ± 0.5% release of TZN in simulated gastric buffer (pH 1.2) and 45.5 ± 2.8% in physiological buffer (pH 7.4). CONCLUSION: Overall, the study identified the optimal formulation conditions for TZN GNPs by considering the effects of independent variables on desired responses.

Infectious causes of acute encephalitis syndrome hospitalizations in Central India, 2018-20.

BACKGROUND: We enhanced surveillance of hospitalizations of all ages for acute encephalitis syndrome (AES) along with infectious aetiologies, including the Japanese encephalitis virus (JEV). METHODS: From October 2018 to September 2020, we screened neurological patients for AES in all age groups in Maharashtra and Telangana States. AES cases were enrolled at study hospitals along with other referrals and sampled with cerebrospinal fluid, acute and convalescent sera. We tested specimens for non-viral aetiologies viz. leptospirosis, typhoid, scrub typhus, malaria and acute bacterial meningitis, along with viruses - JEV, Dengue virus (DENV), Chikungunya virus (CHIKV), Chandipura virus (CHPV) and Herpes simplex virus (HSV). RESULTS: Among 4977 neurological hospitalizations at three study site hospitals over two years period, 857 (17.2%) were AES. However, only 287 (33.5%) AES cases were eligible. Among 278 (96.9%) enrolled AES cases, infectious aetiologies were identified in 115 (41.4%) cases, including non-viral in 17 (6.1%) cases - leptospirosis (8), scrub-typhus (3) and typhoid (6); and viral in 98 (35.3%) cases - JEV (58, 20.9%), HSV (22, 7.9%), DENV (15, 5.4%) and CHPV (3, 1.1%). JEV confirmation was significantly higher in enrolled cases than referred cases (10.2%) (p < 0.05). However, the contribution of JEV in AES cases was similar in both children and adults. JE was reported year-round and from adjacent non-endemic districts. CONCLUSIONS: The Japanese encephalitis virus continues to be the leading cause of acute encephalitis syndrome in central India despite vaccination among children. Surveillance needs to be strengthened along with advanced diagnostic testing for assessing the impact of vaccination.

Formulation Optimization and Biopharmaceutical Evaluation of Imatinib Mesylate Loaded ß-cyclodextrin Nanosponges.

BACKGROUND: Many researchers have prepared and evaluated nanosponges and claimed their advantages as an effective drug carrier, especially it was observed prominently in case of anti-fungal drugs. The materials employed to synthesize nanosponges were mainly crosslinking agents, different beta-cyclodextrin and other cellulose-based polymers. Many of them had used ratio proportions of cross-linking agents, d polymers to synthesize these nanosponges which ultimately produce a porous mesh-like network known as nanosponges where actually drug is encapsulated or loaded. OBJECTIVE: In the present investigation, we observed the effect of various levels of crosslinking agents and beta-cyclodextrin concentrations on porosity, drug encapsulation, zeta potential and drug release by employing the quality by design approach to synthesize nanosponges rather than merely keeping both concentrations in proportions. METHODS: We have slightly modified the method reported earlier i.e. melting method in which we have used rota evaporator receiver vessel for melting cross-linking agent and beta- cyclodextrin, rotated at 20 RPM at 100°C. RESULTS: In a quality by design approach, we observed that out of four dependent variables i.e. porosity, drug loading, zeta potential and drug release, three significantly depend on the crosslinking of beta-cyclodextrin molecules which is highly appreciated by the amount of cross-linking agent present in the reaction. The pharmacokinetics of Imatinib loaded optimized nanosponges were compared with the reference product to observe the pattern of absorption and disposition. CONCLUSION: Nanosponges synthesized by optimization technique could be effective means of anti-cancer drug oral administration as they encapsulate the drug effectively and offer a prolonged release of drug which gradually releases the drug and avoids unnecessary exposure of the drug.

Cerebral malaria in rural India.

OBJECTIVE: A cross-sectional hospital based study was carried out to investigate clinical features and outcome of cerebral malaria in a rural area. METHODS: All children fulfilling inclusion criteria, were enrolled and were entered on specially designed proforma. Their peripheral smear (PS) were studied based on which the diagnosis was classified as definite cerebral malaria (DCM) and probable cerebral malaria (PCM). RESULT: There were 2991 admissions in pediatric ward, of which 1394 (46.6%) were for fever. Of 781 (56.6%) cases with fever no cause was identified. Of the 56 cases positive for malarial parasite on PS 4.3% were Plasmodium vivax (PV) and 2.8% Plasmodium falciparum (PF). Fifteen patients fulfilled the criteria for study of which 7 were DCM and 8 belonged to PCM group. Twelve (80%) were in school-going age group and M : F ratio was 2 : 1. All patients presented with fever, and CNS involvement, 66.6% had convulsion, 7 developed coma, anaemia was seen in 60%, but only 20% required blood transfusion. Splenomegaly and hepatomegaly was seen in 53.3% and 47% cases respectively. Two patients died, one each in DCM and PCM. Cerebral malaria is a serious complication of severe falciparum malaria and is seen in approximately 32% of PF positive cases. CONCLUSION: PCM is an entity which should be kept in mind when treating fever without definite focus in rural areas, because timely and specific therapy is lifesaving.