Pharmacokinetics and Pharmacodynamics of a Nanostructured Lipid Carrier Co-Encapsulating Artemether and miRNA for Mitigating Cerebral Malaria.

Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood-brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.

Antifungal Resistance of Candida Species Isolated from HIV Patients in a Tertiary Care Hospital, Mysuru, Karnataka.

CONTEXT: Candidiasis still remains as a common opportunistic infection in patients with human immunodeficiency virus (HIV). Drug resistance has become a serious health concern because of indiscriminate usage and dosage. AIM: To determine the antifungal resistance pattern of Candida albicans and non-albicans Candida (NAC) from HIV patients. SUBJECTS AND METHODS: The study was carried out in the department of microbiology at a tertiary care hospital. Candida isolates obtained from HIV patients were tested for drug susceptibility by Vitek-2 automated system. RESULTS: Antifungal susceptibility pattern (n=109) revealed that 15% of the isolates were resistant to at-least one and 85% were sensitive to all the drugs tested. About 10% and 19% of C. albicans showed resistance to fluconazole and flucytosine respectively. Among non-albicans tested, only C. tropicalis (14%) exhibited resistance to flucytosine. CONCLUSIONS: Knowledge on epidemiology, species prevalence, and drug resistance pattern may guide for effective therapy. This reduces morbidity and also improves the quality of life.

Drug resistance pattern of mycobacterial isolates in HIV and non-HIV population in South India.

BACKGROUND: Emergence of drug resistance has complicated the treatment of tuberculosis (TB). WHO reports India to be one among 27 "high burden" multidrug-resistant (MDR) TB countries. OBJECTIVE: To diagnose TB and detect drug resistance of mycobacterial isolates in acid-fast bacilli (AFB) smear negative HIV reactive patients (Group A) and compare them with HIV seropositive AFB smear positive (Group B) and HIV-seronegative AFB positive cases (Group C). MATERIALS AND METHODS: Clinical specimens collected in all groups were processed as per the standard protocol except blood, which was processed by lysis centrifugation technique. They were then inoculated with Lowenstein-Jensen media and the isolates obtained were subjected to drug susceptibility test (DST) by proportion method and genotype MTBDR plus assay. RESULTS: In Group A, 162 patients were included. Of the 443 clinical samples collected, 76 mycobacterial strains were obtained from 67 (41%) patients. Of these, 50 (65.8%) were sensitive to all drugs and 26 (34.2%) resistant to one or more anti-tubercular drugs. Antibiogram of Group A when compared with Group B and C showed that the MDR rate 6.6%, 6.7% and 8% respectively) did not differ much; but resistance to at least single drug was (26 [34.2%], 3 [10%], and 8 [16%]), respectively. CONCLUSION: Our study suggests that HIV has no influence on the anti-tubercular resistance pattern, but increased MDR rate along with HIV in high TB burden setting stresses the need for early diagnosis and DST in providing proper regimens and improve prognosis.