# Solid lipid nanoparticles enhance piracetam’s neuroprotective action in streptozotocin-induced cognitive dysfunction

**Authors:** Abhishek Mishra, Bhabani Sankar Satapathy, Pratap Kumar Sahu

PMC · DOI: 10.1186/s11671-026-04528-3 · 2026-03-29

## TL;DR

This study shows that piracetam, a drug repurposed into solid lipid nanoparticles, improves cognitive function in diabetic rats better than the drug alone.

## Contribution

The novel contribution is the development and evaluation of piracetam-loaded solid lipid nanoparticles for treating diabetes-induced cognitive dysfunction.

## Key findings

- PSLNs improved memory and behavior in diabetic rats compared to plain piracetam and controls.
- PSLNs showed higher drug retention and accumulation in the brain, as indicated by improved pharmacokinetic parameters.
- Histopathology showed restored brain tissue architecture in PSLN-treated rats.

## Abstract

Diabetes-induced cognitive dysfunction remains an unaddressed medical concern across the globe with limited options left with conventional drug therapy. Piracetam, the first identified nootropic agent has been repurposed in the current study via solid-lipid nanoparticle against streptozotocin-induced cognitive dysfunction in rats. Experimental piracetam loaded solid-lipid nanoparticles (PSLNs) were developed by conventional nanoprecipitation method and characterized in terms of SEM, AFM, DLS, zeta potential, drug loading efficiency etc. In vivo efficacy of the selected PSLNs was analysed. Various biochemical parameters were analysed along with histopathology and brain pharmacokinetic studies. Experimental PSLNs were spherical, nanosized, homogenous (PDI: 0.21 ± 0.5) with − 38.2 ± 0.3 mV surface charge. Following administration, selected PSLNs brought significant improvement in behavioural and memory function as compared to plain piracetam and control rat groups. Modulation in key enzyme/ protein expression in terms of SOD, CAT, GSH was observed in vivo in PSLNs treated rats. Histopathology of brain tissue in AD rats indicated revival of normal tissue architecture in PSLNs treated group as compared to piracetam/control groups. Key brain pharmacokinetic parameters like AUC, AUMC, MRT etc. were substantially improved for PSLNs than plain piracetam, signifying higher accumulation and retention of the drug following nanoencapsulation. However, futuristic studies are necessary to establish PSLNs as a potent modality against diabetes-induced cognitive dysfunction in clinical settings.

The online version contains supplementary material available at 10.1186/s11671-026-04528-3.

## Linked entities

- **Proteins:** SOD1 (superoxide dismutase 1), CAT (catalase), LOC23687505 (pyrimidodiazepine synthase)
- **Chemicals:** piracetam (PubChem CID 4843), streptozotocin (PubChem CID 29327)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, P4hb (prolyl 4-hydroxylase subunit beta) [NCBI Gene 25506] {aka PDI, PDIR}, Ache (acetylcholinesterase) [NCBI Gene 83817], APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}, App (amyloid beta precursor protein) [NCBI Gene 54226] {aka Abeta}, Ccnd1 (cyclin D1) [NCBI Gene 12443] {aka CycD1, Cyl-1, PRAD1, bcl-1, cD1}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 84027], Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}
- **Diseases:** necrosis (MESH:D009336), anorexia (MESH:D000855), AD (MESH:D000544), diarrhoea (MESH:D003967), seizures (MESH:D012640), inflammatory (MESH:D007249), amnesia (MESH:D000647), memory dysfunction (MESH:D008569), abnormal posture (MESH:D054972), dehydration (MESH:D003681), dementia (MESH:D003704), SL (MESH:D007863), impaired locomotion (MESH:D020233), sleeplessness (MESH:D007319), loss (MESH:D016388), neurotoxicity (MESH:D020258), Cognitive impairment (MESH:D003072), neuroinflammation (MESH:D000090862), cytotoxic (MESH:D064420), pain (MESH:D010146), behavioural abnormalities (MESH:D000014), Neurodegeneration (MESH:D019636), Diabetes (MESH:D003920), CTX (MESH:D019294), mitochondrial dysfunction (MESH:D028361), insulin resistance (MESH:D007333), neuropathological alterations (MESH:D004408), loss of body weight (MESH:D001835), type 2 diabetes (MESH:D003924), lethargy (MESH:D053609), atrophy (MESH:D001284)
- **Chemicals:** 2,2-Diphenyl-1-Picrylhydrazyl (MESH:C004931), LPS (MESH:D008070), haematoxylin (MESH:D006416), Ascorbic acid (MESH:D001205), CO2 (MESH:D002245), Nootropil (MESH:D010889), tramiprosate (MESH:C001355), HCl (MESH:D006851), nitrosourea (MESH:D009607), Saline (MESH:D012965), oxiracetam (MESH:C040619), glucose (MESH:D005947), nitrogen (MESH:D009584), formic acid (MESH:C030544), Cu (MESH:D003300), tris buffer (MESH:D014325), MTT (MESH:C070243), Nitrosamines (MESH:D009602), water (MESH:D014867), potassium persulphate (MESH:C009007), sodium nitrite (MESH:D012977), paraffin (MESH:D010232), reactive oxygen species (MESH:D017382), thiacloprid (MESH:C417209), xylazine (MESH:D014991), polyunsaturated fatty acids (MESH:D005231), memantine (MESH:D008559), phosphate (MESH:D010710), donepezil (MESH:D000077265), acetonitrile (MESH:C032159), formalin (MESH:D005557), malonaldehyde bis (dimethyl acetal) (MESH:C041295), ester (MESH:D004952), ACh (MESH:D000109), aducanumab (MESH:C000600266), GSH (MESH:D005978), blood glucose (MESH:D001786), methanol (MESH:D000432), H2O2 (MESH:D006861), sulphanilamide (MESH:D000077145), phosphoric acid (MESH:C030242), lecanemab (MESH:C000612089), dichloromethane (MESH:D008752), DMSO (MESH:D004121), PLGA (MESH:D000077182), pyrrolidine (MESH:C032519), eosin (MESH:D004801), chitosan (MESH:D048271), thiobarbituric acid (MESH:C029684), xylene (MESH:D014992), Pyrogallol (MESH:D011748), thiocholine (MESH:D013860), lipid (MESH:D008055), gold (MESH:D006046), doxorubicin (MESH:D004317), mannitol (MESH:D008353), glucosamine (MESH:D005944), TCA (MESH:D014238), EDTA (MESH:D004492), Nitrite (MESH:D009573)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** TNA2 — Rattus norvegicus (Rat), Transformed cell line (CVCL_3670), PSLN-2 — Homo sapiens (Human), Hybridoma (CVCL_9089), HT-22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321), SCC129 — Mus musculus (Mouse), Hybridoma (CVCL_J039)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13033468/full.md

---
Source: https://tomesphere.com/paper/PMC13033468