The conjugation of nanoparticles (NPs) with antiretroviral drugs is a drug delivery approach with great potential for managing HIV infections. Despite their promise, recent studies have highlighted the toxic effects of nanoparticles on testicular tissue and their impact on sperm morphology. This review explores the role of stereological techniques in assessing the testicular morphology in highly active antiretroviral therapy (HAART) when a nanoparticle drug delivery system is used. Also, NPs penetration and pharmacokinetics concerning the testicular tissue and blood–testis barrier form the vital part of this review. More so, various classes of NPs employed in biomedical and clinical research to deliver antiretroviral drugs were thoroughly discussed. In addition, considerations for minimizing nanoparticle‐drugs toxicity, ensuring enhanced permeability of nanoparticles, maximizing drug efficacy, ensuring adequate bioavailability, and formulation of HAART‐NPs fabrication are well discussed.

Background. The application of nanomedicine to antiretroviral drug delivery holds promise in reducing the comorbidities related to long-term systemic exposure to highly active antiretroviral therapy (HAART). However, the safety of drugs loaded with silver nanoparticles has been debatable. This study is aimed at evaluating the effects of HAART-loaded silver nanoparticles (HAART-AgNPs) on the behavioural assessment, biochemical indices, morphological, and morphometric of the hippocampus in diabetic Sprague-Dawley rats. Methods. Conjugated HAART-AgNPs were characterized using FTIR spectroscopy, UV spectrophotometer, HR-TEM, SEM, and EDX for absorbance peaks, size and morphology, and elemental components. Forty-eight male SD rats ( g) were divided into nondiabetic and diabetic groups. Each group was subdivided into ( ) A (nondiabetic+vehicle), B (nondiabetic+HAART), C (nondiabetic+HAART-AgNPs), D (diabetic+vehicle), E (diabetic+HAART), and F (diabetic+HAART-AgNPs). Morris water maze, Y-maze test, and weekly blood glucose levels were carried out. Following the last dose of 8-week treatment, the rats were anaesthetized and euthanized. Brain tissues were carefully removed and postfixed for Nissl staining histology. Results. 1.5 M concentration of HAART-AgNPs showed nanoparticle size 20.3 nm with spherical shape. HAART-AgNPs revealed 16.89% of silver and other elemental components of HAART. The diabetic control rats showed a significant increase in blood glucose, reduced spatial learning, positive hippocampal Nissl-stained cells, and a significant decrease in GSH and SOD levels. However, administration of HAART-AgNPs to diabetic rats significantly reduced blood glucose level, improved spatial learning, biochemical indices, and enhanced memory compared to diabetic control. Interestingly, diabetic HAART-AgNP-treated rats showed a significantly improved memory, increased GSH, SOD, and number of positive Nissl-stained neurons compared to diabetic-treated HAART only. Conclusion. Administration of HAART to diabetic rats aggravates the complications of diabetes and promotes neurotoxic effects on the experimental rats, while HAART-loaded silver nanoparticle (HAART-AgNP) alleviates diabetes-induced neurotoxicity.

This study investigated the toxic effects of silver on the kidneys and livers of Sprague-Dawley rats after administering multiple doses of silver nanoparticles synthesized using extracts of Cinnamomum cassia (CcAgNPs). Twenty-four Sprague-Dawley rats (250 +/- 20 g) were randomly assigned to four groups (A-D) of six animals per group and treated for 8 weeks. Group A was administered 200 mg/kg of Cinnamon Cassia extract (Cc), group B 5 mg/kg of CcAgNPs, group C 10 mg/kg of CcAgNPs, and group D normal saline. Body weight was measured weekly and fasting blood glucose was measured fortnightly. At the end of the experiment, animals were euthanized and organs (livers and kidneys) were fixed in neutral buffered formalin and processed for light microscopy (H&E). Body weight differences were significantly higher (P < 0.05) in the low-dose Cc group and the kidney to body weight ratio was not significant. Renal function analysis of proteins and ketones showed a significant increase in CcAgNP-treated rats (P < 0.05). Kidney and liver histology showed distortions in hepatocytes and sinusoidal linings with infiltrations especially in the higher dose groups. Kidney histology mirrored degenerative changes in glomerular and Bowman's capsules with fibrillary mesangial interstitium. CcAgNPs impairs renal and hepatic morphology and function after a long period of administration.

Reproductive derangement and metabolic disorders in human immunodeficiency virus (HIV) infected persons require a nanoparticle delivery system to convey antiretroviral drugs to the anatomical sanctuary such as testis. This study investigated the effects of tenofovir disoproxil fumarate (TDF) loaded silver nanoparticles (AgNPs) on the testicular oxidative stress, inflammatory cytokines and histology in male diabetic rats. Thirty-six Sprague-Dawley rats weighing 230 ± 20 g were randomly divided into diabetic and non-diabetic groups (n = 18). Diabetes was induced using the fructose-streptozotocin (Frt-STZ) rat model. Both groups were further divided into three (n = 6) and administered distilled water, TDF, or TDF-AgNP. Results obtained with the TDF-AgNP administration showed a significant increase (p < .05) in the reduced glutathione and catalase levels. Tumour necrosis factor-alpha and interleukin 6 were reduced in diabetic rats administered TDF-AgNP. More so, administration of TDF-AgNP to diabetic rats improved testicular histoarchitecture in diabetic rats. In addition, diabetic rats administered TDF-AgNP showed a significant reduction (p < .05) in blood glucose levels. TDF-AgNP to diabetic rats enhanced testicular antioxidant enzyme, reduced testicular inflammation, and alleviated structural derangements in the testis. Thus, the application of AgNP to deliver TDF may alleviate testicular toxicity and subsequently cater for neglected reproductive dysfunction during the management of HIV infection.

Tenofovir disoproxil fumarate (TDF) is the highly recommended antiretroviral drug in human immunodeficiency virus management. Although research has shown the neurological and metabolic disorders associated with TDF administration, the effect of TDF-silver nanoparticles conjugate (TDF-AgNPs) on the disorders has not been fully elucidated. Thus, this study evaluated the neuroprotective effects of TDF-AgNPs on ultrastructural and cytoarchitectonic properties of the prefrontal cortex (PFC) in diabetic rats. Forty-two adult male Sprague-Dawley rats (250 ± 13 g) were randomly divided into non-diabetic groups (1-3) and diabetic groups (4-6), each administered distilled water (0.5 ml/100g, p.o), TDF (26.8 mg/kg/bw, p.o) or TDF-AgNPs (6.7 mg/kg, i.p). After eight weeks of administration, cognitive function, oxidative injury and tissue inflammation were evaluated. Also, PFC ultrastructure was observed using transmission electron microscopy, Nissl staining and immunohistochemistry. Diabetic rats administered TDF exhibited cognitive deficits; and increases in blood glucose, malondialdehyde and interleukin-1 beta (IL-1β) levels, which correlate with decreases in glutathione level, and superoxide dismutase (SOD) and catalase activities. Furthermore, loss of PFC astrocytes and neuronal organelles was observed. Conversely, TDF-AgNPs administration to diabetic rats improved cognitive deficits; and increased glutathione, SOD, and catalase, but reduced PFC malondialdehyde and IL-1β concentrations. Notably, TDF-AgNPs prevented loss of PFC neurons and astrocytic cells, and morphology aberration of neuronal organelles. This study suggests that TDF-AgNPs attenuated cognitive deficits via silver nanoparticles' antioxidant and anti-inflammatory properties, preventing the loss of PFC astrocytes and neurons. The TDF-AgNPs may be utilized to ameliorate the neurological dysfunction caused by prolonged TDF administration.

The management of bacterial infections, especially trains of methicillin-resistant Staphylococcus aureus observe in health care settings, has markedly improved with the introduction of established drugs but using newer nano-based formulations. This study investigates the effects of vancomycin-linoleic acid nanoparticles on testicular tissue in an experimental animal model. Twenty-five adult male Sprague–Dawley rats maintained at the Animal House of the Biomedical Resources Unit were assigned to five groups namely E – solid lipid nanoparticles; F – vancomycin solid lipid nanoparticle; G – linoleic acid nanoparticle; H – vancomycin linoleic acid; and A – control. Perturbations in seminal fluid parameters showed a reduced sperm count in groups F & G which was statistically significant (p < .05) but motility and morphology were not significant when compared to controls (A). Reduced testosterone levels were found in groups E, F and H but were not statistically significant (p > .05). There was also increased luteinizing hormone (LH) and decreased in follicular stimulating hormone (FSH) levels was statistically significant (p < .05). Hypoplasia, tubular atrophy and shrinkage were observed in histologic sections of the treated groups with basement membrane thickening. Vancomycin solid lipid nanoparticle and its constituents SLN and LA disrupted testicular morphometry and the hormonal milieu sufficient to potentially induce altered reproductive function.