Co-Combination of Pregabalin and Withania coagulans-Extract-Loaded Topical Gel Alleviates Allodynia and Hyperalgesia in the Chronic Sciatic Nerve Constriction Injury for Neuropathic Pain in Animal Model

Abstract

The current study reports the fabrication of co-combination gel using Pregabalin and Withania coagulans fruit extract to validate its effectiveness for neuropathic pain in chronic constriction injury (CCI) rat models. Three topical gels were prepared using Carbopol 934 through a pseudo-ternary phase diagram incorporating the Pregabalin (2.5%), Withania coagulans extract (2%), and co-combination of both Pregabalin (2.5%) and Withania coagulans extract (2%). Gels were characterized. FTIR showed a successful polymeric network of the gel without any interaction. The drug distribution at the molecular level was confirmed by XRD. The AFM images topographically indicated the rough surface of gels with a size range from 0.25 to 330 nm. DSC showed the disappearance of sharp peaks of the drug and extract, showing successful incorporation into the polymeric network of gels. The in vitro drug release of co-combination gel was 73% over 48 h. The mechanism of drug release by combination gel was Higuchi+ fickian with values of n (0.282) and R2 (0.947). An in vivo study for pain assessment via four methods: (i) heat hyperalgesia, (ii) cold allodynia, (iii) mechano-hyperalgesia, and (iv) dynamic mechano-allodynia, confirmed that topical treatment with co-combination gel reduced the pain significantly as indicated by the p value: R1 (p < 0.001), R2 (p < 0.001), R3 (p < 0.015), and R4 (p < 0.0344). The significance order was R2 (****) > R1 (***) > R3 (**) > R4 (*) > R5 (ns).

Phytochemical composition of Lagenaria siceraria fruits from KwaZulu-Natal and Limpopo, South Africa

“…The compound Pregabalin also found in fruits of Jatropha gossypifolia L. that are utilized as newer antiepileptic drugs ( Drafor et al, 2021 ). Rural communities are always excluded due to the cost and effects of these drugs ( Asghar et al, 2022 ). However, the landrace ESC has the potential to mitigate this issue due to the financial advantage and agronomic practice required to propagate L. siceraria ( Sithole & Modi, 2015 ).…”

“…However, the landrace ESC has the potential to mitigate this issue due to the financial advantage and agronomic practice required to propagate L. siceraria ( Sithole & Modi, 2015 ). Moreover, the use of these drugs has severe consequences such as weight-gain, somnolence, dizziness, and peripheral oedema ( Asghar et al, 2022 ). However, obtaining these compounds from plants and fruits is a more natural way of maintaining good health with fewer side-effects ( Asghar et al, 2022 ).…”

Diversity in Fruit Phytochemical Composition among <em>Lagenaria siceraria</em> Landraces

“…The compound Pregabalin also found in fruits of Jatropha gossypifolia that are utilized as newer antiepileptic drugs [30]. Rural communities are always excluded due to the cost and effects of these drugs [31]. However, the landrace DSI has the potential to mitigate this issue due to the financial advantage and agronomic practice required to propagate L. siceraria [32].…”

“…However, the landrace DSI has the potential to mitigate this issue due to the financial advantage and agronomic practice required to propagate L. siceraria [32]. Moreover, the use of these drugs has severe consequences such as weight-gain, somnolence, dizziness and peripheral edema [31]. However, obtaining these compounds from plants and fruits is a more natural way of maintaining good health with fewer side-effects [31].…”

“…Moreover, the use of these drugs has severe consequences such as weight-gain, somnolence, dizziness and peripheral edema [31]. However, obtaining these compounds from plants and fruits is a more natural way of maintaining good health with fewer side-effects [31]. In addition, one of the primary causes of losses in agriculture is the deterioration of fruits post-harvest which is identified by the softening of fruits [33].…”