Academic Journal
View in EDS

Design and preclinical evaluation of a pH-responsive combined drug in situ gel for management of cellulitis.

Bibliographic Details
Title: Design and preclinical evaluation of a pH-responsive combined drug in situ gel for management of cellulitis.
Authors: Maiti AK; NSHM Knowledge Campus, Kolkata Group of Institutions, Kolkata, India., Mukherjee M; Bhawanipur Global Campus, Kolkata, India., Datta A; Bhawanipur Global Campus, Kolkata, India. Electronic address: adatta75@gmail.com., Bhakta P; Bhawanipur Global Campus, Kolkata, India.
Source: International journal of pharmaceutics [Int J Pharm] 2026 Oct 05; Vol. 703, pp. 127371. Date of Electronic Publication: 2026 Sep 02.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7804127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3476 (Electronic) Linking ISSN: 03785173 NLM ISO Abbreviation: Int J Pharm Subsets: MEDLINE
Imprint Name(s): Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
MeSH Terms: Cellulitis*/drug therapy , Cellulitis*/microbiology , Anti-Bacterial Agents*/administration & dosage , Anti-Bacterial Agents*/chemistry , Anti-Bacterial Agents*/pharmacology , Ofloxacin*/administration & dosage , Ofloxacin*/chemistry , Ofloxacin*/pharmacokinetics , Ofloxacin*/pharmacology , Lidocaine*/administration & dosage , Lidocaine*/chemistry, Nanoparticles/chemistry ; Nanoparticles/administration & dosage ; Staphylococcus aureus/drug effects ; Animals ; Hydrogen-Ion Concentration ; Gels ; Drug Liberation ; Male ; Delayed-Action Preparations ; Rats, Sprague-Dawley ; Rats ; Particle Size
Abstract: Global disease patterns are being rapidly reshaped by environmental changes such as rising temperatures, pollution, and more frequent natural disasters. Notable effects include a rise in skin infections, such as cellulitis, as well as upper respiratory and urinary tract infections. Cellulitis, an acute bacterial infection predominantly caused by S. aureus and Streptococcus species, is clinically challenging due to recurrence, primarily because of antimicrobial resistance and limitations of standard systemic therapies. Oral antibiotics like ofloxacin, though effective, are associated with significant suboptimal drug localization, systemic adverse effects and necessitate reliable and more targeted therapeutic approaches. This study reports the development and optimization of a pH-sensitive nanoparticle-loaded in situ gel for the local management of cellulitis. As the encapsulating polymer, Eudragit® S100 was used to load Ofloxacin via the nanoprecipitation method and optimized through Design of Experiments, achieving high entrapment efficiency of ∼96% and a nano size of 85-110 nm. These nanoparticles were incorporated into a Carbopol-HPMC-based in situ gel containing lidocaine to provide immediate pain-relieving action. The system exhibited pH-triggered sol-gel transition, enhanced viscosity under simulated wound conditions, and sustained drug release following controlled kinetics. In vitro and ex vivo studies demonstrated prolonged drug release post permeation, effective antimicrobial activity driven by MIC and MBC tests, and improved retention. In vivo evaluation in S. aureus-infected rat models confirmed reduced lesion severity, absence of skin irritation, inflammation and accelerated healing. Overall, this dual-delivery platform renders a promising scheme for concurrent pain management and sustained antimicrobial therapy, potentially improving patient compliance by altering therapeutic outcomes in cellulitis treatment.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Cellulitis; In situ gel; Ofloxacin; Sustained antimicrobial therapy; pH-responsive drug delivery
Substance Nomenclature: 0 (Gels)
0 (Anti-Bacterial Agents)
A4P49JAZ9H (Ofloxacin)
98PI200987 (Lidocaine)
0 (Delayed-Action Preparations)
Entry Date(s): Date Created: 20260902 Date Completed: 20260919 Latest Revision: 20260919
Update Code: 20260920
DOI: 10.1016/j.ijpharm.2026.127371
PMID: 42685878
Database: MEDLINE
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://www.doi.org/10.1016/j.ijpharm.2026.127371?
    Name: ScienceDirect (all content) (s7799221)
    Category: fullText
    Text: View record from ScienceDirect
    MouseOverText: View record from ScienceDirect
  – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:cmedm&genre=article&issn=18733476&ISBN=&volume=703&issue=&date=20261005&spage=127371&pages=127371&title=International journal of pharmaceutics&atitle=Design%20and%20preclinical%20evaluation%20of%20a%20pH-responsive%20combined%20drug%20in%20situ%20gel%20for%20management%20of%20cellulitis.&aulast=Maiti%20AK&id=DOI:10.1016/j.ijpharm.2026.127371
    Name: Full Text Finder (for New FTF UI) (ns324271)
    Category: fullText
    Text: Full Text Finder
    MouseOverText: Full Text Finder
Header DbId: cmedm
DbLabel: MEDLINE
An: 42685878
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Design and preclinical evaluation of a pH-responsive combined drug in situ gel for management of cellulitis.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Maiti+AK%22">Maiti AK</searchLink>; NSHM Knowledge Campus, Kolkata Group of Institutions, Kolkata, India.<br /><searchLink fieldCode="AU" term="%22Mukherjee+M%22">Mukherjee M</searchLink>; Bhawanipur Global Campus, Kolkata, India.<br /><searchLink fieldCode="AU" term="%22Datta+A%22">Datta A</searchLink>; Bhawanipur Global Campus, Kolkata, India. Electronic address: adatta75@gmail.com.<br /><searchLink fieldCode="AU" term="%22Bhakta+P%22">Bhakta P</searchLink>; Bhawanipur Global Campus, Kolkata, India.
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%227804127%22">International journal of pharmaceutics</searchLink> [Int J Pharm] 2026 Oct 05; Vol. 703, pp. 127371. <i>Date of Electronic Publication: </i>2026 Sep 02.
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Elsevier%2FNorth-Holland+Biomedical+Press%22">Elsevier/North-Holland Biomedical Press </searchLink><i>Country of Publication: </i>Netherlands <i>NLM ID: </i>7804127 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1873-3476 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2203785173%22">03785173 </searchLink><i>NLM ISO Abbreviation: </i>Int J Pharm <i>Subsets: </i>MEDLINE
– Name: PublisherInfo
  Label: Imprint Name(s)
  Group: PubInfo
  Data: <i>Original Publication</i>: Amsterdam, Elsevier/North-Holland Biomedical Press.
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22Cellulitis%22">Cellulitis*</searchLink>/<searchLink fieldCode="MM" term="%22Cellulitis+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Cellulitis%22">Cellulitis*</searchLink>/<searchLink fieldCode="MM" term="%22Cellulitis+microbiology%22">microbiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Anti-Bacterial+Agents%22">Anti-Bacterial Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Anti-Bacterial+Agents+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Anti-Bacterial+Agents%22">Anti-Bacterial Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Anti-Bacterial+Agents+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Anti-Bacterial+Agents%22">Anti-Bacterial Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Anti-Bacterial+Agents+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Ofloxacin%22">Ofloxacin*</searchLink>/<searchLink fieldCode="MM" term="%22Ofloxacin+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Ofloxacin%22">Ofloxacin*</searchLink>/<searchLink fieldCode="MM" term="%22Ofloxacin+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Ofloxacin%22">Ofloxacin*</searchLink>/<searchLink fieldCode="MM" term="%22Ofloxacin+pharmacokinetics%22">pharmacokinetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Ofloxacin%22">Ofloxacin*</searchLink>/<searchLink fieldCode="MM" term="%22Ofloxacin+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Lidocaine%22">Lidocaine*</searchLink>/<searchLink fieldCode="MM" term="%22Lidocaine+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Lidocaine%22">Lidocaine*</searchLink>/<searchLink fieldCode="MM" term="%22Lidocaine+chemistry%22">chemistry</searchLink><br /><searchLink fieldCode="MH" term="%22Nanoparticles%22">Nanoparticles</searchLink>/<searchLink fieldCode="MH" term="%22Nanoparticles+chemistry%22">chemistry</searchLink> ; <searchLink fieldCode="MH" term="%22Nanoparticles%22">Nanoparticles</searchLink>/<searchLink fieldCode="MH" term="%22Nanoparticles+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Staphylococcus+aureus%22">Staphylococcus aureus</searchLink>/<searchLink fieldCode="MH" term="%22Staphylococcus+aureus+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Hydrogen-Ion+Concentration%22">Hydrogen-Ion Concentration</searchLink> ; <searchLink fieldCode="MH" term="%22Gels%22">Gels</searchLink> ; <searchLink fieldCode="MH" term="%22Drug+Liberation%22">Drug Liberation</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Delayed-Action+Preparations%22">Delayed-Action Preparations</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%2C+Sprague-Dawley%22">Rats, Sprague-Dawley</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%22">Rats</searchLink> ; <searchLink fieldCode="MH" term="%22Particle+Size%22">Particle Size</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Global disease patterns are being rapidly reshaped by environmental changes such as rising temperatures, pollution, and more frequent natural disasters. Notable effects include a rise in skin infections, such as cellulitis, as well as upper respiratory and urinary tract infections. Cellulitis, an acute bacterial infection predominantly caused by S. aureus and Streptococcus species, is clinically challenging due to recurrence, primarily because of antimicrobial resistance and limitations of standard systemic therapies. Oral antibiotics like ofloxacin, though effective, are associated with significant suboptimal drug localization, systemic adverse effects and necessitate reliable and more targeted therapeutic approaches. This study reports the development and optimization of a pH-sensitive nanoparticle-loaded in situ gel for the local management of cellulitis. As the encapsulating polymer, Eudragit® S100 was used to load Ofloxacin via the nanoprecipitation method and optimized through Design of Experiments, achieving high entrapment efficiency of ∼96% and a nano size of 85-110 nm. These nanoparticles were incorporated into a Carbopol-HPMC-based in situ gel containing lidocaine to provide immediate pain-relieving action. The system exhibited pH-triggered sol-gel transition, enhanced viscosity under simulated wound conditions, and sustained drug release following controlled kinetics. In vitro and ex vivo studies demonstrated prolonged drug release post permeation, effective antimicrobial activity driven by MIC and MBC tests, and improved retention. In vivo evaluation in S. aureus-infected rat models confirmed reduced lesion severity, absence of skin irritation, inflammation and accelerated healing. Overall, this dual-delivery platform renders a promising scheme for concurrent pain management and sustained antimicrobial therapy, potentially improving patient compliance by altering therapeutic outcomes in cellulitis treatment.<br /> (Copyright © 2026 Elsevier B.V. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Cellulitis; In situ gel; Ofloxacin; Sustained antimicrobial therapy; pH-responsive drug delivery
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Gels)<br />0 (Anti-Bacterial Agents)<br />A4P49JAZ9H (Ofloxacin)<br />98PI200987 (Lidocaine)<br />0 (Delayed-Action Preparations)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260902 <i>Date Completed: </i>20260919 <i>Latest Revision: </i>20260919
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260920
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1016/j.ijpharm.2026.127371
– Name: AN
  Label: PMID
  Group: ID
  Data: 42685878
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42685878
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.ijpharm.2026.127371
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 127371
    Subjects:
      – SubjectFull: Nanoparticles chemistry
        Type: general
      – SubjectFull: Nanoparticles administration & dosage
        Type: general
      – SubjectFull: Staphylococcus aureus drug effects
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Hydrogen-Ion Concentration
        Type: general
      – SubjectFull: Gels
        Type: general
      – SubjectFull: Drug Liberation
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Delayed-Action Preparations
        Type: general
      – SubjectFull: Rats, Sprague-Dawley
        Type: general
      – SubjectFull: Rats
        Type: general
      – SubjectFull: Particle Size
        Type: general
      – SubjectFull: Cellulitis drug therapy
        Type: general
      – SubjectFull: Cellulitis microbiology
        Type: general
      – SubjectFull: Anti-Bacterial Agents administration & dosage
        Type: general
      – SubjectFull: Anti-Bacterial Agents chemistry
        Type: general
      – SubjectFull: Anti-Bacterial Agents pharmacology
        Type: general
      – SubjectFull: Ofloxacin administration & dosage
        Type: general
      – SubjectFull: Ofloxacin chemistry
        Type: general
      – SubjectFull: Ofloxacin pharmacokinetics
        Type: general
      – SubjectFull: Ofloxacin pharmacology
        Type: general
      – SubjectFull: Lidocaine administration & dosage
        Type: general
      – SubjectFull: Lidocaine chemistry
        Type: general
    Titles:
      – TitleFull: Design and preclinical evaluation of a pH-responsive combined drug in situ gel for management of cellulitis.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Maiti AK
      – PersonEntity:
          Name:
            NameFull: Mukherjee M
      – PersonEntity:
          Name:
            NameFull: Datta A
      – PersonEntity:
          Name:
            NameFull: Bhakta P
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 05
              M: 10
              Text: 2026 Oct 05
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1873-3476
          Numbering:
            – Type: volume
              Value: 703
          Titles:
            – TitleFull: International journal of pharmaceutics
              Type: main
ResultId 1